Liting Tang, Ke Du, Kaiming Luo, Long Wang, Fei Hua
{"title":"缓解双酚 A 诱导的 KGN 细胞凋亡：1,25-二羟维生素 D3 通过上调 PGC-1α 表达和抑制线粒体细胞色素 c 途径发挥的治疗作用。","authors":"Liting Tang, Ke Du, Kaiming Luo, Long Wang, Fei Hua","doi":"10.1007/s42000-024-00539-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>This study investigated the potential of 1,25-dihydroxyvitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>VD<sub>3</sub>) to mitigate bisphenol A (BPA)-induced apoptosis in human ovarian granulosa KGN cells with the aim of establishing a theoretical foundation for understanding of how vitamin D improved ovarian function in patients with polycystic ovary syndrome (PCOS).</p><p><strong>Methods: </strong>The impact of varying concentrations of BPA and 1,25(OH)<sub>2</sub>VD<sub>3</sub> on KGN cell viability was elucidated. It was established that BPA-induced apoptosis in KGN cells. Subsequently, KGN cells underwent pretreatment with 1,25(OH)<sub>2</sub>VD<sub>3</sub>, followed by exposure to BPA. The apoptosis rate, reactive oxygen species (ROS) levels, and mitochondrial function of the cells were meticulously assessed, along with the expression levels of genes associated with apoptosis as well as antioxidant and mitochondrial biogenesis.</p><p><strong>Results: </strong>BPA induced a notable increase in apoptosis (P < 0.001) and oxidative stress (P < 0.001) in KGN cells, accompanied by a significant reduction in mitochondrial membrane potential (P < 0.001) and severe impairment of mitochondrial function. Following pretreatment of KGN cells with 1,25(OH)<sub>2</sub>VD<sub>3</sub>, there was a significant decrease in the apoptosis rate (P = 0.004), coupled with a reduction in ROS production (P = 0.002). Concomitantly, the upregulation of PGC-1α (P = 0.009) and SOD (P = 0.018) was observed, while mRNA expression of BAX (P = 0.011), Cyt c (P = 0.001), Apaf-1 (P = 0.012), caspase-9 (P < 0.001), and caspase-3 (P = 0.011) was downregulated. Notably, the mitigation of mitochondrial damage was evident through restored mitochondrial membrane potential (P < 0.001), as corroborated by electron microscope results.</p><p><strong>Conclusions: </strong>1,25(OH)<sub>2</sub>VD<sub>3</sub> mitigated BPA-induced damage and apoptosis in KGN cells by upregulating the expression of PGC-1α and impeding the mitochondrial cytochrome c (Cyt c) apoptotic pathway. This study established a novel theoretical foundation for utilizing vitamin D in the treatment of PCOS patients.</p>","PeriodicalId":50399,"journal":{"name":"Hormones-International Journal of Endocrinology and Metabolism","volume":" ","pages":"363-374"},"PeriodicalIF":2.4000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436470/pdf/","citationCount":"0","resultStr":"{\"title\":\"Mitigating bisphenol A-induced apoptosis in KGN cells: the therapeutic role of 1,25-dihydroxyvitamin D<sub>3</sub> through upregulation of PGC-1α expression and inhibition of the mitochondrial cytochrome c pathway.\",\"authors\":\"Liting Tang, Ke Du, Kaiming Luo, Long Wang, Fei Hua\",\"doi\":\"10.1007/s42000-024-00539-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>This study investigated the potential of 1,25-dihydroxyvitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>VD<sub>3</sub>) to mitigate bisphenol A (BPA)-induced apoptosis in human ovarian granulosa KGN cells with the aim of establishing a theoretical foundation for understanding of how vitamin D improved ovarian function in patients with polycystic ovary syndrome (PCOS).</p><p><strong>Methods: </strong>The impact of varying concentrations of BPA and 1,25(OH)<sub>2</sub>VD<sub>3</sub> on KGN cell viability was elucidated. It was established that BPA-induced apoptosis in KGN cells. Subsequently, KGN cells underwent pretreatment with 1,25(OH)<sub>2</sub>VD<sub>3</sub>, followed by exposure to BPA. The apoptosis rate, reactive oxygen species (ROS) levels, and mitochondrial function of the cells were meticulously assessed, along with the expression levels of genes associated with apoptosis as well as antioxidant and mitochondrial biogenesis.</p><p><strong>Results: </strong>BPA induced a notable increase in apoptosis (P < 0.001) and oxidative stress (P < 0.001) in KGN cells, accompanied by a significant reduction in mitochondrial membrane potential (P < 0.001) and severe impairment of mitochondrial function. Following pretreatment of KGN cells with 1,25(OH)<sub>2</sub>VD<sub>3</sub>, there was a significant decrease in the apoptosis rate (P = 0.004), coupled with a reduction in ROS production (P = 0.002). Concomitantly, the upregulation of PGC-1α (P = 0.009) and SOD (P = 0.018) was observed, while mRNA expression of BAX (P = 0.011), Cyt c (P = 0.001), Apaf-1 (P = 0.012), caspase-9 (P < 0.001), and caspase-3 (P = 0.011) was downregulated. Notably, the mitigation of mitochondrial damage was evident through restored mitochondrial membrane potential (P < 0.001), as corroborated by electron microscope results.</p><p><strong>Conclusions: </strong>1,25(OH)<sub>2</sub>VD<sub>3</sub> mitigated BPA-induced damage and apoptosis in KGN cells by upregulating the expression of PGC-1α and impeding the mitochondrial cytochrome c (Cyt c) apoptotic pathway. This study established a novel theoretical foundation for utilizing vitamin D in the treatment of PCOS patients.</p>\",\"PeriodicalId\":50399,\"journal\":{\"name\":\"Hormones-International Journal of Endocrinology and Metabolism\",\"volume\":\" \",\"pages\":\"363-374\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436470/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hormones-International Journal of Endocrinology and Metabolism\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s42000-024-00539-w\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hormones-International Journal of Endocrinology and Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s42000-024-00539-w","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/29 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Mitigating bisphenol A-induced apoptosis in KGN cells: the therapeutic role of 1,25-dihydroxyvitamin D3 through upregulation of PGC-1α expression and inhibition of the mitochondrial cytochrome c pathway.
Purpose: This study investigated the potential of 1,25-dihydroxyvitamin D3 (1,25(OH)2VD3) to mitigate bisphenol A (BPA)-induced apoptosis in human ovarian granulosa KGN cells with the aim of establishing a theoretical foundation for understanding of how vitamin D improved ovarian function in patients with polycystic ovary syndrome (PCOS).
Methods: The impact of varying concentrations of BPA and 1,25(OH)2VD3 on KGN cell viability was elucidated. It was established that BPA-induced apoptosis in KGN cells. Subsequently, KGN cells underwent pretreatment with 1,25(OH)2VD3, followed by exposure to BPA. The apoptosis rate, reactive oxygen species (ROS) levels, and mitochondrial function of the cells were meticulously assessed, along with the expression levels of genes associated with apoptosis as well as antioxidant and mitochondrial biogenesis.
Results: BPA induced a notable increase in apoptosis (P < 0.001) and oxidative stress (P < 0.001) in KGN cells, accompanied by a significant reduction in mitochondrial membrane potential (P < 0.001) and severe impairment of mitochondrial function. Following pretreatment of KGN cells with 1,25(OH)2VD3, there was a significant decrease in the apoptosis rate (P = 0.004), coupled with a reduction in ROS production (P = 0.002). Concomitantly, the upregulation of PGC-1α (P = 0.009) and SOD (P = 0.018) was observed, while mRNA expression of BAX (P = 0.011), Cyt c (P = 0.001), Apaf-1 (P = 0.012), caspase-9 (P < 0.001), and caspase-3 (P = 0.011) was downregulated. Notably, the mitigation of mitochondrial damage was evident through restored mitochondrial membrane potential (P < 0.001), as corroborated by electron microscope results.
Conclusions: 1,25(OH)2VD3 mitigated BPA-induced damage and apoptosis in KGN cells by upregulating the expression of PGC-1α and impeding the mitochondrial cytochrome c (Cyt c) apoptotic pathway. This study established a novel theoretical foundation for utilizing vitamin D in the treatment of PCOS patients.
期刊介绍：
Hormones-International Journal of Endocrinology and Metabolism is an international journal published quarterly with an international editorial board aiming at providing a forum covering all fields of endocrinology and metabolic disorders such as disruption of glucose homeostasis (diabetes mellitus), impaired homeostasis of plasma lipids (dyslipidemia), the disorder of bone metabolism (osteoporosis), disturbances of endocrine function and reproductive capacity of women and men.
Hormones-International Journal of Endocrinology and Metabolism particularly encourages clinical, translational and basic science submissions in the areas of endocrine cancers, nutrition, obesity and metabolic disorders, quality of life of endocrine diseases, epidemiology of endocrine and metabolic disorders.
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