The synergistic effect of palmitic acid and glucose on inducing endoplasmic reticulum stress-associated apoptosis in rat Schwann cells.

Abstract

Diabetic peripheral neuropathy (DPN) is a common long-term complication of diabetes mellitus accompanied with hyperglycemia and hyperlipidemia. Both high blood glucose and high blood lipids are key pathogenies for DPN. This research aims to investigate whether the combination of glucose (Glu) and palmitic acid (PA) played a synergistic role in the pathogenesis of DPN. The proliferation rate of Rat Schwann cell line RSC96 cells stimulated by different concentrations of Glu and PA were analyzed by CCK-8 assay. After the IC50 was detected for each drug, the RSC96 cells were divided into control, Glu, Glu+PA, PA, and BSA groups. The apoptosis of RSC96 cells in different groups were detected by flow cytometry. The effects of Glu and/or PA on endoplasmic reticulum (ER) stress-associated apoptotic signaling pathways were determined by Western blot and qPCR. Both Glu and PA showed similar inhibition on the proliferation of RSC96 cells in a dose-dependent manner. However, PA induced stronger apoptosis of RSC96 cells than glucose and significantly increased the levels of X-box-binding protein-1 (XBP1), C/EBP homologous protein (CHOP), and eIF2α phosphorylation, which are key proteins regulating endoplasmic reticulum (ER) stress-associated apoptotic signaling pathways. The combination of Glu and PA induced the strongest apoptosis in RSC96 cells and also activated ER stress-associated apoptotic signaling pathways. These results verified the synergistic effect of Glu and PA on inducing ER stress-associated apoptosis in RSC96 cells, and PA even induced stronger apoptosis in RSC96 cells than Glu. The present research indicated that hyperglycemia and hyperlipidemia might exert a synergistic damage during the pathogenesis of DPN, suggesting that blood lipid control is as important as blood glucose control for DPN patients.