Disruption of O-GlcNAcylation Homeostasis Induced Ovarian Granulosa Cell Injury in Bovine

Autor:	Teng-Fei Wang, Zhi-Qiang Feng, Ya-Wen Sun, Shan-Jiang Zhao, Hui-Ying Zou, Hai-Sheng Hao, Wei-Hua Du, Xue-Ming Zhao, Hua-Bin Zhu, Yun-Wei Pang
Rok vydání:	2022
Předmět:	Granulosa Cells Organic Chemistry General Medicine N-Acetylglucosaminyltransferases Catalysis beta-N-Acetylhexosaminidases Computer Science Applications Acetylglucosamine Inorganic Chemistry Glucose Animals Homeostasis Cattle Female Physical and Theoretical Chemistry O-GlcNAcylation OGT OGA granulosa cells glucose TXNIP bovine Molecular Biology Protein Processing Post-Translational Spectroscopy bcl-2-Associated X Protein
Zdroj:	International Journal of Molecular Sciences; Volume 23; Issue 14; Pages: 7815
ISSN:	1422-0067
Popis:	O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a ubiquitous, reversible, and highly dynamic post-translational modification, which takes charge of almost all biological processes examined. However, little information is available regarding the molecular regulation of O-GlcNAcylation in granulosa cell function and glucose metabolism. This study focused on the impact of disrupted O-GlcNAc cycling on the proliferation and apoptosis of bovine granulosa cells, and further aimed to determine how this influenced glucose metabolism. Pharmacological inhibition of OGT with benzyl-2-acetamido-2-deoxy-α-D-galactopyranoside (BADGP) led to decreased cellular O-GlcNAc levels, as well as OGT and OGA protein expressions, whereas increasing O-GlcNAc levels with the OGA inhibitor, O-(2-acetamido-2-deoxy-D-gluco-pyranosylidene) (PUGNAc), resulted in elevated OGA protein expression and decreased OGT protein expression in granulosa cells. Dysregulated O-GlcNAc cycling reduced cell viability, downregulated the proliferation-related genes of CDC42 and PCNA transcripts, upregulated the pro-apoptotic genes of BAX and CASPASE-3 mRNA and the ratio of BAX/BCL-2, and increased the apoptotic rate. Glycolytic enzyme activities of hexokinase and pyruvate kinase, metabolite contents of pyruvate and lactate, mitochondrial membrane potential, ATP levels, and intermediate metabolic enzyme activities of succinate dehydrogenase and malate dehydrogenase involved in the tricarboxylic acid cycle, were significantly impaired in response to altered O-GlcNAc levels. Moreover, inhibition of OGT significantly increased the expression level of thioredoxin-interacting protein (TXNIP), but repression of OGA had no effect. Collectively, our results suggest that perturbation of O-GlcNAc cycling has a profound effect on granulosa cell function and glucose metabolism.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bc66261f1f6f13f1728e16059b97d277 https://pubmed.ncbi.nlm.nih.gov/35887161 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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