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1.
Cell ; 167(6): 1511-1524.e10, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27884405

RESUMO

Zika virus (ZIKV) persists in the semen of male patients, a first for flavivirus infection. Here, we demonstrate that ZIKV can induce inflammation in the testis and epididymidis, but not in the prostate or seminal vesicle, and can lead to damaged testes after 60 days post-infection in mice. ZIKV induces innate immune responses in Leydig, Sertoli, and epididymal epithelial cells, resulting in the production of pro-inflammatory cytokines/chemokines. However, ZIKV does not induce a rapid and abundant cytokine production in peritubular cell and spermatogonia, suggesting that these cells are vulnerable for ZIKV infection and could be the potential repositories for ZIKV. Our study demonstrates a correlation between ZIKV and testis infection/damage and suggests that ZIKV infection, under certain circumstances, can eventually lead to male infertility.


Assuntos
Infertilidade Masculina/virologia , Testículo/virologia , Infecção por Zika virus/virologia , Zika virus/fisiologia , Animais , Citocinas/metabolismo , Epididimo/patologia , Epididimo/virologia , Humanos , Infertilidade Masculina/patologia , Masculino , Camundongos , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Receptor de Interferon alfa e beta/genética , Testículo/patologia , Internalização do Vírus , Zika virus/isolamento & purificação , Infecção por Zika virus/patologia , Infecção por Zika virus/transmissão , Receptor Tirosina Quinase Axl
3.
Macromol Rapid Commun ; : e2400241, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38871361

RESUMO

Metal-organic frameworks (MOFs) have shown great research and application value in various types of hydrosilylation reactions. However, studies on photocatalysis-induced hydrosilylation using MOFs are extremely rare. Metal nanoparticles (MNPs)@MOFs are extensively studied for their excellent structural tunability and photocatalytic activity, but there are few reports on their application in photocatalytic hydrosilylation. Here, a novel photocatalyst consisting of platinum (Pt) nanoparticles immobilized in a MOF framework is synthesized and used for photocatalytic hydrosilylation. The effects of various factors on hydrosilylation conversion are investigated, including catalyst concentration, substrate ratio, and irradiation intensity. Furthermore, the photoreactivity of the synthesized Pt catalyst is evaluated in the presence of different concentrations of 2-chlorothixanthone as a photosensitizer. It is noteworthy that the conversion of the reaction increases with increasing catalyst concentration or photosensitizer concentration, whereas increasing the polymethylhydrosiloxane content does not lead to a significant increase in conversion. This study demonstrates the potential of MNPs@MOFs as efficient photocatalysts for photoinduced hydrosilylation reactions and paves the way for future applications in this area.

4.
Int J Mol Sci ; 24(11)2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37298147

RESUMO

Ferroptosis participates in the occurrence and development of neurological disorders. Modulating ferroptosis may have therapeutic potential in nervous system diseases. Therefore, TMTbased proteomic analysis in HT-22 cells was performed to identify erastin-induced differentially expressed proteins. The calcium-transporting ATP2B3 (ATP2B3) was screened as a target protein. ATP2B3 knockdown markedly alleviated the erastin-induced decrease in cell viability and elevated ROS (p < 0.01) and reversed the up-regulation of oxidative stress-related proteins polyubiquitin-binding protein p62 (P62), nuclear factor erythroid 2-related factor2 (NRF2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase-1 (NQO1) protein expression (p < 0.05 or p < 0.01) and the down-regulation of Kelch-like ECH-associated protein 1(KEAP1) protein expression (p < 0.01). Moreover, NRF2 knockdown, P62 inhibition, or KEAP1 overexpression rescued the erastin-induced decrease in cell viability (p < 0.05) and increase in ROS production (p < 0.01) in HT-22 cells, while simultaneous overexpression of NRF2 and P62 and knockdown of KEAP1 partially offset the relief effect of ATP2B3 inhibition. In addition, knockdown of ATP2B3, NRF2, and P62 and overexpression of KEAP1 significantly down-regulated erastin-induced high expression of the HO-1 protein, while HO-1 overexpression reversed the alleviating effects of ATP2B3 inhibition on the erastin-induced decrease in cell viability (p < 0.01) and increase in ROS production (p < 0.01) in HT-22 cells. Taken together, ATP2B3 inhibition mediates the alleviation of erastin-induced ferroptosis in HT-22 cells through the P62-KEAP1-NRF2-HO-1 pathway.


Assuntos
Ferroptose , Fator 2 Relacionado a NF-E2 , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Espécies Reativas de Oxigênio/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Proteômica , Estresse Oxidativo
5.
J Am Chem Soc ; 144(10): 4422-4430, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35143191

RESUMO

A series of novel ortho-terphenylene viologen derivatives (o-TPV2+) with through-space conjugation (TSC) via the combination of ortho-terphenylene skeletons with viologen structure is reported. Their optoelectronic properties can be adjusted by N-arylation or N-alkylation reactions. Compared with other viologen derivatives, o-TPV2+ not only exhibits strong photoluminescence but also retards the charge recombination process and stabilizes the diradical state without forming a quinoid structure due to the special TSC effect. Based on their special redox characteristics, o-TPV2+ was applied to the photocatalytic oxidative coupling of benzylamine with 96% yield. In addition, pTA-o-TPV2+ (tethered with p-toluic acid)-modified g-C3N4 was used for visible-light-driven hydrogen production for the first time, exceeding 15 times the rate over unmodified g-C3N4.

6.
Opt Express ; 30(12): 20241-20249, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-36224774

RESUMO

The large-scale and continuous production of CsPbBr3@PMMA composite film is realized by the in-situ ultrasonic spray coating method at room temperature. Through embedding CsPbBr3 nanocrystals into the hydrophobic polymer framework, the as-fabricated films (20 cm × 20 cm) exhibit uniform green emissions with a relatively high PLQYs of 76%, and could maintain 80% PL intensity after 3 months storage under ambient conditions. Assembling the green-emissive CsPbBr3@PMMA film and the red-emissive KSF@PMMA film with blue LED chip, a high-performance LCD is obtained, reaching a higher saturation with 126% and 94% color gamut of NTSC and Rec.2020, respectively. This work demonstrates that ultrasonic spray coating technique could be widely used in the large-scale fabrication of uniformly high-quality perovskite films for backlight application.

7.
Angew Chem Int Ed Engl ; 61(11): e202115298, 2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-34982500

RESUMO

Multifunctional solar energy conversion offers a feasible strategy to solve energy, environmental and water crises. Herein, a series of platinum(II)-tethered chalcogenoviologens (PtL+ -EV2+ , E=S, Se, Te) is reported, which integrate the functions of photosensitizer, electron mediator and catalyst. PtL+ -EV2+ (particularly for PtL+ -SeV2+ )-based one-component solar H2 production could be triggered not only by EDTA, but also by facultative anaerobic and aerobic bacteria relying on a simplified mechanism, along with efficient antibacterial activities. In addition, by using real pool water, PtL+ -SeV2+ achieved multiple functions, including H2 production, antibacterial action and acid removal, which supplied a new strategy to solve various problems in real life via a single system.


Assuntos
Antibacterianos/química , Calcogênios/química , Complexos de Coordenação/química , Fármacos Fotossensibilizantes/química , Platina/química , Energia Solar , Antibacterianos/síntese química , Antibacterianos/farmacologia , Calcogênios/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Escherichia coli/efeitos dos fármacos , Hidrogênio/química , Testes de Sensibilidade Microbiana , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacologia , Platina/farmacologia , Staphylococcus aureus/efeitos dos fármacos
8.
Angew Chem Int Ed Engl ; 61(42): e202209054, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-35881459

RESUMO

Two coordinated metallacycles (rhomboid for M1, hexagonal for M2) with selenoviologens (SeV2+ ) pendants were synthesized via coordination-driven hierarchical self-assembly. M1/M2 with rigid and discrete metallacyclic cores showed tunable optoelectronic properties due to strong π-π stacking and push-pull electron structures. Femtosecond transient absorption (fs-TA) revealed that the formation of macrocyclic structure can not only enhance the stability of radical cation, but also improve the efficiency of intramolecular charge transfer and produce a long-lived charge separation state. The electrochromic performances of M1/M2-based devices were exhibited to show decent radical stabilization. By using M1/M2 as the photocatalyst, the improved catalytic efficiency (>80 %) of visible-light-induced cross-dehydrogenative coupling (CDC) reactions was achieved due to the highly stable radical cations and long-lived charge separation states, which were also confirmed by fs-TA.

9.
J Biol Chem ; 295(9): 2570-2581, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31819008

RESUMO

Serum amyloid A (SAA), one of the major highly conserved acute-phase proteins in most mammals, is predominantly produced by hepatocytes and also by a variety of cells in extrahepatic tissues. It is well-known that the expression of SAA is sharply increased in bacterial infections. However, the exact physiological function of SAA during bacterial infection remains unclear. Herein, we showed that SAA expression significantly increased in abscesses of Staphylococcus aureus cutaneous infected mice, which exert direct antibacterial effects by binding to the bacterial cell surface and disrupting the cell membrane in acidic conditions. Mechanically, SAA disrupts anionic liposomes by spontaneously forming small vesicles or micelles under acidic conditions. Especially, the N-terminal region of SAA is necessary for membrane disruption and bactericidal activity. Furthermore, we found that mice deficient in SAA1/2 were more susceptible to infection by S. aureus In addition, the expression of SAA in infected skin was regulated by interleukin-6. Taken together, these findings support a key role of the SAA in host defense and may provide a novel therapeutic strategy for cutaneous bacterial infection.


Assuntos
Antibacterianos/metabolismo , Imunidade Inata , Proteína Amiloide A Sérica/metabolismo , Infecções Estafilocócicas/imunologia , Infecções Cutâneas Estafilocócicas/imunologia , Proteínas de Fase Aguda/imunologia , Proteínas de Fase Aguda/metabolismo , Animais , Antibacterianos/farmacologia , Aderência Bacteriana , Membrana Celular/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Interleucina-6/fisiologia , Camundongos , Proteína Amiloide A Sérica/imunologia , Proteína Amiloide A Sérica/farmacologia , Staphylococcus aureus/citologia , Staphylococcus aureus/ultraestrutura
10.
J Am Chem Soc ; 143(3): 1590-1597, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33393301

RESUMO

A series of novel bismuth-bridged viologen analogues, bismoviologens (BiV2+), synthesized through a combination of a bismuth atom and viologen skeleton is reported. Their optical and electrochemical properties were fine-tuned through the N-arylation or N-alkylation reactions. Bismolviologens not only showed good redox properties but also exhibited phosphorescence under ambient conditions (in air at room temperature). This phenomenon makes BiV2+ the first examples of phosphorescent viologen analogues reported to date. On the basis of the excellent and unique redox and optical properties of BiV2+, their electrophosphorochromic devices were fabricated. Furthermore, BiV2+ was used for the first time as both a photocatalyst and electron mediator in visible light-induced cross-dehydrogenative coupling reactions.

11.
J Cell Physiol ; 235(2): 1588-1600, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31309555

RESUMO

Prostate cancer (PCa) is one of the major health problems of the aging male. The roles of dysregulated microRNAs in PCa remain unclear. In this study, we mined the public published data and found that miR-487a-3p was significantly downregulated in 38 pairs of clinical prostate tumor tissues compared with the normal tissues. We further verified this result by in situ hybridization on tissue chip and quantitative real-time polymerase chain reaction (qRT-PCR) in PCa/normal cells. miR-487a-3p targeting of cyclin D1 (CCND1) was identified using bioinformatics, qRT-PCR and western blot analyses. The cellular proliferation, cell cycle, migration, and invasion were assessed by cell counting kit-8, flow cytometry analysis and transwell assay. We discovered that overexpression of miR-487a-3p suppressed PCa cell growth, migration, invasion by directly targeting CCND1. Knockdown of CCND1 in PCa cells showed similar results. Meanwhile, the expression level of CCND1 was significantly upregulated in the PCa tissues and cell lines, which presented negative correlation with the expression of miR-487a-3p. More important, we demonstrated significantly reduced growth of xenograft tumors of stable miR-487a-3p-overexpressed human PCa cells in nude mice. Taken together, for the first time, our results revealed that miR-487a-3p as a tumor suppressor of PCa could target CCND1. Our finding might reveal miR-487a-3p could be potentially contributed to the pathogenesis and a clinical biomarker or the new potential therapeutic target of PCa.


Assuntos
Ciclina D1/genética , Regulação Neoplásica da Expressão Gênica/genética , Genes Supressores de Tumor/fisiologia , MicroRNAs/genética , Neoplasias da Próstata/genética , Animais , Movimento Celular/genética , Proliferação de Células/genética , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Nus , Invasividade Neoplásica/genética , Neoplasias da Próstata/patologia
12.
Opt Express ; 27(21): 30090-30101, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684262

RESUMO

Chalcogenide glasses possess novel optical property in infrared range, which make them ideal candidates for photonic devices by laser direct writing. Precisely control of the refractive index manipulation in the material is the key to achieve high quality optical devices. In this work, diffraction gratings in chalcogenide As2Se3 thin films were fabricated with femtosecond laser direct writing and its refractive index change was carefully studied. Grating diffraction efficiency was measured from visible to near-infrared light by using multiple single-wavelength lasers and a supercontinuum laser. Clear diffraction patterns and high diffraction efficiency indicated the good optical quality of the prepared gratings. Results show that the grating with period of 5 µm inscribed under pulse energy of 30 nJ demonstrated a 1st-order diffraction efficiency of 30% at 808 nm testing wavelength, due to the changes of refractive index and absorption. The relationship of the change of refractive index and absorption coefficient of film under different laser irradiation intensity is carefully studied. The maximum refractive index change was estimated to be 0.087 at 808 nm.

13.
Angew Chem Int Ed Engl ; 58(25): 8468-8473, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-30951238

RESUMO

A series of electrochromic electron-accepting poly(chalcogenoviologen)s with multiple, stable, and reversible redox centers were used as anodic materials in organic radical lithium-ion batteries (ORLIBs). The introduction of heavy atoms (S, Se, and Te) into the viologen scaffold significantly improved the capacity and cycling stability of the ORLIBs. Notably, the poly(Te-BnV) anode was able to intercalate 20 Li ions and showed higher conductivity and insolubility in the electrolyte, thus contributing to a reversible capacity of 502 mAh g-1 at 100 mA g-1 when the Coulombic efficiency approached 100 %. The charged/discharged state of flexible electrochromic batteries fabricated from these anodic materials could be monitored visually owing to the unique electrochromic and redox properties of the materials. This study opens a promising avenue for the development of organic polymer-based electrodes for flexible hybrid visual electronics.

14.
J Am Chem Soc ; 140(32): 10099-10103, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30067344

RESUMO

A novel chiral spirocyclic amide (SPA)-derived triazolium organocatalyst has been designed and demonstrated to effect asymmetric homo- and heterodialkylations of various bisoxindoles, enabling enantioselective construction of vicinal all-carbon quaternary stereocenters. These reactions feature excellent enantio- and diastereoselectivities (up to 99% ee and >20:1 dr) as well as good to high yields (up to 89% over two steps). As an application of this methodology, the first asymmetric total synthesis of (-)-chimonanthidine has been achieved.

15.
Br J Nutr ; 117(7): 923-929, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28534724

RESUMO

To investigate the effects of maternal dietary protein restriction on offspring Fe metabolism, twenty-four second-parity Landrace×Yorkshire sows were randomly allocated to standard-protein (SP) and low-protein (LP) groups. The SP sows were fed diets containing 15 and 18 % crude protein throughout pregnancy and lactation, respectively, whereas the LP sows were subjected to 50 % dietary protein restriction. Offspring birth weight was not affected, but the body weight at weaning (P=0·06) and average daily gain (P=0·01) of the female piglets were significantly decreased. Serum Fe level in the LP piglets was markedly decreased at weaning, especially in males (P=0·03). Serum ferritin level (P=0·08) tended to be lower, yet serum transferrin was greatly higher (P=0·01) in male weaning piglets of the LP group. Duodenal expression of the divalent metal transporter 1 (DMT1) and ferroportin (FPN) was surprisingly reduced (P<0·05) at the level of protein, but not at the mRNA level, in male weaning piglets of the LP group. Male weaning piglets born to the LP sows exhibited higher hepatic hepcidin levels (P=0·09), lower hepatic expression of transferrin (P<0·01) and transferrin receptor 1 (P<0·05) at the level of mRNA. However, no significant differences were observed for hepatic Fe storage, ferritin, transferrin and transferrin receptor 1 protein expression in male weaning piglets of the two groups. These results indicate that maternal protein restriction during pregnancy and lactation influences growth of female offspring at weaning, reduces duodenal expression of Fe transporters (DMT1 and FPN) and decreases serum Fe level in male weaning piglets.


Assuntos
Anemia Ferropriva/veterinária , Proteínas de Transporte de Cátions/metabolismo , Dieta com Restrição de Proteínas/veterinária , Duodeno/metabolismo , Mucosa Intestinal/metabolismo , Fenômenos Fisiológicos da Nutrição Materna , Anemia Ferropriva/sangue , Anemia Ferropriva/etiologia , Anemia Ferropriva/metabolismo , Animais , Proteínas de Transporte de Cátions/genética , Dieta com Restrição de Proteínas/efeitos adversos , Feminino , Hepcidinas/genética , Hepcidinas/metabolismo , Ferro/sangue , Ferro/metabolismo , Lactação , Fígado/metabolismo , Masculino , Gravidez , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismo , Caracteres Sexuais , Suínos , Doenças dos Suínos/sangue , Doenças dos Suínos/etiologia , Doenças dos Suínos/metabolismo , Transferrina/análise , Transferrina/genética , Transferrina/metabolismo , Desmame , Aumento de Peso
16.
Eur J Orthod ; 38(6): 577-583, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26675477

RESUMO

OBJECTIVES: This study aimed to clarify the roles of Acid-sensing ion channel 3 (ASIC3) in orofacial pain following experimental tooth movement. MATERIALS AND METHODS: Sixty male Sprague-Dawley rats were divided into the experimental group (40g, n = 30) and the sham group (0g, n = 30). Closed coil springs were ligated between maxillary incisor and molars to achieve experimental tooth movement. Rat grimace scale (RGS) scores were assessed at 0, 1, 3, 5, 7, and 14 days after the placement of the springs. ASIC3 immunostaining was performed and the expression levels of ASIC3 were measured through integrated optical density/area in Image-Pro Plus 6.0. Moreover, 18 rats were divided into APETx2 group (n = 6), amiloride group (n = 6), and vehicle group (n = 6), and RGS scores were obtained compared among them to verify the roles of ASIC3 in orofacial pain following tooth movement. RESULTS: ASIC3 expression levels became significantly higher in the experimental group than in sham group on 1, 3, and 5 days and became similar on 7 and 14 days. Pain levels (RGS scores) increased in both groups and were significantly higher in the experimental group on 1, 3, 5, and 7 days and were similar on 14 days. Periodontal ASIC3 expression levels were correlated with orofacial pain levels following experimental tooth movement. Periodontal administrations of ASIC3 antagonists (APETx2 and amiloride) could alleviate pain. LIMITATION: This study needs to be better evidenced by RNA interference of ASIC3 in periodontal tissues in rats following experimental tooth movement. Moreover, we hope further studies would concentrate on the pain perception of ASIC3 knockout (ASIC3-/-) mice. CONCLUSIONS: Our results suggest that periodontal ASIC3 plays an important role in orofacial pain induced by experimental tooth movement.


Assuntos
Canais Iônicos Sensíveis a Ácido/fisiologia , Dor Facial/etiologia , Técnicas de Movimentação Dentária/efeitos adversos , Canais Iônicos Sensíveis a Ácido/metabolismo , Amilorida/farmacologia , Animais , Expressão Facial , Dor Facial/metabolismo , Masculino , Medição da Dor/métodos , Periodonto/metabolismo , Ratos , Ratos Sprague-Dawley
17.
Cell Tissue Res ; 362(3): 653-63, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26111495

RESUMO

Testis-specific gene 13 (TSGA13) is abundantly expressed in testis. As previous studies of TSGA13 expression pattern have all been based on mRNA analysis, it is imperative to investigate its actual protein expression. Here, we first examined TSGA13 gene tree and protein homology among species, and found that TSGA13 is relatively well conserved. Next, we detected its protein expression in normal human tissues as well as in a limited number of malignant tumors by immunohistochemistry (IHC). It was demonstrated that, in addition to testis, high expression of TSGA13 could also be observed in multiple normal tissues, including stomach, larynx, spleen, bladder, tonsil, liver and thyroid. Notably, most types of human carcinoma tissues displayed reduced expression of TSGA13 rather than their adjacent normal tissues except glioblastoma and lung cancer. Hence, the data from the current study strongly suggest the association between TSGA13 and tumor malignancy.


Assuntos
Proteínas de Neoplasias/genética , Neoplasias/genética , Especificidade de Órgãos , Proteínas/genética , Especificidade de Anticorpos/imunologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Immunoblotting , Imuno-Histoquímica , Masculino , Proteínas de Neoplasias/metabolismo , Neoplasias/patologia , Filogenia , Proteínas/metabolismo , Reprodutibilidade dos Testes , Homologia de Sequência de Aminoácidos , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia , Testículo
18.
J Insect Sci ; 152015.
Artigo em Inglês | MEDLINE | ID: mdl-25843578

RESUMO

The infestation of rice moth, Corcyras cephalonica (Lepidoptera: Galleriidae), causes severe losses in postharvest walnuts. Heat has been studied as a phytosanitary treatment to replace chemical fumigation for controlling this pest. Information on kinetics for thermal mortality of C. cephalonica is needed for developing effective postharvest phytosanitary thermal treatments of walnuts. Thermal death kinetics of fifth-instar C. cephalonica were investigated at temperatures between 44°C and 50°C at a heating rate of 5°C min(-1) using a heating block system. The results showed that thermal-death curves for C. cephalonica larvae followed a 0 order of kinetic reaction. The time to reach 100% mortality decreased with increasing temperature from 150 min at 44°C to 2.5 min at 50°C. The activation energy for controlling C. cephalonica was 466-592 kJ/mol, and the z value obtained from the thermal death time curve was 3.3°C. This kinetic model prediction could be useful in designing the thermal treatment protocol for controlling C. cephalonica in walnuts.


Assuntos
Temperatura Alta , Controle de Insetos/métodos , Mariposas/fisiologia , Animais , Morte , Larva/crescimento & desenvolvimento , Larva/fisiologia , Mariposas/crescimento & desenvolvimento
19.
Horm Behav ; 65(2): 97-105, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24333411

RESUMO

Exposure to excess glucocorticoids (GCs) during embryonic development influences offspring phenotypes and behaviors and induces epigenetic modifications of the genes in the hypothalamic-pituitary-adrenal (HPA) axis and in the serotonergic system in mammals. Whether prenatal corticosterone (CORT) exposure causes similar effects in avian species is less clear. In this study, we injected low (0.2µg) and high (1µg) doses of CORT into developing embryos on day 11 of incubation (E11) and tested the changes in aggressive behavior and hypothalamic gene expression on posthatch chickens of different ages. In ovo administration of high dose CORT significantly suppressed the growth rate from 3weeks of age and increased the frequency of aggressive behaviors, and the dosage was associated with elevated plasma CORT concentrations and significantly downregulated hypothalamic expression of arginine vasotocin (AVT) and corticotropin-releasing hormone (CRH). The hypothalamic content of glucocorticoid receptor (GR) protein was significantly decreased in the high dose group (p<0.05), whereas no changes were observed for GR mRNA. High dose CORT exposure significantly increased platelet serotonin (5-HT) uptake, decreased whole blood 5-HT concentration (p<0.05), downregulated hypothalamic tryptophan hydroxylase 1 (TPH1) mRNA and upregulated 5-HT receptor 1A (5-HTR1A) and monoamine oxidase A (MAO-A) mRNA, but not monoamine oxidase B (MAO-B). High dose CORT also significantly increased DNA methylation of the hypothalamic GR and CRH gene promoters (p<0.05). Our findings suggest that embryonic exposure to CORT programs aggressive behavior in the chicken through alterations of the HPA axis and the serotonergic system, which may involve modifications in DNA methylation.


Assuntos
Agressão/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Corticosterona/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Serotonina/metabolismo , Agressão/fisiologia , Animais , Comportamento Animal/fisiologia , Embrião de Galinha , Galinhas , Corticosterona/sangue , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Expressão Gênica/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Vasotocina/genética , Vasotocina/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-22986122

RESUMO

Glucocorticoids (GCs) are vital for embryonic development and their bioactivity is regulated by the intracellular metabolism involving 11ß-hydroxysteroid dehydrogenases (11ß-HSDs) and 20-hydroxysteroid dehydrogenase (20-HSD). Here we sought to reveal the differences in egg deposition of corticosterone and embryonic expression of corticosterone metabolic enzymes between slow and fast growing broiler chickens (Gallus gallus). Eggs of fast-growing breed contained significantly higher (P<0.05) corticosterone in the yolk and albumen, compared with that of a slow-growing breed. 11ß-HSD1 and 11ß-HSD2 were expressed in relatively higher abundance in the liver, kidney and intestine, following similar tissue-specific ontogenic patterns. In the liver, expression of both 11ß-HSD1 and 11ß-HSD2 was upregulated (P<0.05) towards hatching, yet 20-HSD displayed distinct pattern showing a significant decrease (P<0.05) on posthatch day 1 (D1). Hepatic mRNA expression of 11ß-HSD1 and 11ß-HSD2 was significantly higher in fast-growing chicken embryos at all the embryonic stages investigated and so was the hepatic protein content on embryonic day of 14 (E14) for 11ß-HSD1 and on E14 and D1 for 11ß-HSD2. 20-HSD mRNA was higher in fast-growing chicken embryos only on E14. Our data provide the first evidence that egg deposition of corticosterone, as well as the hepatic expression of glucocorticoid metabolic enzymes, differs between fast-growing and slow-growing chickens, which may account, to some extent, for the breed disparities in embryonic development.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , Galinhas/metabolismo , Corticosterona/metabolismo , Gema de Ovo/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/genética , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/genética , 20-Hidroxiesteroide Desidrogenases/genética , 20-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Western Blotting , Peso Corporal , Embrião de Galinha , Galinhas/genética , Galinhas/crescimento & desenvolvimento , Corticosterona/genética , Desenvolvimento Embrionário , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Rim/enzimologia , Fígado/citologia , Fígado/enzimologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Especificidade da Espécie , Fatores de Tempo
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