RESUMO
Alcohol-associated liver disease (ALD) is caused by excessive abuse of alcohol. One of the most representative causes of ALD is the action of acetaldehyde. Acetaldehyde is a toxic material produced when alcohol is metabolized through some enzymes, and it causes endoplasmic reticulum (ER) stress, mitochondrial dysfunction, and tissue injury. In this study, we assessed the relationship between Progesterone receptor membrane component 1 (PGRMC1) and ALD because PGRMC1 is expressed in the ER and mitochondria in the liver. Using the chronic and binge alcohol feeding models, we assessed acetaldehyde level, liver damage, alcohol-degrading enzymes, and ER stress. Compared with wild-type (WT) mice ethanol-fed Pgrmc1 knockout (KO) mice had higher levels of alanine aminotransferase (ALT) and alcohol-degrading enzymes, and Pgrmc1 KO mice had high serum acetaldehyde and ER stress levels compared with WT mice with control and ethanol feeding. Loss of Pgrmc1 increased acetaldehyde production through increased expression of alcohol dehydrogenase and catalase, which led to increased ER stress and suggested that cell death was promoted. In conclusion, it has been proposed that the loss of PGRMC1 could promote ALD and cause liver damage in alcohol-abusing humans.NEW & NOTEWORTHY Loss of Pgrmc1 increased acetaldehyde production, and excess acetaldehyde consequently increased ER stress, which activates apoptosis. Since low expression of PGRMC1 is vulnerable to alcoholic liver damage, the loss of PGRMC1 expression may increase susceptibility to ALD.
Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Hepatopatias Alcoólicas , Humanos , Camundongos , Animais , Etanol/toxicidade , Etanol/metabolismo , Acetaldeído/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Fígado/metabolismo , Hepatopatias Alcoólicas/metabolismo , Estresse Oxidativo , Camundongos Knockout , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismoRESUMO
The present study aimed to investigate the regulation of placentas and uterus remodeling and involvement of estradiol in gestational diabetes mellitus. To achieve this, we established in vitro and in vivo models for gestational diabetes mellitus placentas by culturing human placental choriocarcinoma cells (BeWo) under hyperglycemic concentration and treating pregnant rats with streptozotocin. We evaluated the expression of angiogenesis-related proteins. The expression of the anti-angiogenic factor, excess placental soluble fms-like tyrosine kinase 1 was increased in our in vitro gestational diabetes mellitus model compared with the control. Moreover, the expressions of placental soluble fms-like tyrosine kinase 1 and the von Willebrand factor were also significantly elevated in the placenta of streptozotocin-treated rats. These data indicate the disruption of angiogenesis in the gestational diabetes mellitus placentas. The expression levels of connexin 43, a component of the gap junction and collagen type I alpha 2 chain, a component of the extracellular matrix, were decreased in the gestational diabetes mellitus uterus. These results suggest that uterus decidualization and placental angiogenesis are inhibited in gestational diabetes mellitus rats. Our results also showed upregulation of the expression of genes regulating estradiol synthesis as well as estrogen receptors in vivo models. Accordingly, the concentration of estradiol measured in the culture medium under hyperglycemic conditions, as well as in the serum and placenta of the streptozotocin-treated rats, was significantly elevated compared with the control groups. These results suggest that the dysregulated remodeling of the placenta and uterus may result in the elevation of estradiol and its signaling pathway in the gestational diabetes mellitus animal model to maintain pregnancy.
Assuntos
Diabetes Gestacional , Placenta , Gravidez , Feminino , Ratos , Animais , Humanos , Placenta/metabolismo , Diabetes Gestacional/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Estreptozocina/metabolismo , Útero/metabolismo , Estradiol/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The placenta regulates maternal-fetal communication, and its defect leads to significant pregnancy complications. The maternal and embryonic circulations are primitively connected in early placentation, but the function of the placenta during this developmentally essential period is relatively unknown. We thus performed a comparative proteomic analysis of the placenta before and after primary placentation and found that the metabolism and transport of lipids were characteristically activated in this period. The placental fatty acid (FA) carriers in specific placental compartments were upregulated according to gestational age, and metabolomic analysis also showed that the placental transport of FAs increased in a time-dependent manner. Further analysis of two mutant mice models with embryonic lethality revealed that lipid-related signatures could reflect the functional state of the placenta. Our findings highlight the importance of the nutrient transport function of the primary placenta in the early gestational period and the role of lipids in embryonic development. SUMMARY SENTENCE: The placenta is activated characteristically in terms of lipid transport during primary placentation, and the lipid-related signatures closely reflect the functional state of the placenta.
Assuntos
Placenta , Placentação , Animais , Ácidos Graxos/metabolismo , Feminino , Idade Gestacional , Camundongos , Placenta/metabolismo , Gravidez , ProteômicaRESUMO
Estrogen receptor-positive (ER+) breast cancer patients are recommended hormone therapy as a primary adjuvant treatment after surgery. Aromatase inhibitors (AIs) are widely administered to ER+ breast cancer patients as estrogen blockers; however, their safety remains controversial. The use of letrozole, an AI, has been reported to cause adverse cardiovascular effects. We aimed to elucidate the effects of letrozole on the cardiovascular system. Female rats exposed to letrozole for four weeks showed metabolic changes, i.e., decreased fatty acid oxidation, increased glycolysis, and hypertrophy in the left ventricle. Although lipid oxidation yields more ATP than carbohydrate metabolism, the latter predominates in the heart under pathological conditions. Reduced lipid metabolism is attributed to reduced ß-oxidation due to low circulating estrogen levels. In letrozole-treated rats, glycolysis levels were found to be increased in the heart. Furthermore, the levels of glycolytic enzymes were increased (in a high glucose medium) and the glycolytic rate was increased in vitro (H9c2 cells); the same was not true in the case of estrogen treatment. Reduced lipid metabolism and increased glycolysis can lower energy supply to the heart, resulting in predisposition to heart failure. These data suggest that a letrozole-induced cardiac metabolic remodeling, i.e., a shift from ß-oxidation to glycolysis, may induce cardiac structural remodeling.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Letrozol/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Animais , Biomarcadores , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/tratamento farmacológico , Cardiomiopatia Hipertrófica/etiologia , Cardiomiopatia Hipertrófica/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Estrogênios/metabolismo , Glicólise/efeitos dos fármacos , Hormônios/metabolismo , Imuno-Histoquímica , Oxirredução , Ratos , Remodelação Ventricular/efeitos dos fármacosRESUMO
We report a species of diplostomid fluke recovered from 3 carcasses of wild Korean raccoon dog, Nyctereutes procyonoides koreensis, in Korea. A total of 107 diplostomid flukes were recovered from the small intestines of Korean raccoon dogs, which were obtained from the Gangwon Wildlife Medical Rescue Center. Worms fixed with 10% neutral formalin were subjected to microscopic observation and those fixed in 70% ethanol were used for molecular genomic analysis. The worm was divided into 2 separate parts, forebody and hindbody, with a total length of 3,020-4,090 (3,855) µm and a width of 1,210-1,770 (1,562) µm. The boat-shaped forebody has a pair of characteristic tentacular appendage, 2 suckers, holdfast organ, and vitelline follicles. The oval to cylindrical hindbody has reproductive organs. The ovary was round or elliptical and located in the anterior of the testes. Two large testes were slightly segmented and tandemly arranged, occupying almost half of hindbody. The short uterus contained a relatively small number of unembryonated eggs sized 130-140×85-96 µm. The partial sequence of 18S rRNA of this fluke was consistent with Alaria alata. Based on the morphological and molecular characteristics, the diplostomid flukes recovered from the small intestine of Korean raccoon dogs were identified as A. alata (Digenea: Diplostomidae).
Assuntos
Cães Guaxinins , Trematódeos , Animais , Feminino , Animais Selvagens , Trematódeos/genética , República da Coreia , RNA Ribossômico 18SRESUMO
BACKGROUND: Progesterone receptor membrane component 1 (Pgrmc1) is a non-classical progesterone receptor associated with the development of the mammary gland and xenograft-induced breast cancer. Importantly, Pgrmc1 is associated with the expression of estrogen receptor alpha and can be used for predicting the prognosis of breast cancer. Whether the genetic deletion of Pgrmc1 affects the progression of breast cancer is still unclear. METHODS: We used MMTV-PyMT transgenic mice that spontaneously develop breast tumors. In backcrossed FVB Pgrmc1 knockout (KO) mice, we monitored the development of the primary tumor and lung metastasis. In MCF-7 and MDA-MB-231 tumor cell lines, the migratory activity was evaluated after Pgrmc1 knockdown. RESULTS: There was no significant difference in the development of breast cancer in terms of tumor size at 13 weeks of age between WT and Pgrmc1 KO mice. However, Pgrmc1 KO mice had a significantly longer survival duration compared with WT mice. Furthermore, Pgrmc1 KO mice exhibited a significantly lower degree of lung metastasis. Compared with those of WT mice, the tumors of Pgrmc1 KO mice had a low expression of focal adhesion kinase and epithelial-mesenchymal transition markers. PGRMC1 knockdown resulted in a significantly reduced migration rate in breast cancer cell lines. CONCLUSIONS: Pgrmc1 KO mice with breast cancer had a prolonged survival, which was accompanied by a low degree of lung metastasis. PGRMC1 showed a significant role in the migration of breast cancer cells, and may serve as a potential therapeutic target in breast cancer. Video Abstract.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Movimento Celular , Proteínas de Membrana/deficiência , Receptores de Progesterona/deficiência , Animais , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Feminino , Deleção de Genes , Humanos , Neoplasias Pulmonares/secundário , Masculino , Proteínas de Membrana/metabolismo , Camundongos Knockout , Metástase Neoplásica , Receptores de Progesterona/metabolismoRESUMO
In this study, we investigated the role of heat shock protein 70 (HSP70) in porcine epidemic diarrhoea virus (PEDV) replication. We found that PEDV infection induced strong HSP70 overexpression in the very early stage of infection. We also confirmed that HSP70 overexpression increased the speed of PEDV replication, resulting in the generation of more virions. In contrast, knockout of HSP70 in cells significantly downregulated PEDV protein expression, resulting in a significant reduction in PEDV replication. Most importantly, we confirmed that among the structural proteins of PEDV, membrane (M) proteins have this important role. We found that membrane proteins control cellular HSP70 expression in PEDV-infected cells. We confirmed HSP70/M complex formation by both immunoprecipitation and immunofluorescence assays. Additionally, PEDV M overexpression induced strong HSP70 expression. All our results clearly confirmed that in PEDV-infected cells, the M protein plays a very important role in PEDV replication in collaboration with HSP70.
Assuntos
Infecções por Coronavirus/veterinária , Proteínas M de Coronavírus/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Vírus da Diarreia Epidêmica Suína/fisiologia , Doenças dos Suínos/virologia , Replicação Viral , Animais , Infecções por Coronavirus/virologia , Biossíntese de Proteínas , Sus scrofa , SuínosRESUMO
The incidence of non-alcoholic fatty liver disease (NAFLD) increases in males aged >45 years, which indicates that androgens are associated with the development and/or progression of NAFLD, although excess dietary intake is the primary causative factor. However, it is uncertain how androgens are involved in the metabolic process of NAFLD, which is associated with the state of steatosis in hepatocytes. To investigate whether androgen receptor (AR) signaling influences NAFLD development, the state of steatosis was monitored in mouse livers and hepatocytes with or without androgens. As a result, hepatic lipid droplets, expression of AR, and phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) increased in the presence of testosterone. Concurrently, the expression of LKB1, an upstream regulator of AMPK, was increased by testosterone treatment. We observed that the fluctuation of AMPK-ACC signaling, which plays an important role in lipogenesis, depends on the presence of testosterone and AR. Additionally, we demonstrated that testosterone bound AR was recruited to the promoter of the LKB1 gene and induced LKB1 expression. Our study highlights a novel mechanism by which testosterone modulates NAFLD development by inducing the mRNA expression of LKB1.
Assuntos
Androgênios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Proteínas Serina-Treonina Quinases/metabolismo , Receptores Androgênicos/metabolismo , Proteínas Quinases Ativadas por AMP , Animais , Dieta Hiperlipídica , Perfilação da Expressão Gênica , Genômica , Hepatócitos , Lipogênese , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Proteínas Serina-Treonina Quinases/genética , Receptores Androgênicos/genéticaRESUMO
Hepatocellular carcinoma (HCC) is a male-oriented malignancy; its progression is affected by sex hormones. 17α-ethinylestradiol (EE2) is a synthetic estrogen widely used as an oral contraceptive; however, it is unknown whether EE2 regulates sex hormone action in HCC. We investigated whether EE2 influences HCC risk in male androgenic environments, using mice expressing human sex hormone-binding globulin (SHBG). Two-week-old male mice were injected with diethyl-nitrosamine (DEN, 25 mg/kg) and fed an EE2 diet for 10 weeks from 30 weeks of age. Development and characteristics of liver cancer were evaluated in 40-week-old mice via molecular and histological analyses. Although EE2 did not increase HCC progression in wild-type mice, SHBG mice exhibited remarkably higher HCC risk when fed EE2. The livers of EE2-treated SHBG mice exhibited substantially increased pro-inflammatory necrosis with high plasma levels of ALT and HMGB1, and intrahepatic injury and fibers. Additionally, increased androgen response and androgen-mediated proliferation in the livers of EE2-treated SHBG mice and EE2-exposed hepatocytes under SHBG conditions were observed. As a competitor of SHBG-androgen binding, EE2 could bind with SHBG and increase the bioavailability of androgen. Our results revealed that EE2 is a novel risk factor in androgen-dominant men, predisposing them to HCC risk.
Assuntos
Androgênios/metabolismo , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Globulina de Ligação a Hormônio Sexual/genética , Androgênios/genética , Animais , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Dietilnitrosamina/farmacologia , Modelos Animais de Doenças , Progressão da Doença , Etinilestradiol/farmacologia , Humanos , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Caracteres SexuaisRESUMO
Total 513 heterophyid flukes were collected from a carcass of wild Korean raccoon dog, Nyctereutes procyonoides koreensis, in Korea. With morphological and molecular characteristics, the flukes were identified to Cryptocotyle lata. The adult C. lata were minute, transparent, pentagonal, 522 µm long by 425 µm wide. Ceca extended into post-testicular region. Ventrogenital sac elliptical, 79 µm by 87 µm with genital pore and ventral sucker. Two testes semielliptical and slightly lobed, located in the posterior region, right testis 173 µm by 155 µm, left testis 130 µm by 134 µm. In a phylogenetic tree, the fluke specimen of this study was grouped with C. lata divergent from Cryptocotyle lingua. We report here N. procyonoides koreensis first as a natural definitive host of C. lata.
Assuntos
Heterophyidae , Trematódeos , Animais , Masculino , Filogenia , Cães Guaxinins , República da Coreia , Trematódeos/genéticaRESUMO
In this study, we intended to describe an unrecorded species of heterophyid trematode recovered from the small intestine of a Korean raccoon dog, Nyctereutes procyonoides koreensis, in Korea. A total of 13 small flukes were collected from a deceased Korean raccoon dog which was found in Chuncheon-si, Gangwon-do, Korea in May 2017. The trematode body were covered with many small spines, rectangular, broader than long, 807-1,103 µm long and 1,270-1,550 µm wide. Oral sucker in the anterior end slightly smaller than acetabulum. Pharynx muscular and well developed. Esophagus relatively long and sigmoid. Acetabulum small and located at median in anterior 2/5 portion. Ceca bifurcated at the anterior of genital pore and acetabulum and terminated at testis level. Testes larger, deeply lobed and located at the near of posterior end of body. Ovary small, triangular and located at the slight left of median and the anterior of left testis. Vitelline follicles dendritic and extend from the middle level of esophagus to the posterior portion of body. Eggs embryonated, operculated, small and 33-35×15-16 µm in size. Based on the morphological characteristics, the small heterophyid flukes recovered from the small intestines of Korean raccoon dog, N. procyonoides koreensis, were identified as Euryhelmis squamula (Digenea: Heterophyidae). Accordingly, this species of heterophyid flukes is to be a new trematode fauna in Korea by this study.
Assuntos
Heterophyidae , Trematódeos , Animais , Feminino , Masculino , Cães Guaxinins , República da CoreiaRESUMO
BACKGROUND/AIMS: Calcium homeostasis plays a crucial role in neuronal development and disease. Calbindin-D9k (CaBP-9k) acts as calcium modulators and sensors in various tissues. However, the neurobiological functions of CaBP-9k are unknown. METHODS: We used CaBP-9k knockout (KO) mice to investigate the roles of these gene in neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. We used anatomical and biochemical approaches to characterize functional abnormalities of the brain in the CaBP-9k KO mice. RESULTS: We found that the brains of CaBP-9k KO mice have increased APP/ß-amyloid, Tau, and α-synuclein accumulation and endoplasmic reticulum (ER) stress-induced apoptosis. Neurons deficient for these CaBP-9k had abnormal intracellular calcium levels and responses. ER stress inhibitor TUDCA reduced ER stress-induced apoptosis and restored ER stress- and apoptosis-related proteins expression to wild-type levels in CaBP-9k KO mice. Furthermore, treatment with TUDCA rescued the abnormal memory and motor behaviors exhibited by older CaBP-9k KO mice. CONCLUSION: Our results suggest that a loss of CaBP-9k may contribute to the onset and progression of neurodegenerative diseases.
Assuntos
Doença de Alzheimer/genética , Apoptose/genética , Calbindinas/genética , Estresse do Retículo Endoplasmático/genética , Doença de Parkinson/genética , Ácido Tauroquenodesoxicólico/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Calbindinas/metabolismo , Cálcio/metabolismo , Proliferação de Células/genética , Células Cultivadas , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/genética , Camundongos , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Atividade Motora/genética , Neurônios/metabolismo , Neurônios/patologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , RNA Interferente Pequeno , Fatores de Risco , Ácido Tauroquenodesoxicólico/farmacologia , alfa-Sinucleína/metabolismo , Proteínas tau/metabolismoRESUMO
The physiological functions of progesterone (P4) in female reproductive organs including the mammary glands are mediated via the progesterone receptor (PR), but not all P4 functions can be explained by PR-mediated signaling. Progesterone receptor membrane component 1 (PGRMC1), a potential mediator of P4 actions, plays an important role in the ovary and uterus in maintaining female fertility and pregnancy, but its function in mammary glands has not been elucidated. This study investigated the role of PGRMC1 in mouse mammary gland development. Unlike in the uterus, exogenous estrogen (E2) and/or P4 did not alter PGRMC1 expression in the mammary gland, and Pgrmc1-knockout (KO) mice displayed reduced ductal elongation and side branching in response to hormone treatment. During pregnancy, PGRMC1 was expressed within both the luminal and basal epithelium and gradually increased with gestation and decreased rapidly after parturition. Moreover, although lactogenic capacity was normal after parturition, Pgrmc1 KO resulted in defective mammary gland development from puberty until midpregnancy, while the expression of PR and its target genes was not significantly different between wild-type and Pgrmc1-KO mammary gland. These data suggest that PGRMC1 is essential for mammary gland development during puberty and pregnancy in a PR-independent manner.
Assuntos
Glândulas Mamárias Animais/crescimento & desenvolvimento , Proteínas de Membrana/metabolismo , Receptores de Progesterona/metabolismo , Animais , Estrogênios/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Lactação , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/metabolismo , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovariectomia , Gravidez , Progesterona/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Progesterona/genética , Maturidade Sexual/efeitos dos fármacos , Maturidade Sexual/genética , Maturidade Sexual/fisiologiaRESUMO
Inflammasome activation induces the maturation and secretion of interleukin (IL)-1ß and -18, and is dependent on NF-κB signaling to induce the transcription of the inflammasome components, called the priming step. This study elucidated the role of IκBζ, an atypical IκBs (inhibitor of κB) and a coactivator of NF-κB target genes, on the activation of inflammasome. Bone marrow-derived macrophages (BMDMs) that originated from IκBζ-encoding Nfkbiz gene depletion mice presented a defect in NLRP3 inflammasome activation. In addition, the Nfkbiz+/- and Nfkbiz-/- mice significantly attenuated serum IL-1ß secretion in response to a monosodium urate injection, a NLRP3 trigger, when compared with Nfkbiz-+/+ mice. The lack of IκBζ in BMDMs produced a disability in the expression of Nlrp3 and pro-Il1ß mRNAs during the priming step. In addition, ectopic IκBζ expression enhanced the Nlrp3 promoter activity, and Nlrp3 and pro-Il1ß transcription. Overall, IκBζ controlled the activation of NLRP3 inflammasome by upregulating the Nlrp3 gene during the priming step.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Inflamassomos/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Regulação para Cima/genética , Animais , Células Cultivadas , Macrófagos/metabolismo , Camundongos , Regiões Promotoras Genéticas/genética , Células RAW 264.7 , RNA Mensageiro/genética , Transdução de Sinais/genética , Transcrição Gênica/genéticaRESUMO
Adult ascarid worms from the field mice, Apodemus agrarius, were observed with a light and scanning electron microscope, and molecularly analized with 18S rRNA gene. In the scanning electron microscope, 3 prominent labia were present in the anterior end of male and female worms, but the interlabia and gubernaculum were absent. Scanning electron micrographs showed cervical alae as vestigial organs that looked like a slightly uplifted superficial sewing stitch. Total 6 pairs of post-cloacal papillae were observed on the tail of the male worms. The tail of female worms was blunt and conical shape with a spine-like structure, mucron. The eggs were sub-globular, coated with the albuminous layer and 73 by 82 µm in average size. The superficial pits of T. apodemi egg (mean 8.6×6.7 µm) are obviously bigger than those of Toxocara spp. The partial sequence of 18S rRNA showed the sequence homology of Toxocara canis (99.6%), Toxocara cati (99.4%), Toxascaris leonina (99.4%), and Toxocara vitulorum (99.2%). Conclusively, it was confirmed that ascarid nematodes, Toxocara apodemi, recovered from striped field mice in Korea are taxonomically conspecific relationship with genus Toxocara and genetic divergence from other Toxocara species.
Assuntos
Murinae/parasitologia , Toxocara/genética , Toxocara/ultraestrutura , Animais , Feminino , Humanos , Masculino , Microscopia Eletrônica de Varredura , RNA de Helmintos/genética , RNA Ribossômico 18S/genética , República da Coreia , Toxocara/classificação , Toxocara/isolamento & purificaçãoRESUMO
It is generally accepted that androgen receptors increase the risk of hepatocellular carcinoma (HCC), and that estrogen reduces risk of HCC. Many studies regarding this have involved males. We, therefore, have focused our attention on females, especially postmenopausal females, who typically have limited supplies of estrogen. By using sex hormone-binding globulin (SHBG) transgenic mice, we produced a humanoid environment, and facilitated deposition and modulation of sex hormones. After exposure to diethylnitrosamine to induce HCC and upon reaching the age of 40 weeks, mice were fed the fat-rich diet for 5 months. Fat-rich diet fed or ovariectomized (OVX) wild-type mice aged 62 weeks showed HCC progression, whereas fat-rich diet fed SHBG mice or OVX SHBG mice displayed fewer tumors. In the liver of fat-rich diet fed SHBG mice, estrogenic conditions including high levels of 17ß-estradiol and estrogen receptor alpha led to the induction of the lipogenesis inhibitor, phosphorylated acetyl-CoA carboxylase, and consequently suppressed fatty liver. The presence of plasma SHBG in HCC bearing mice suppressed the levels of steatosis and inflammation in a process mediated by estrogens and estrogen receptor alpha. Conversely, in the liver of OVX SHBG mice, lipogenic inhibition was also observed under conditions where the supply of estrogens is limited. Through in vitro experiment, it was confirmed SHBG suppresses lipogenesis via inhibition of acetyl-CoA carboxylase level. In conclusion, our results show that plasma SHBG might have a clinical impact on lipid-mediated hepatic diseases.
Assuntos
Carcinogênese/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Hepatopatia Gordurosa não Alcoólica/genética , Globulina de Ligação a Hormônio Sexual/genética , Acetil-CoA Carboxilase/genética , Animais , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Dieta Hiperlipídica , Dietilnitrosamina/toxicidade , Modelos Animais de Doenças , Estradiol/metabolismo , Receptor alfa de Estrogênio/genética , Estrogênios/metabolismo , Feminino , Humanos , Lipogênese/genética , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Menopausa/genética , Menopausa/metabolismo , Camundongos , Camundongos Transgênicos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Receptores Androgênicos/genéticaRESUMO
BACKGROUND: Women have a lower risk of hepatocellular carcinoma (HCC) than men, and the decreased possibility of HCC in women is thought to depend on estrogen levels. As a soybean-isoflavone product, genistein has estrogenic activity in various reproductive tissues, because it mimics 17ß-estradiol and binds the estrogen receptor. Though genistein is a known liver cancer suppressor, its effects have not been studies in long-term experiment, where genistein is fed to a female animal model of HCC. METHODS: Mice were treated with diethylnitrosamine (DEN) to induce HCC at 2 weeks of age and fed with supplemental genistein for 5 months, from 40 to 62 weeks of age. RESULTS: The dietary intake of genistein decreased the incidence of HCC and suppressed HCC development. Genistein induced phospho-AMPK in total liver extracts, Hep3B cells, and Raw 264.7 cells, and phospho-AMPK promoted apoptosis in liver and Hep3B cells. Moreover, phospho-AMPK down-regulated pro-inflammatory responses and ameliorated liver damage. A suppressed pro-inflammatory response with increased mitochondrial respiration was concomitantly observed after genistein treatment. CONCLUSIONS: Genistein-mediated AMPK activation increases hepatocyte apoptosis through energy-dependent caspase pathways, suppresses the inflammatory response in resident liver macrophages by increased cellular respiration, and consequently inhibits the initiation and progression of HCC.
Assuntos
Carcinoma Hepatocelular/dietoterapia , Genisteína/administração & dosagem , Neoplasias Hepáticas/dietoterapia , Proteínas Quinases/genética , Quinases Proteína-Quinases Ativadas por AMP , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Células RAW 264.7RESUMO
Intracellular calcium ion content is tightly regulated for the maintenance of cellular functions and cell survival. Calbindin-D9k (CaBP-9k) is responsible for regulating the distribution of cytosolic free-calcium ions. In this study, we aimed to investigate the effect of CaBP-9k on cell survival in pancreatic beta cells. Six-month-old wildtype CaBP-9k, CaBP-28k, and CaBP-9k/28k knockout (KO) mice were used to compare the pathological phenotypes of calcium-binding protein-deleted mice. Subsequently, the endoplasmic reticulum (ER) stress reducer tauroursodeoxycholic acid (TUDCA) was administered to wildtype and CaBP-9k KO mice. In vitro assessment of the role of CaBP-9k was performed following CaBP-9k overexpression and treatment with the ER stress inducer thapsigargin. Six-month-old CaBP-9k KO mice showed reduced islet volume and up-regulation of cell death markers resulting from ER stress, which led to pancreatic beta cell death. TUDCA treatment recovered islet volume, serum insulin level, and abdominal fat storage by CaBP-9k ablation. CaBP-9k overexpression elevated insulin secretion and recovered thapsigargin-induced ER stress in the INS-1E cell line. The results of this study show that CaBP-9k can protect pancreatic beta cell survival from ER stress and contribute to glucose homeostasis, which can reduce the risk of type 1 diabetes and provide the molecular basis for calcium supplementation to diabetic patients.
Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/prevenção & controle , Estresse do Retículo Endoplasmático , Células Secretoras de Insulina/metabolismo , Proteína G de Ligação ao Cálcio S100/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patologia , Células Secretoras de Insulina/patologia , Camundongos , Camundongos Knockout , Proteína G de Ligação ao Cálcio S100/genética , Ácido Tauroquenodesoxicólico/farmacologia , Tapsigargina/farmacologiaRESUMO
Avian trematodes, Urogonimus turdi (Digenea: Leucochloridiidae), were collected from the intestine of wild birds, Zoothera aurea, 2013-2017 in the Daejeon Metropolitan City, Korea. The body was ellipsoidal, attenuated and/or round ends, 1,987-2,120 long and 819-831 µm wide. The oral sucker was subterminal, rounded anteriorly, and 308- 425×351-432 µm in size; the prepharynx and esophagus were almost lacking; pharynx was well-developed, 142- 179×78-170 µm in size; intestine narrow, bifurcating just after pharynx, ascending to the oral sucker before looping posteriorly and terminating near the posterior end; ventral sucker larger, in almost median, 536-673×447-605 µm and approximately 1.5 times larger than oral sucker. A phylogenetic tree constructed with 18S ribosomal RNA showed inter- and intraspecific relationships. Based on these morphological and molecular findings, we report here a U. turdi from White's thrushes in Korea.
Assuntos
Doenças das Aves/parasitologia , Aves Canoras/parasitologia , Trematódeos/isolamento & purificação , Infecções por Trematódeos/veterinária , Animais , Tamanho Corporal , Feminino , Masculino , Filogenia , República da Coreia , Trematódeos/anatomia & histologia , Trematódeos/classificação , Trematódeos/genética , Infecções por Trematódeos/parasitologiaRESUMO
Present study was performed to describe the morphological and molecular characterization of Toxocara tanuki (Nematoda: Ascaridae) from Korean raccoon dog, Nyctereutes procyonoides koreensis, naturally infected in the Republic of Korea (Korea). Juvenile and adult worms of T. tanuki were recovered in 5 out of 10 raccoon dogs examined and the larval worms were detected in 15 out of 20 muscle samples (75%). Small lateral alae were observed on the cranial end of the body in male and female adults and 2 long spicules (3.0-3.5 mm) were characteristically observed in the posterior end of males. In SEM observation, 18 pairs of proximal precloacal, a precloacal median, a postcloacal median and 5 pairs of postcloacal papillae were uniquely revealed in the posterior portion of males, but the proximal papillae were not shown in the lateral ends of females. Molecular analysis on the 18S rRNA partial DNA sequences was revealed the same finding in both samples, adult worms and muscle larvae, which are closely related to T. tanuki. In conclusion, it was confirmed for the first time that T. tanuki is indigenously distributed, the Korean raccoon dog is acted as the natural definitive host of this nematode in Korea and the morphological characteristics of T. tanuki were shown in specific structure for single postcloacal median papilla in male.