The impact of extracellular glucose concentrations on antioxidant capacity, viability, and microRNA expression in TM4 Sertoli cells

Abstract

This study investigates the impact of extracellular glucose concentrations on antioxidant capacity, viability, and microRNA (miR) expression in TM4 Sertoli cell lines. TM4 cells were cultured in high-glucose (115 µm) and low-glucose (<505 µm) conditions to simulate hyperglycemia and glucose starvation, respectively. The study measured total antioxidant capacity (TAC), malondialdehyde (MDA), total oxidant status (TOS), glutathione (GSH), glutathione disulfide (GSSG), NADP/NADPH, glutathione peroxidase (GPX), and glutathione reductase (GR) levels. MiR-17, miR-34, miR-106a, and miR-200a expression levels were assessed. Cell viability and apoptosis were evaluated using MTT assay and acridine-orange staining. Results indicated that high glucose reduced miR-17 expression while low glucose increased it. Both glucose conditions elevated miR-34, miR-106a, and miR-200a expressions. TAC levels decreased, while TOS and MDA levels increased significantly under both conditions. High glucose had no significant effect on GPX and GR levels, whereas low glucose decreased them. Both conditions led to reduced GSH levels, increased GSSG levels, and altered NADP/NADPH ratio. Increased apoptosis and decreased cell viability were observed under both glucose conditions. These findings suggest that extracellular glucose levels significantly dysregulate miRNA expression, antioxidant capacities, and redox buffer systems in TM4 cells. High glucose conditions suppress miR-17 expression, increase miR-34 and miR-106a levels, and induce reductive buffer imbalance. Conversely, low glucose conditions trigger compensatory mechanisms via increased miR-17 expression to enhance antioxidant status while reducing GPX and GR levels. These results provide insights into the molecular responses of Sertoli cells under varying glucose environments, highlighting potential therapeutic pathways for conditions like diabetes and metabolic dysfunctions.