The mechanisms of mitochondrial dysfunction and glucose intake decrease induced by Microcystin-LR in ovarian granulosa cells

Zhu, Jing; Liu, Kunyang; Pei, Li-Gang; Hu, Xinyue; Cai, Yuchen; Ding, Jie; Li, Dongmei; Han, Xiaodong; Wu, Jiang

doi:10.1016/j.ecoenv.2021.111931

Cited by 13 publications

(1 citation statement)

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“…Glucose uptake and metabolism in GCs supply essential energy substrates and intermediates to ensure oocyte maturation, and disturbance of the metabolic function of GCs leads to abnormalities in follicle development [ 41 , 42 , 43 ]. Glucose is metabolized through the glycolytic pathway, pentose phosphate pathway (PPP), HBP, and polyol pathway [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Feng

Sun

et al. 2022

IJMS

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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.

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