Journal of Steroid Biochemistry and Molecular Biology最新文献

{"title":"Drug repurposing opportunities for breast cancer and seven common subtypes.","authors":"Yilong Lin, Songsong Wang, Yun Zhang, Jing She, Yue Zhang, Ruidan Zhao, Zhongquan Qi, Ruiqin Yang, Liyi Zhang, Qingmo Yang","doi":"10.1016/j.jsbmb.2024.106652","DOIUrl":"10.1016/j.jsbmb.2024.106652","url":null,"abstract":"<p><p>Breast cancer is a substantial global health problem, and drug repurposing provides novel opportunities to address the urgent need for therapeutics. According to significant Mendelian randomization (MR) results, we identified 26 genes for overall breast cancer, 25 genes for ER+ breast cancer and 4 genes (CASP8, KCNN4, MYLK4, TNNT3) for ER- breast cancer. In order to explore the differences between 5 intrinsic subtypes, we found 29 actionable druggable genes for Luminal A breast cancer, 2 genes (IGF2 and TNNT3) for Luminal B breast cancer, 1 gene (FAAH) for Luminal B HER2 negative breast cancer, and 3 genes (CASP8, KCNN4, and TP53) for triple-negative breast cancer. After colocalization analysis, we determined OPRL1 as a prioritized target in both overall and Luminal A breast cancer. Additionally, FES and FAAH were considered prioritized targets for ER+ breast cancer. Through molecular docking, crizotinib stand out as a prioritized FES target drug repurposing opportunity with the lowest binding energy (-10.13 kJ·mol^-1) and CCK-8 assay showed ER+ cell groups were more sensitive to crizotinib than ER- cell groups. In conclusion, OPRL1 was identified as a prioritized target for both overall and Luminal A breast cancer. Moreover, FES and FAAH were recognized as prioritized targets for ER+ breast cancer.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106652"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The CaCo-2 cell junction derangement exerted by the single addition of oxysterols commonly detected in foods is markedly quenched when they are in mixture.","authors":"Noemi Iaia, Federico Canzoneri, Fiorella Biasi, Giuseppe Poli, Roberto Menta, Gabriella Testa, Paola Gamba","doi":"10.1016/j.jsbmb.2024.106648","DOIUrl":"10.1016/j.jsbmb.2024.106648","url":null,"abstract":"<p><p>The selective permeability of the gut epithelial barrier is heavily reliant on the stability of cell junctions, often challenged by a variety of dietary stressors, including non-enzymatic cholesterol oxidation products (COPs). A marked decrease of the tight junctions claudin-1 and occludin, and of the adherens junction E-cadherin was previously detected in differentiated CaCo-2 monolayers challenged by a single addition of 7β-hydroxycholesterol (7βOHC) or 7-ketocholesterol (7KC) in the lowest micromolar range. However, in the diet, oxysterols are occurring in a mixture. Hence, the aim of the present study was to evaluate whether cell incubation with all the main dietary COPs together quench the intercellular junction derangement previously observed as exerted by 7βOHC and 7KC singularly added. Two chocolate prototypes, respectively made with fresh (oxy-Mix1) or six-months stored whole milk powder (oxy-Mix2), were compared. The second prototype showed an almost double content of total COPs (3.34 µM, approximately 1337 ng /g of chocolate) than the first one (1.69 µM, approximately 675 ng /g of chocolate). Importantly, even in the CaCo-2 cell monolayers treated with six-months stored mixture of COPs oxy-Mix2, no alterations were observed of those cell junctions markedly affected by identical concentration of 7βOHC or 7KC used alone. The junctions' derangement started to be significantly evident when oxy-Mix2 was used at higher concentration (5 µM, approximately 2 µg oxysterols/g of product) or when treatments were carried out with repeated doses of oxy-Mix2 every 24 hours. Although achieved in a still widely adopted in vitro model system, these findings could orientate the definition of a safe shelf-life for dairy products, certainly for milk chocolate.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106648"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The determination of endogenous steroids in hair and fur: A systematic review of methodologies.","authors":"Padraig Maher, Martin Healy, Eamon Laird, Jelena Marunica Karšaj, Wei Gao, Lina Zgaga","doi":"10.1016/j.jsbmb.2024.106649","DOIUrl":"10.1016/j.jsbmb.2024.106649","url":null,"abstract":"<p><strong>Background: </strong>Endogenous steroid hormone assessment is essential for clinical practice. These hormones are typically measured in blood. More recently, measurement of steroids in hair samples has been gaining in popularity, so we have reviewed the methodologies used for this to-date.</p><p><strong>Methods: </strong>Ovid Medline, CINAHL, Psychinfo, and EMBASE were searched to identify manuscripts that analysed cortisol, testosterone, androstenedione, 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone sulphate (DHEAS), and/or 25-hydroxyvitamin D (25(OH)D), in hair or fur. Data related to sampling and measurement procedures were extracted and analysed.</p><p><strong>Results: </strong>The systematic review included a total of 180 papers, with 82 % published in the past 8 years; 67 % were human and 33 % animal studies. Cortisol was by far the most common analyte. Incomplete reporting on sample harvest, preparation, and measurement procedures was common. Typically, samples were collected from posterior vertex of humans or back/neck of animals, weighing between 11 and 50 mg (with a range of 1.25-1000 mg). Samples were usually stored at room temperature, often using aluminium foil. Isopropanol was the most common cleaning solution. Hair was normally powdered or segmented prior to extraction. Extraction was typically carried out over 18-24 hours using methanol. Validation and precision information was provided in 47 % of studies.</p><p><strong>Conclusions: </strong>This systematic review highlights the lack of standardisation in the analysis of endogenous steroids in hair. Reporting was typically incomplete, and assay validations were partial or absent. Together, these limit the value of these exciting new methods and hold back transition to clinical use.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106649"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characterization of archival adrenal tumor tissue from patients with ACTHindependent Cushing syndrome.","authors":"Juilee Rege, Aaron M Udager","doi":"10.1016/j.jsbmb.2024.106666","DOIUrl":"https://doi.org/10.1016/j.jsbmb.2024.106666","url":null,"abstract":"<p><p>Cushing syndrome represents a multitude of signs and symptoms associated with long-term and excessive exposure to glucocorticoids. Solitary cortisol-producing adenomas (CPAs) account for most cases of ACTH-independent Cushing syndrome (CS). Technological advances in next-generation sequencing have significantly increased our understanding about the genetic landscape of CPAs. However, the conventional approach utilizes fresh/frozen tissue samples, which are not routinely available for most clinical adrenal adenoma specimens. This coupled with the fact that CS is relatively rare reduces the accessibility to CPAs for research. In order to circumvent this issue, our group recently developed a sequencing strategy that allowed the use of formalin-fixed paraffin-embedded (FFPE) CPA samples for mutation analysis. Our streamlined approach includes the visualization and genomic DNA (gDNA) capture of the cortisol-producing regions in the tumor using immunohistochemistry (IHC)-guided techniques followed by targeted and/or whole-exome sequencing analysis. This approach has the advantage of using both prospective and retrospective CPA cohorts since FFPE pathologic specimens are routinely banked. This review discusses this advanced approach using IHC-guided gDNA capture of pathologic tissue followed by NGS as a preferred method for mutational analysis of CPAs.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106666"},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Combined Exposure to 17α-Methyltestosterone and Polystyrene Microplastics on Lipid Metabolism and the Nervous System in Danio rerio.","authors":"Tongyao Li, Gen Chen, Lu Cao, Weiya Rong, Haiyan Zhao, Zijun Xiong, Qing Liu, Jing Song, Weiwei Wang, Yu Liu, Xianzong Wang, Shaozhen Liu","doi":"10.1016/j.jsbmb.2024.106665","DOIUrl":"https://doi.org/10.1016/j.jsbmb.2024.106665","url":null,"abstract":"<p><p>Polystyrene (PS) microplastics are pervasive environmental pollutants that are harmful to aquatic organisms upon degradation. The synthetic androgen 17α-methyltestosterone (MT) is an environmental endocrine-disrupting chemical. This study aimed to systematically evaluate the combined histological and molecular effects of MT and PS exposure on the liver and brain tissues of Danio rerio with focus on lipid metabolism and neural function disruption. Female D. rerio were exposed to 50ng/L MT and 0.5mg/L PS (5 μm in diameter) for 21 d. Histological observations, real-time quantitative PCR (qPCR), and RNA-sequencing (RNA-seq) analysis were employed to assess the effects of PS and MT. These results indicated that MT and PS co-exposure caused fatty degeneration of liver cells and a significant upregulation of lipid synthesis-related genes (ACSS1, CEL, FASN, and GK5). In brain tissue, the observed effects included reduced marginal layer neuron counts, cytoplasmic loosening of central layer neurons, disordered gray matter layer cells, and vascular congestion. RNA-seq analysis further revealed significant enrichment of differentially expressed genes in the \"glycine, serine, and threonine metabolism\" and \"neuroactive ligand-receptor interaction\" signaling pathways. Thus, MT and PS co-exposure induced lipid metabolism disorders in D. rerio and influence neural signaling by altering the \"neuroactive ligand-receptor interaction\" pathway. These findings highlight the complex risks posed by environmental pollutants to aquatic life and provide critical insights for environmental protection and aquatic health research.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106665"},"PeriodicalIF":2.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer effects of alpha-lipoic acid, a potent organosulfur compound by modulating matrix metalloproteinases and apoptotic markers in osteosarcoma MG-63 cells.","authors":"Abdolreza Ahmadi, Fatemehsadat Hosseini, Mehdi Rostami, Mohammad Soukhtanloo","doi":"10.1016/j.jsbmb.2024.106664","DOIUrl":"10.1016/j.jsbmb.2024.106664","url":null,"abstract":"<p><p>Osteosarcoma (OS), an extremely aggressive form of bone tumor primarily affects young adults. Despite significant advancements in clinical trials, the ability of cancer cells to metastasize and resist apoptosis remains a major challenge. To address these issues, novel therapeutic interventions with high specificity for these processes are essential. Alpha-lipoic acid (ALA), an organosulfur compound derived from octanoic acid, possesses a range of pharmacological properties. This study hypothesizes that ALA would inhibit metastasis and induce cell apoptosis in OS. To evaluate the potential of ALA, its effects on the migration, metastasis, and cell cycle of MG-63 OS cells were assessed, along with its ability to trigger apoptosis. To these aims, MG-63 cells were exposed to varying concentrations of ALA, and cell viability was measured using the alamarBlue assay. The impact of ALA on cell cycle progression, apoptosis, migration, and metastasis was analyzed through flow cytometry, scratch assay, and gelatin zymography. After validating the expression of MMP2, MMP9, VEGF, VEGFR, BAX, BCL-2, and P53 by the GEO database, the expression levels of these genes were examined through quantitative PCR (qPCR). Eventually, molecular docking was employed to simulate the interactions between ALA and matrix metalloproteinase (MMPs). The results demonstrated that ALA significantly inhibited cell migration, induced cell cycle arrest, and promoted apoptosis by upregulating P53 and BAX expression while downregulating BCL-2 levels. Furthermore, ALA was found to suppress the activity and expression of MMP2 and MMP9 and reduce the expression of angiogenesis markers. Notably, ALA interacted directly with the active site of MMP2 and MMP9. These findings suggest that ALA has the potential to be a promising agent with anti-cancer effects on MG-63 cells, warranting further preclinical investigations.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106664"},"PeriodicalIF":2.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1,25-(OH)₂D₃ improves SD rats high-altitude pulmonary edema by inhibiting ferroptosis and ferritinophagy in alveolar epithelial cells.","authors":"Yaxuan Wang, Hong Su, Xue Lin, Chongyang Dai, Qian Cheng, Zhangchang Deng, Yangyang Yang, Xiaoyan Pu","doi":"10.1016/j.jsbmb.2024.106663","DOIUrl":"10.1016/j.jsbmb.2024.106663","url":null,"abstract":"<p><strong>Background: </strong>This study investigates the protective effects and potential mechanisms of 1,25-(OH)₂D₃ against high-altitude pulmonary edema (HAPE).</p><p><strong>Methods: </strong>Hypoxia-induced rats were administered 1,25-(OH)₂D₃ for 24, 48, and 72 hours, and we observed lung tissue injury and pulmonary edema. Immunohistochemistry (IHC) and Western blot analyses were employed to analyze the expression of markers associated with ferroptosis and ferritinophagy in rat lungs. Metabolomics analysis was conducted to investigate changes in serum lipid metabolites. We validated the mechanism of action of 1,25-(OH)₂D₃ in type II alveolar epithelial cells induced by hypoxia.</p><p><strong>Results: </strong>Our results demonstrated that hypoxic exposure significantly altered sodium-water transport in the lungs, leading to edema formation. The degree of pulmonary edema was most pronounced at 48 hours of hypoxi. Treatment with 1,25-(OH)₂D₃ improved lung function and reduced the degree of pulmonary edema in hypoxic rats. Hypoxia-induced increases in 4-HNE and MDA levels in the lungs, along with iron accumulation, were observed. Hypoxia also resulted in elevated levels of NCOA4, LC3Ⅱ, and FTH1 proteins in the lungs. Furthermore, treatment with 1,25-(OH)₂D₃ significantly inhibited ferroptosis and ferritinophagy in the lungs after hypoxia. The levels of lipid metabolites, such as L-Aspartic acid and L-Fucose, were significantly elevated in the serum of hypoxic rats. After 1,25-(OH)₂D₃ treatment, these levels exhibited a significant reduction.</p><p><strong>Conclusion: </strong>In hypoxic type II alveolar epithelial cells, 1,25-(OH)₂D₃ improved hypoxia-induced sodium-water transport, ferroptosis, and ferritinophagy, which were reversed by the autophagy agonist Rapamycin.By modulating ferroptosis and ferritinophagy, 1,25-(OH)₂D₃ mitigated the deleterious effects of hypoxia on pulmonary function.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106663"},"PeriodicalIF":2.7,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D deficiency in Mongolian men aged 15-49 years.","authors":"Tserendolgor Uush","doi":"10.1016/j.jsbmb.2024.106656","DOIUrl":"10.1016/j.jsbmb.2024.106656","url":null,"abstract":"<p><p>We aimed to estimate the prevalence of vitamin D deficiency in Mongolian men aged from 15 to 49 years at the National level as part of the Fifth National Nutrition Survey in 2016. This was a cross-sectional survey, conducted between September and November in 21 aimags of 4 economic regions of the country, and also in Ulaanbaatar. Given the regional differences in lifestyle and nutritional status, the target populations were stratified into 5 strata based on their economic region and in Ulaanbaatar, with equal samples drawn from each stratum using a cluster-randomized sampling design. A representative sample of 30 clusters [villages] was randomly selected using Probability Proportional to Size [PPS] methodology in each of the 4 regions and in Ulaanbaatar for a total of 150 cluster units. The selection of survey participants differed for the three sampling regions. Household eligibility was based on having a child 0-59 months of age, living in the household which was randomly selected from each cluster for a total of 450 households in each region. Households with a child 0-59 months of age were selected from household lists available at the kheseg or bagh level. All men 15-49 years of age who resided in the selected households were also eligible to participate in the survey. Serum concentration of 25-hydroxyvitamin D [25(OH)D] were measured using an enzyme-linked fluorescence assay in 377 men aged 15-49 years. The overall mean serum level of 25(OH)D concentration was 22.26 ± 0.48 ng/mL (95 % CI 21.31-23.21). The mean serum 25(OH)D concentrations were 19.65 ± 0.32 ng/mL (95 % CI19.01-19.82), and 33.68 ± 0.49 ng/mL (95 % CI 32.72-34.64) in vitamin D deficient, and in vitamin D sufficient subjects, respectively. The prevalence of vitamin D deficiency was 83.5 % with no significant difference in the prevalence of vitamin D deficiency by age group, economic region, area, location, education, and wealth index quintile. The prevalence of men in this study who were overweight or obese was 48.8 % and 14.6 % respectively. Although no significant difference was found between vitamin D deficiency and obesity, vitamin D deficiency was higher among men aged 30-39 and 40-49 years old by age specific analyses. The men did not take vitamin D supplements, and there is currently no vitamin D food fortification in Mongolia. The findings of this survey showed that vitamin D deficiency in men is a public health problem in Mongolia. In conclusion, vitamin D deficiency are common in Mongolian men, which indicates the need for vitamin D screening and treatment, as well as for an increased use of vitamin D supplements and for implementing vitamin D food fortification programs.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106656"},"PeriodicalIF":2.7,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1,25-dihydroxyvitamin D3 regulates enteroglial bioactivity through butyric acid pathway in a high-fat diet mouse model.","authors":"Aiwen Feng, Shaosheng Su, Qian Li, Cheng Li, Yingyan Liu, Jiasheng Qiu","doi":"10.1016/j.jsbmb.2024.106655","DOIUrl":"10.1016/j.jsbmb.2024.106655","url":null,"abstract":"<p><p>1,25-dihydroxyvitamin D3 (1,25(OH)2D3), affects enteric glial cells (EGCs) activity, but the mechanism is still unknown. The current study aimed to explore whether 1,25(OH)2D3 could regulate EGCs activity via butyrate pathway in a high-fat diet model. Male C57BL/6 J mice were fed with standard diet (SDD), or vitamin-D-deficient diet (VDD), or high-fat diet (HFD), or HFD plus sodium butyrate (SBR), or HFD plus 1,25(OH)2D3, or HFD plus S100B inhibitor ONO-2506 in vivo. CRL-2690 and Caco-2 cells were treated with palmitic acid (PA) and oleic acid (OA) complex, or S100B, or S100B plus butyric acid (BA) in vitro. 25(OH)D3, 1,25(OH)2D3, TNF-α and S100B concentrations were assayed by enzyme-linked immuno- sorbent assay (ELISA). Colonic mucosal permeability was measured by using FITC-dextran 4 kDa. Colonic butyrate was detected using high-performance liquid chromatography (HPLC). The results showed HFD decreased serum 25(OH)D3 and 1,25(OH)2D3 concentrations and colonic butyrate generation. 1,25(OH)2D3 supplementation raised butyrate production in the colon. 1,25(OH)2D3 and sodium butyrate supplementation inhibited EGCs to produce S100B and reduced colonic permeability to FITC-dextran. Inhibition of S100B pathway by ONO- 2506 decreased colonic hyperpermeability. In vitro experiments showed butyrate treatment not only reduced S100B and TNF-α secretion from PA/OA-treated CRL-2690 cells, but also decreased the permeability of S100B-treated Caco-2 cells. Collectively, 1,25(OH)2D3 elicited butyrate to suppress EGCs activation, which helped to prevent intestinal barrier injury.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106655"},"PeriodicalIF":2.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APN/AdipoRon regulates luteal steroidogenesis through AMPK/EZH2/H3K27me3 in goats.","authors":"Xiaomeng Pei, Haolin Li, Hao Yu, Wei Wang, Dagan Mao","doi":"10.1016/j.jsbmb.2024.106653","DOIUrl":"10.1016/j.jsbmb.2024.106653","url":null,"abstract":"<p><p>AMPK plays a crucial role in cellular energy metabolism and is involved in the regulation of luteal steroidogenesis by APN and its analog AdipoRon. To further explore the regulatory mechanism of AMPK in goat luteal steroidogenesis mediated by APN, cyclic and pregnant CL were utilized to assess the localization and expression of AMPK, EZH2, H3K27me3 and H3K27ac by WB and mIHC, and the interaction between AMPK and EZH2 by Co-IP. Then, isolated luteal cells were treated with APN/AdipoRon to evaluate the expression levels of AMPK, EZH2, H3K27me3 and H3K27ac. Results showed that AMPK and EZH2 were co-localized to the cytoplasm of luteal cells, and interacted as detected by Co-IP. H3K27me3 and H3K27ac were localized to the nucleus of goat luteal cells. H3K27me3 expression in late CL was significantly higher than that in early and middle CL, while the expressions of AMPK, H3K27ac and EZH2 in middle CL were significantly higher than those in early and late CL. Notably, all these proteins were expressed at similar levels between pregnancy and middle cycle, with the exception of EZH2. Following incubation with AdipoRon (25 μM) and APN (1 μg/mL) for 24 h, the expressions of AMPK and H3K27ac decreased, while H3K27me3 increased in luteal cells. Compound C (AMPK activity inhibitor) reversed the AdipoRon - induced decrease in EZH2 expression and the increase in H3K27me3 expression. The increased H3K27me3 expression and decreased steroidogenic protein (CYP11A1 and HSD3B) expression after GSK126 (EZH2 inhibitor) treatment were consistent with the effects seen after AdipoRon treatment. In conclusion, APN/AdipoRon inhibits luteal steroidogenesis by inhibiting the interaction between AMPK and EZH2, thereby promoting H3K27me3 expression.</p>","PeriodicalId":51106,"journal":{"name":"Journal of Steroid Biochemistry and Molecular Biology","volume":" ","pages":"106653"},"PeriodicalIF":2.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}