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1.
Chemosphere ; 240: 124936, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31568941

RESUMO

Triphenyltin (TPT) is widely used and commonly found in a water environment, so its effects on aquatic systems are of great concern. This study aimed to reveal the effects of chronic parental exposure of TPT on thyroid disruption and growth inhibition in zebrafish. Adult zebrafish (F0 generation) were exposed to environmentally relevant concentrations (1, 10, and 100 ng/L) of TPT for 60 days, and the larvae (F1 generation) were tested without TPT treatment. Results demonstrated that parental exposure to TPT disrupts thyroid function in zebrafish offspring: serum thyroxine (T4) significantly decreased, while serum 3,5,3'-triiodothyronine (T3) increased, and several genes involved in the hypothalamic-pituitary-thyroid (HPT) axis were down-regulated. In addition, we observed developmental abnormalities in the larvae, demonstrated by a significantly altered hatching rate, malformation rate, body length, heart rate, and survival rate, as well as down-regulation of genes involved in the growth hormone/insulin-like growth factor (GH/IGF) axis. Therefore, parental exposure to TPT induces toxicity in fish offspring through perturbation of the HPT and GH/IGF axes.


Assuntos
Larva/crescimento & desenvolvimento , Compostos Orgânicos de Estanho/toxicidade , Praguicidas/toxicidade , Glândula Tireoide/patologia , Poluentes Químicos da Água/toxicidade , Animais , Feminino , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Larva/efeitos dos fármacos , Masculino , Exposição Materna/efeitos adversos , Exposição Paterna/efeitos adversos , Somatomedinas/genética , Somatomedinas/metabolismo , Glândula Tireoide/efeitos dos fármacos , Tiroxina/sangue , Tri-Iodotironina/sangue , Peixe-Zebra/embriologia
2.
J Dairy Sci ; 102(9): 8513-8526, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31255268

RESUMO

Intensive milk feeding and butyrate supplementation in calves stimulate body growth and affect gastrointestinal development. The aim of the present study was to investigate the synergistic effects of ad libitum milk replacer (MR) feeding and butyrate supplementation of MR on rumen and small intestinal growth and on gene expression in the small intestine related to growth and energy metabolism at weaning. Male Holstein calves (n = 32) received colostrum from birth to d 3 of age and MR either ad libitum (Adl) or restrictively (Res; 6 L of MR/d; 12.5% solids) with (AdlB+, ResB+) or without (AdlB-, ResB-) 0.24% butyrate from d 4 until wk 8 of age. From wk 9 to 10, all calves were weaned and were fed 2 L/d until the end of the trial. Concentrate, hay, and water were freely available. At d 80, calves were slaughtered, volatile fatty acids were measured in rumen fluid, and rumen and small intestine samples were taken for histomorphometric measurements. The expression of mRNA associated with the local insulin-like growth factor (IGF) system and glucose metabolism as well as lactase and maltase activities were measured in the intestinal mucosa. The small intestine was 3 m longer in Adl than in Res. In the atrium ruminis, papilla width was greater in Res than in Adl. Villus circumference, cut surface, and height in the duodenum, proximal jejunum, and ileum were greater in Adl than in Res and in the proximal, mid, and distal jejunum and ileum were greater in calves treated with butyrate. Crypt depth in the duodenum and proximal jejunum was greater in Adl than in Res and in the ileum was smaller in calves treated with butyrate. The villus height:crypt depth ratio was greatest in AdlB+ calves. In the proximal and mid jejunum, IGF1 mRNA abundance was lower in calves treated with butyrate. In the proximal jejunum, INSR mRNA abundance was greater in Res than in Adl. The abundance of PCK2 mRNA was greater in Res than in Adl in the duodenum and was greatest in ResB- in the mid jejunum. Lactase activity tended to be greater in Res than in Adl and after butyrate treatment in the proximal jejunum. The results indicated an elevated growth of the small intestinal mucosa at weaning due to intensive milk feeding and butyrate supplementation, and the local IGF system was involved in intestinal growth regulation. Rumen development was not affected by butyrate supplementation of MR and was slightly delayed due to ad libitum MR feeding.


Assuntos
Butiratos/administração & dosagem , Bovinos/crescimento & desenvolvimento , Dieta/veterinária , Trato Gastrointestinal/crescimento & desenvolvimento , Substitutos do Leite/administração & dosagem , Rúmen/crescimento & desenvolvimento , Animais , Colostro , Suplementos Nutricionais , Ácidos Graxos Voláteis/análise , Feminino , Trato Gastrointestinal/química , Fator de Crescimento Insulin-Like I , Lactase/metabolismo , Masculino , Leite/metabolismo , Gravidez , RNA Mensageiro/análise , Proteínas Recombinantes , Rúmen/química , Somatomedinas/genética , Desmame
3.
Sci Data ; 6: 190024, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30778253

RESUMO

As a novel IGF system member, igf3 plays an important role in gonadal development of teleost fish. Although studies have reported the unusual expression of igf3 in fish gonad, whether the igf3 affects the expression of long noncoding RNAs (lncRNAs) in gonad remains unknown. In this study, an igf3 knockdown common carp (Cyprinus carpio) model was established by RNA interference. Then RNA sequencing of C. carpio gonad after igf3 knockdown was performed. A total of 327,169,410 and 306,305,018 clean reads were identified from control and igf3-dsRNA interference group, respectively. After a stringent filtering, RNA-seq yielded 14199 lncRNA and 106932 mRNA transcripts with 124 and 353 differentially expressed lncRNAs and mRNAs. Our dataset provides an extensive resource for understanding the potential regulatory molecular mechanism of igf3 in early stage of gonadal development in C. carpio.


Assuntos
Carpas , Perfilação da Expressão Gênica , RNA Longo não Codificante , RNA Mensageiro , Somatomedinas/genética , Animais , Carpas/genética , Carpas/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Interferência de RNA , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Somatomedinas/metabolismo , Transcriptoma
4.
Physiol Biochem Zool ; 92(2): 211-222, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30735088

RESUMO

In social groups, dominant animals typically are larger and have better access to resources than subordinates. When subordinates are given the opportunity to ascend to a dominant position, they will elevate their rates of growth to help secure dominance. This study investigated the physiological mechanisms facilitating this increased growth. Using the group-living cichlid, Neolamprologus pulcher, we investigated whether the insulin-like growth factor (IGF) system-a key regulator of growth-is involved in the regulation of growth during social ascension. We also assessed differences in energy storage and expenditure among dominant, subordinate, and ascending males to determine the energetic costs associated with ascension. Daily growth rates tripled during ascension, and ascending males expended more energy after ascension, owing to higher rates of energetically costly social behaviors, increased locomotor activity, and larger home ranges. Ascenders did not increase food intake to offset increasing energetic costs but had half the liver glycogen energy stores of subordinates. Together, these results indicate a reliance on stockpiled energy reserves to fuel the high energetic demands associated with ascension. Transcript abundance of IGF binding proteins 1 (igfbp1) and 2a (igfbp2a) were low in ascenders relative to subordinates, suggesting a higher capacity for growth during ascension through increased bioavailability of circulating IGF-1. Our findings provide clear evidence of the energetic costs of social ascension and offer novel insight into the physiological mechanisms modulating the social regulation of growth.


Assuntos
Ciclídeos/crescimento & desenvolvimento , Predomínio Social , Animais , Metabolismo Energético , Regulação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Glicogênio/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Masculino , Somatomedinas/genética , Somatomedinas/metabolismo
5.
Fish Physiol Biochem ; 45(3): 955-964, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30610408

RESUMO

Accumulating evidence suggests that the growth hormone (GH)/insulin-like growth factor (IGF) system participates in fish reproduction. To understand the physiological functions of the GH/IGF system, the mRNA expression profiles of all known members of the GH/IGF system, including hepatic and ovarian gh, GH receptor (ghr), IGFs (igf-i, igf-ii), IGF-I receptor (igf-ir) and IGF binding protein (igfbp1, igfbp2), pituitary gh, and hepatic vitellogenin (vtg) were investigated during ovarian development in turbot Scophthalmus maximus. Results showed that ghr, igf-i, igf-ii, igf-ir, and igfbp2 were expressed in the liver and ovary, whereas igfbp1 and gh were undetected. The hepatosomatic index (HSI) and gonadosomatic index (GSI) gradually increased and peaked during the late vitellogenesis (Latvtg) and migratory nucleus (Mig-nucl) stages, respectively. The mRNA expression profiles of ovarian ghr, igf-ii, hepatic igf-ir, vtg, and pituitary gh were similar to the HSI; ovarian igf-i and igf-ir expression was close to the GSI. However, the hepatic mRNA levels of ghr, igf-i, and igf-ii peaked at the early vitellogenesis (Evtg) stage, and then drastically declined during ovarian development. The mRNA expression of hepatic igfbp2 decreased and reached the lowest at the atresia (Atre) stage, whereas that of ovarian igfbp2 increased and peaked at Latvtg stage. Furthermore, significant correlations between pituitary gh, ovarian ghr, igf-i, and igf-ii, and hepatic ghr, igf-i, igf-ir, and igf-ii were observed, respectively. These results suggest that GH/IGF members appear to play distinct roles in the regulation of ovarian development in turbot and will be valuable for fish reproduction and broodstock management of aqua-cultured fish species.


Assuntos
Linguados/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Hormônio do Crescimento/metabolismo , Ovário/crescimento & desenvolvimento , Somatomedinas/metabolismo , Animais , Feminino , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Linguados/metabolismo , Hormônio do Crescimento/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Somatomedinas/genética , Transcriptoma
6.
Minerva Endocrinol ; 44(1): 43-57, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29963827

RESUMO

INTRODUCTION: The different presentation of adrenocortical tumors in benign adenoma (ACA) or adrenocortical carcinoma (ACC) is related to the variability at the molecular level. The insulin-like growth factor (IGF) system is one of the most frequently altered pathways in ACC. In this review we will critically analyze the evidence regarding the pathogenic role of the IGF system in adrenal tumorigenesis, focusing on ACC. We will also examine the preclinical and clinical studies which investigated the targeting of the IGF system as a therapeutic approach in ACC. EVIDENCE ACQUISITION: The IGF system plays a crucial role in the embryogenesis of adrenal glands. No significant alterations of the IGF system were observed in ACA. In ACC, the IGF2 overexpression is one of the most frequent molecular change presented in more than 85% of cases. However, IGF2 seems to be only a tumor progression factor which requires additional hits to trigger adrenal tumorigenesis. Also, the IGF1 receptor (IGF1R) appears to be higher expressed in ACC. Many IGF1R target-drugs have been developed to inhibit the activation of the IGF system. EVIDENCE SYNTHESIS: Preclinical studies using antibody or tyrosine kinase which target the IGF1R, or the dual-targeting of IGF1R and insulin receptor (IR) reduced ACC cells proliferation both in vitro and in vivo in mouse xenograft model. However, these promising results were not confirmed in clinical trials. CONCLUSIONS: Nowadays, predictive markers for the response of target-IGF therapy are missing and further studies which investigate new molecular markers and evaluate the entire IGF receptors, including the IR, are urgently needed.


Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Somatomedinas/metabolismo , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/fisiopatologia , Biomarcadores , Regulação Neoplásica da Expressão Gênica , Humanos , Transdução de Sinais , Somatomedinas/genética
7.
Fish Physiol Biochem ; 45(1): 375-390, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30225751

RESUMO

In this study, to understand the role of the insulin-like growth factor (IGF) system in the regulation of early development in yellowtail kingfish (YTK, Seriola lalandi), an economically important marine fish species with a high potential for aquaculture, we first cloned the full-length cDNAs for igf1 and igf2 from the liver. YTK igf1 cDNA was 1946 base pairs (bp) in length with an open reading frame (ORF) of 558 bp encoding preproIGF1 of 185 amino acids (aa). The preproIGF1 consisted of 44 aa for the signal peptide, 68 aa for the mature peptide comprising B, C, A, and D domains, and 73 aa for the E domain. YTK igf2 cDNA had an ORF of 648 bp that encoded a total of 215 aa spanning the signal peptide (47 aa), the mature peptide (70 aa), and the E domain (98 aa). At the protein level, both YTK IGF1 and IGF2 exhibited high sequence identities with their corresponding fish counterparts, respectively. Subsequently, quantitative RT-PCR analysis indicated that the highest level of igf1 mRNA expression was recorded in the gonad and liver, while the igf2 mRNA expression was most abundant in the gill and liver. In addition, both igf1 and igf2 were detected in all stages of embryonic development and exhibited different gene expression patterns, supporting that IGF1 and IGF2 could be functional and play important roles during YTK embryogenesis. Overall, this initial study of IGF1 and IGF2 provides an insight into the endocrine mechanism involved in the early development of yellowtail kingfish.


Assuntos
Peixes/embriologia , Peixes/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Somatomedinas/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Embrião não Mamífero , Desenvolvimento Embrionário , Somatomedinas/genética
8.
Artigo em Inglês | MEDLINE | ID: mdl-30315898

RESUMO

DNA methylation is susceptible to various environmental factors such as salinity, temperature and nutritional conditions, and can affect gene function, organ metabolism, body growth and development. In order to explore the effect of starvation on growth-related genes in large yellow croaker (Larimichthys crocea), we studied methylation of the global DNA and growth-related genes (MSTN1,MSTN2,IGF1,IGF2) and the corresponding mRNA expressions, using ELISA-based technique, bisulfite sequencing PCR (BSP) technique and quantitative Real-time PCR (qRT-PCR) respectively. The results showed that the global DNA methylation levels were significantly different (p <0.05) between the experimental group and the control group at starvation 14d, 21d in muscle and at starvation 7d, 14d, 28d, and re-feeding 7d in liver. The CpG islands of MSTN1, MSTN2, IGF1 and IGF2 were enriched in exons rather than promoters. The proximal promoter of MSTN1 and IGF1 and the exon1 of MSTN2 had almost no methylation at all treatment stages. The methylation status in MSTN1 exon 1 and IGF2 exon 2 varied from different starvation time, and started to have significant differences on starvation 7d (p <0.05) both in liver and muscle. In the liver there was a strong positive correlation between IGF2 exon 2 methylation and global DNA methylation (r = 0.7558). The mRNA expression levels of these growth-related genes were significantly different at starvation 14d (p <0.05), but did not have significant correlation with the methylation of these exons. The results implied that exon methylation of these growth-related genes might affect post-transcriptional process.


Assuntos
Metilação de DNA , Regulação da Expressão Gênica no Desenvolvimento , Fígado/metabolismo , Músculo Esquelético/metabolismo , Perciformes/fisiologia , Inanição/veterinária , Fenômenos Fisiológicos da Nutrição Animal , Animais , Aquicultura , China , Ilhas de CpG , Éxons , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Fígado/crescimento & desenvolvimento , Músculo Esquelético/crescimento & desenvolvimento , Miostatina/genética , Miostatina/metabolismo , Especificidade de Órgãos , Perciformes/crescimento & desenvolvimento , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Distribuição Aleatória , Somatomedinas/genética , Somatomedinas/metabolismo , Inanição/metabolismo , Fatores de Tempo
9.
FASEB J ; 33(2): 2646-2658, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30307770

RESUMO

CD133 (AC133/prominin-1) has been identified as a stem cell marker and a putative cancer stem cell marker in many solid tumors. Its biologic function and molecular mechanisms remain largely elusive. Here, we show that a fly mutant for prominin-like, a homolog of mammalian CD133, shows a larger body size and excess weight accompanied with higher fat deposits as compared with the wild type. The expression levels of prominin-like are mediated by ecdysone signaling where its protein levels increase dramatically in the fat body during metamorphosis. Prominin-like mutants exhibit higher Drosophila insulin-like peptide 6 (di lp6) levels during nonfeeding stages and increased Akt/ Drosophila target of rapamycin (dTOR) signaling. On an amino acid-restricted diet, prominin-like mutants exhibit a significantly larger body size than the wild type does, similar to that which occurs upon the activation of the dTOR pathway in the fat body. Our data suggest that prominin-like functions by suppressing TOR and dilp6 signaling to control body size and weight. The identification of the physiologic function of prominin-like in Drosophila may provide valuable insight into the understanding of the metabolic function of CD133 in mammals.-Zheng, H., Zhang, Y., Chen, Y., Guo, P., Wang, X., Yuan, X., Ge, W., Yang, R., Yan, Q., Yang, X., Xi, Y. Prominin-like, a homolog of mammalian CD133, suppresses di lp6 and TOR signaling to maintain body size and weight in Drosophila.


Assuntos
Antígeno AC133/metabolismo , Tamanho Corporal , Peso Corporal , Proteínas de Drosophila/antagonistas & inibidores , Drosophila melanogaster/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Somatomedinas/antagonistas & inibidores , Antígeno AC133/genética , Animais , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Mutação , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais , Somatomedinas/genética , Somatomedinas/metabolismo
10.
Mol Biol Rep ; 46(1): 1023-1031, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30547390

RESUMO

Insulin-like growth factor (IGF) expression plays a critical role in the endocrine regulation of proliferation, differentiation, and growth in shellfish as well as in fish. The Pacific oyster, Crassostrea gigas, is a significant aquaculture species that comprises a large percentage of the Korean shellfish industry; moreover, its growth is economically important in aquaculture. However, when measuring the growth rate in shellfish, the soft tissue weight is difficult to determine because of the shell weight. In the present study, we describe an indirect method of measuring the growth rate using multiplex polymerase chain reaction (PCR) and analyzing levels of molluscan insulin-related peptide (MIP), the acid labile subunit of the IGF-binding protein complex (IGFBP ALS), and insulin-related peptide receptor (CIR) in Pacific oysters. The predicted sizes of amplicons were 776, 537, 380, and 198 bp, and the detection limit of the annealing temperatures was confirmed to be 65 °C. The annual expression of MIP and IGFBP ALS in tissues reached high levels in the winter following the condition index (CI). MIP and IGFBP ALS in male gonads and CIR in female gonads were related to the CI. This newly improved multiplex PCR provides an indirect measure of the growth rate; thus, it can be used to rapidly assess the growth rate. In addition, this method can supplement traditional growth data from oyster farms.


Assuntos
Crassostrea/crescimento & desenvolvimento , Crassostrea/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Somatomedinas/genética , Animais , Feminino , Masculino , Hibridização de Ácido Nucleico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Somatomedinas/metabolismo
11.
Genetics ; 211(1): 349-361, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30425043

RESUMO

The Caenorhabditis elegans insulin-like signaling network supports homeostasis and developmental plasticity. The genome encodes 40 insulin-like peptides and one known receptor. Feedback regulation has been reported, but the extent of feedback and its effect on signaling dynamics in response to changes in nutrient availability has not been determined. We measured messenger RNA expression for each insulin-like peptide, the receptor daf-2, components of the PI3K pathway, and its transcriptional effectors daf-16/FoxO and skn-1/Nrf at high temporal resolution during transition from a starved, quiescent state to a fed, growing state in wild type and mutants affecting daf-2/InsR and daf-16/FoxO. We also analyzed the effect of temperature on insulin-like gene expression. We found that most PI3K pathway components and insulin-like peptides are affected by signaling activity, revealing pervasive positive and negative feedback regulation at intra- and intercellular levels. Reporter gene analysis demonstrated that the daf-2/InsR agonist daf-28 positively regulates its own transcription and that the putative agonist ins-6 cross-regulates DAF-28 protein expression through feedback. Our results show that positive and negative feedback regulation of insulin-like signaling is widespread, giving rise to an organismal FoxO-to-FoxO signaling network that supports homeostasis during fluctuations in nutrient availability.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Retroalimentação Fisiológica , Receptor de Insulina/metabolismo , Transdução de Sinais , Somatomedinas/metabolismo , Animais , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Fator 1 Relacionado a NF-E2/genética , Fator 1 Relacionado a NF-E2/metabolismo , Receptor de Insulina/genética , Somatomedinas/genética
12.
Food Funct ; 9(11): 5791-5804, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30352112

RESUMO

Beta-cypermethrin (beta-CYP), which is widely used for the control of indoor and field pests, is a highly lipophilic insecticide with environmental estrogenic effects. Selenium-enriched Spirulina (Se-SP) is a novel natural antioxidant agent with a high nutritional value. This study was aimed at the investigation of the protective effects of Se-SP on the reproductive system of male zebrafish (Danio rerio) exposed to beta-CYP. We determined the protective effect of Se-SP on male zebrafish exposed to 7 nmol L-1 beta-CYP by measuring the activity of sperm and antioxidants, examining tissue sections, measuring hormone secretion levels, and analyzing the expression of related proteins and genes during spermatogenesis. We found that beta-CYP enhanced VTG synthesis and estrogen (E2) secretion, increased the number of spermatogonia and spermatocytes, and decreased the number of spermatids and Sertoli cells. However, treatment with 50 mg L-1 Se-SP (Se: 25 µmol g-1 Se-SP) almost completely ameliorated the deleterious effects of beta-CYP. The protective mechanism of Se-SP in the testes of beta-CYP-treated fish involved an enhancement of antioxidant enzyme activity and an increase in androgen secretion by the downregulation of the expression of cyp19a, nanos2, piwil1, dazl and sycp3, and the upregulation of the expression of odf3b, igf3, insl3 and dmrt1, which affected testosterone production and spermatogenesis. Our study strongly indicates that treatment with Se-SP can effectively prevent the oxidative damage to the reproductive system during spermatocyte differentiation induced by beta-CYP exposure.


Assuntos
Piretrinas/toxicidade , Selênio/farmacologia , Espermatogênese/efeitos dos fármacos , Spirulina/química , Animais , Aromatase/genética , Aromatase/metabolismo , Biomarcadores/sangue , Diferenciação Celular/efeitos dos fármacos , Regulação da Expressão Gênica , Masculino , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Reprodução , Somatomedinas/genética , Somatomedinas/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testosterona/metabolismo , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
13.
Ecotoxicol Environ Saf ; 164: 604-610, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30153642

RESUMO

Caenorhabditis elegans, a kind of model organism, was used to investigate biodegradation pathway of IPP and M1 in nematodes, in vivo toxicity from IPP and M1 and the possible underlying molecular mechanism. The results showed that both IPP and M1 could decrease lifespan, locomotion behavior, reproductive ability and AChE activity. During IPP biodegradation process, three intermediates (M1-M3) were monitored and identified. Based on the identified metabolites and their biodegradation courses, a possible biodegradation pathway was proposed. IPP was probably transformed to different three metabolites in nematodes through oxidation and elimination of methyl and propyl etc. Under the same concentration, IPP had more severe toxicity than M1 on nematodes. IPP and M1 might reduce lifespan and decrease reproductive ability through influencing insulin/IGF signaling pathway and TOR signaling pathway. They could decrease expression levels of daf-16, sgk-1, aak-2, daf-15 and rict-1 genes, which involved in IGF and TOR signaling pathway.


Assuntos
Compostos Azabicíclicos/toxicidade , Caenorhabditis elegans/efeitos dos fármacos , Indóis/toxicidade , Inseticidas/toxicidade , Piridinas/toxicidade , Acetilcolinesterase/metabolismo , Animais , Biodegradação Ambiental , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Regulação da Expressão Gênica , Longevidade/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Transdução de Sinais , Somatomedinas/genética , Somatomedinas/metabolismo
14.
Biol Reprod ; 99(6): 1235-1243, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29945206

RESUMO

Both oocyte maturation and ovulation is triggered by the luteinizing hormone (LH) surge in vertebrates, but exactly how these processes are regulated by LH remains to be fully elucidated. Previously, we found that Igf3, a fish-specific member of the igf family predominantly expressed in the gonads, could mediate the action of LH on oocyte maturation in zebrafish. Here, we further reveal the importance of Igf3 in mediating the action of LH on ovulation in zebrafish. All the four igf gene family members are expressed in the zebrafish ovary but only the igf3 transcript level is increased in hCG-induced ovulation in vivo. The expression of Igf3 protein in the follicles is also increased during ovulation. The actions of hCG on the expression of ovulatory enzymes and on ovulation itself could be largely mimicked by the recombinant zebrafish Igf3 protein. Intriguingly, the phosphorylation of Igf1r, the receptor for Igf3, could be activated by hCG in the follicular cells during ovulation. And inhibition of Igf3 signaling by Igf1r inhibitors and Igf3 antiserum could significantly attenuate the hCG-induced ovulation. Collectively, all these data support the notion that Igf3 serves as a mediator of LH action in zebrafish ovulation.


Assuntos
Hormônio Luteinizante/metabolismo , Ovulação/fisiologia , Somatomedinas/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Somatomedina/genética , Receptores de Somatomedina/metabolismo , Somatomedinas/genética , Peixe-Zebra , Proteínas de Peixe-Zebra/genética
15.
Chemosphere ; 207: 365-376, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29803886

RESUMO

Growth hormone/insulin-like growth factors (GH/IGFs) axis PCR array of zebrafish (Danio rerio) larvae was developed based on the quantification of mRNA expressions of 19 genes that were confirmed to play vital roles in the regulation of fish growth. Zebrafish embryos were exposed to each of four concentrations of the six representative chemicals, bisphenol A (BPA), perfluorooctane sulfonates (PFOS), tris (1,3-dichloroisopropyl) phosphate (TDCIPP), cadmium chloride (CdCl2), mercury (II) chloride (HgCl2) and lead (II) acetate (PbAc) from 2 h post fertilization (hpf) to 96 hpf. Developmental endpoints and transcriptional profiles of the genes involved in GH/IGFs axis of zebrafish larvae were examined at 96 hpf. Body length of zebrfish larvae was found to be a more susceptible endpoint in zebrafish embryo toxicity test than other endpoints, including survival rate, hatching rate, malformation incidence and heart rate after exposure to each of those representative chemicals selected. Perturbation of mRNA expressions of GH/IGF axis genes accompanied by decreased body length indicated that indicated that the growth inhibition observed might be attributed to the dysregulation of GH/IGFs axis. Therefore, GH/IGF axis PCR array of zebrafish larvae could be used to evaluate the effects of chemicals on GH/IGF endocrine system.


Assuntos
Embrião não Mamífero/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/genética , Larva/genética , Somatomedinas/genética , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Embrião não Mamífero/citologia , Embrião não Mamífero/efeitos dos fármacos , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/metabolismo , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Reação em Cadeia da Polimerase em Tempo Real/métodos , Testes de Toxicidade/métodos , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento
16.
Nutr. hosp ; 35(1): 185-193, ene.-feb. 2018. tab, graf
Artigo em Inglês | IBECS | ID: ibc-172107

RESUMO

Background: Teduglutide is an enterotrophic analogue of glucagon-like peptide-2, with an indirect and poorly understood mechanism of action, approved for the rehabilitation of short-bowel syndrome. This study aims to analyze the response of tissue growth factors to surgical injury and teduglutide administration on an animal model of intestinal anastomosis. Methods: Wistar rats (n = 59) were distributed into four groups: “ileal resection” or “laparotomy”, each one subdivided into “postoperative teduglutide administration” or “no treatment”; and sacrificed at the third or the seventh day, with ileal sample harvesting. Gene expression of insulin-like growth factor 1 (Igf1), vascular endothelial growth factor a (Vegfa), transforming growth factor β1 (Tgfβ1), connective tissue growth factor (Ctgf), fibroblast growth factor 2 (Fgf2), fibroblast growth factor 7 (Fgf7), epidermal growth factor (Egf), heparin-binding epidermal-like growth factor (Hbegf), platelet-derived growth factor b (Pdgfb) and glucagon-like peptide 2 receptor (Glp2r)was studied by real-time polymerase chain reaction. Results: Upregulation of Fgf7, Fgf2, Egf, Vegfaand Glp2rat the third day and of Pdgfat the seventh day was verified in the perianastomotic segment. Teduglutide administration was associated with higher fold-change of relative gene expression of Vegfa(3.6 ± 1.3 vs.1.9 ± 2.0, p = 0.0001), Hbegf(2.2 ± 2.3 vs. 1.1 ± 0.9, p = 0.001), Igf1(1.6 ± 7.6 vs. 0.9 ± 0.7, p = 0.002) and Ctgf(1.1 ± 2.1 vs. 0.6 ± 2.0, p = 0.013); and lower fold-change of Tgfβ1, Fgf7and Glp2r. Conclusions: Those results underscore the recognized role of Igf1and Hbegfas molecular mediators of the effects of teduglutide and suggest that other humoral factors, like Vegfand Ctgf, may also be relevant in the perioperative context. Induction of Vegfa, Igf1and Ctgfgene expressions might indicate a favorable influence of teduglutide on the intestinal anastomotic healing (AU)


Introducción: teduglutida es un análogo intestinotrofico do peptido-2 similar al glucagon, con un mecanismo de acción indirecto y poco conocido, aprobado para la rehabilitación del síndrome de intestino corto. Este estudio propone analizar la respuesta de los factores de crecimiento tisulares a la agresión quirúrgica y a la administración de teduglutida en un modelo animal de anastomosis intestinal. Métodos: ratones Wistar (n = 59) fueron distribuidos en cuatro grupos: "resección ileal" o "laparotomia", cada uno subdividido en "administración post-operatoria de teduglutida" o "sin tratamiento"; y sacrificados en el tercero o el séptimo dia, con recogida de muestras ileales. La expresión genica de Igf1, Vegfa, Tgfβ1, Ctgf, Fgf2, Fgf7, Egf, Hbegf, Pdgfb y Glp2r fue analizada por qRT-PCR. Resultados: en el segmento perianastomotico se verifico una sobrerregulacion de Fgf7, Fgf2, Egf, Vegfa y Glp2r al tercer dia y de Pdg al séptimo día. La administración de teduglutida se asoció con mayor cambio de la expresión génica relativa de Vegfa (3.6 ± 1.3 vs. 1.9 ± 2.0, p = 0.0001), Hbegf (2.2 ± 2.3 vs. 1.1 ± 0.9, p = 0.001), Igf1 (1.6 ± 7.6 vs. 0.9 ± 0.7, p = 0.002) y Ctgf (1.1 ± 2.1 vs. 0.6 ± 2.0, p = 0.013); y menor cambio de Tgfβ1, Fgf7 y Glp2r. Conclusiones: estos resultados refuerzan el reconocido papel de Igf1 y Hbegf como mediadores moleculares de los efectos de la teduglutida y sugieren que otros factores humorales, como Vegf y Ctgf, también pueden ser relevantes en el contexto perioperatorio. La inducción de las expresiones de los genes Vegfa, Igf1 y Ctgf podría indicar una influencia favorable de teduglutida en la cicatrización anastomotica intestinal (AU)


Assuntos
Ratos , Peptídeo 2 Semelhante ao Glucagon/genética , Síndrome do Intestino Curto/tratamento farmacológico , Somatomedinas/genética , Cicatrização/genética , Anastomose Cirúrgica , Fator A de Crescimento do Endotélio Vascular/genética , Modelos Animais de Doenças , Ratos Wistar , Expressão Gênica , Marcadores Genéticos
17.
J Dairy Sci ; 101(1): 783-793, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29055538

RESUMO

The development of the gastrointestinal tract in newborn calves is essential for sufficient nutrient uptake. An intensive milk feeding during the neonatal period may impair the rumen development in calves. The aim of this study was to investigate effects of milk replacer (MR) feeding in unlimited amounts for the first 5 wk of age on the gastrointestinal growth and development in preruminant calves at wk 9 of age. Twenty-eight newborn Holstein and Holstein × Charolais crossbred calves (19 male and 9 female) were fed MR ad libitum (ADLIB) or in restricted amounts (6 L per day; RES) until wk 5 of age. Thereafter, the MR intake of ADLIB was gradually reduced at wk 6 and 7, and all calves received 6 L of MR per day until wk 9 of age. In wk 9, calves were slaughtered and carcass and organ weight as well as rumen papilla size in the atrium, ventral sac, and ventral blind sac, and villus size of the mucosa in the small intestine (duodenum; proximal, mid, and distal jejunum; and ileum) were determined. The expression of mRNA associated with the local insulin-like growth factor (IGF) system was measured in the rumen epithelium. Ad libitum MR feeding increased MR intake and growth in ADLIB without influencing concentrate intake compared with RES. Carcass weight in wk 9 was greater in ADLIB than in RES. The density of the rumen papillae in the atrium and ventral blind sac was greater in RES than in ADLIB calves, but surface area of the epithelium was not different between groups in the investigated regions of the rumen. The mRNA abundance of IGF1 in the atrium tended to be greater and the IGFR1 mRNA abundance in the ventral sac tended to be lower in the ADLIB than in the RES feeding group. The rumen pH and volatile fatty acid concentrations were not affected by MR feeding intensity. In mid-jejunum, villus circumference was greater in ADLIB than in RES calves. In the distal jejunum, villus surface area and the villus height/crypt depth ratio were greater and the villus circumference and height tended to be greater, whereas crypt depth was smaller in ADLIB than in RES calves. The findings from this study indicate that ad libitum MR feeding for 5 wk of age followed by its gradual reduction promotes growth performance without any negative influence on gastrointestinal growth and development in dairy calves at 9 wk of age.


Assuntos
Ração Animal/análise , Bovinos/crescimento & desenvolvimento , Intestino Delgado/crescimento & desenvolvimento , Substitutos do Leite/metabolismo , Leite/metabolismo , Rúmen/metabolismo , Animais , Bovinos/genética , Bovinos/metabolismo , Dieta/veterinária , Ácidos Graxos Voláteis/metabolismo , Feminino , Trato Gastrointestinal/crescimento & desenvolvimento , Trato Gastrointestinal/metabolismo , Mucosa Intestinal/crescimento & desenvolvimento , Mucosa Intestinal/metabolismo , Intestino Delgado/metabolismo , Masculino , Rúmen/crescimento & desenvolvimento , Somatomedinas/genética , Somatomedinas/metabolismo
18.
Nat Microbiol ; 3(2): 243-252, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29180725

RESUMO

Vibrio cholerae colonizes the human terminal ileum to cause cholera, and the arthropod intestine and exoskeleton to persist in the aquatic environment. Attachment to these surfaces is regulated by the bacterial quorum-sensing signal transduction cascade, which allows bacteria to assess the density of microbial neighbours. Intestinal colonization with V. cholerae results in expenditure of host lipid stores in the model arthropod Drosophila melanogaster. Here we report that activation of quorum sensing in the Drosophila intestine retards this process by repressing V. cholerae succinate uptake. Increased host access to intestinal succinate mitigates infection-induced lipid wasting to extend survival of V. cholerae-infected flies. Therefore, quorum sensing promotes a more favourable interaction between V. cholerae and an arthropod host by reducing the nutritional burden of intestinal colonization.


Assuntos
Artrópodes/microbiologia , Intestinos/microbiologia , Percepção de Quorum/fisiologia , Vibrio cholerae/metabolismo , Vibrio cholerae/patogenicidade , Tecido Adiposo , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Modelos Animais de Doenças , Proteínas de Drosophila/genética , Drosophila melanogaster/microbiologia , Feminino , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Técnicas de Silenciamento de Genes , Interações Hospedeiro-Patógeno/fisiologia , Lipólise , Tamanho do Órgão , Transdução de Sinais , Somatomedinas/genética , Ácido Succínico/metabolismo , Triglicerídeos/metabolismo , Vibrio cholerae/genética , Vibrio cholerae/crescimento & desenvolvimento , Virulência/genética
19.
Neurology ; 90(4): e291-e297, 2018 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-29282328

RESUMO

OBJECTIVE: To examine whether genetically predicted variation in circulating insulin-like growth factor 1 (IGF1) or its binding protein, IGFBP3, are associated with risk of Alzheimer disease (AD), using a mendelian randomization study design. METHODS: We first examined disease risk by genotypes of 9 insulin-like growth factor (IGF)-related single nucleotide polymorphisms (SNPs) using published summary genome-wide association statistics from the International Genomics of Alzheimer's Project (IGAP; n = 17,008 cases; 37,154 controls). We then assessed whether any SNP-disease results replicated in an independent sample derived from the Swedish Twin Registry (n = 984 cases; 10,304 controls). RESULTS: Meta-analyses of SNP-AD results did not suggest that variation in IGF1, IGFBP3, or the molar ratio of these affect AD risk. Only one SNP appeared to affect AD risk in IGAP data. This variant is located in the gene FOXO3, implicated in human longevity. In a meta-analysis of both IGAP and secondary data, the odds ratio of AD per FOXO3 risk allele was 1.04 (95% confidence interval 1.01-1.08; p = 0.008). CONCLUSIONS: These findings suggest that circulating IGF1 and IGFBP3 are not important determinants of AD risk. FOXO3 function may influence AD development via pathways that are independent of IGF signaling (i.e., pleiotropic actions).


Assuntos
Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Somatomedinas/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Proteína Forkhead Box O3/genética , Estudo de Associação Genômica Ampla , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Masculino , Análise da Randomização Mendeliana
20.
Amino Acids ; 50(2): 293-308, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29196820

RESUMO

This study investigated the effect of agmatine (Agm) in proliferation of ovine trophecdoderm cells (oTr1) as well as the importance of the arginine decarboxylase (ADC) and agmatinase (AGMAT) alternative pathway for synthesis of polyamines in ovine conceptuses during the peri-implantation period of pregnancy. Morpholino antisense oligonucleotides (MAOs) were used to inhibit translation of mRNAs for ODC1 alone, AGMAT alone, and their combination. Rambouillet ewes (N = 50) were assigned randomly to the following treatments on Day 8 of pregnancy: MAO control (n = 10); MAO-ODC1 (n = 8); MAO-ADC (n = 6); MAO-ODC1:MAO-ADC (n = 9); or MAO-ODC1:MAO-AGMAT (n = 9). Ewes were ovario-hysterectomized on Day 16 of pregnancy to obtain uterine flushings, uterine endometrium, and conceptus tissues. Inhibition of translation of both ODC1 and AGMAT resulted in 22% of ewes having morphologically and functionally normal (elongated and healthy) conceptuses designated MAO-ODC1:MAO-AGMAT (A). But, 78% of the MAO-ODC1:MAO-AGMAT ewes had morphologically and functionally abnormal (not elongated and fragmented) conceptuses designated MAO-ODC1:MAO-AGMAT (B). The pregnancy rate was less (22%; P < 0.05) for MAO-ODC1:MAO-AGMAT ewes than for MAO-control (80%), MAO-ODC1 (75%), MAO-ADC (84%), and MAO-ODC1:MAO-ADC (44%) ewes. Moreover, inhibition of translational of both ODC1 and AGMAT mRNAs increased expression of ADC, SLC22A1, SLC22A2, and SLC22A3 mRNAs, as well as abundances of agmatine, putrescine, spermindine, and spermine in conceptus tissue. However, MAO-ODC1:AGMAT(B) ewes had greater abundances of agmatine, putrescine, and spermidine and reduced amounts of spermine in uterine flushes. Thus, in vivo knockdown of translation of ODC1 and AGMAT mRNAs increased expression of genes for the synthesis and transport of polyamines in ovine conceptuses during the peri-implantation period of pregnancy.


Assuntos
Agmatina/metabolismo , Implantação do Embrião/fisiologia , Desenvolvimento Embrionário/fisiologia , Poliaminas/metabolismo , Prenhez/fisiologia , Ovinos , Ureo-Hidrolases/metabolismo , Agmatina/análise , Agmatina/farmacologia , Sistemas de Transporte de Aminoácidos Básicos/genética , Animais , Carboxiliases/genética , Carboxiliases/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Interferon Tipo I/genética , Modelos Animais , Oligonucleotídeos Antissenso , Ornitina Descarboxilase/genética , Ornitina Descarboxilase/metabolismo , Poliaminas/análise , Gravidez , Proteínas da Gravidez/genética , Somatomedinas/genética , Ureo-Hidrolases/genética
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