Uncoupling protein-2 attenuates palmitoleate protection against the cytotoxic production of mitochondrial reactive oxygen species in INS-1E insulinoma cells

Redox Biology

Jonathan Barlow¹  Verena Hirschberg Jensen¹  Charles Affourtit¹ 

[1] School of Biomedical and Healthcare Sciences, Plymouth University, Drake Circus, Plymouth PL4 8AA, UK;

关键词: Pancreatic beta cells;    Glucolipotoxicity;    Cytoprotection;    Mitochondrial dysfunction;    Uncoupling protein-2 (UCP2);    Reactive oxygen species;    INS-1E insulinoma cells;    Non-esterified fatty acids;    Obesity;    Type 2 diabetes;   

DOI  :  10.1016/j.redox.2014.11.009

来源: DOAJ

【 摘 要 】

High glucose and fatty acid levels impair pancreatic beta cell function. We have recently shown that palmitate-induced loss of INS-1E insulinoma cells is related to increased reactive oxygen species (ROS) production as both toxic effects are prevented by palmitoleate. Here we show that palmitate-induced ROS are mostly mitochondrial: oxidation of MitoSOX, a mitochondria-targeted superoxide probe, is increased by palmitate, whilst oxidation of the equivalent non-targeted probe is unaffected. Moreover, mitochondrial respiratory inhibition with antimycin A stimulates palmitate-induced MitoSOX oxidation. We also show that palmitate does not change the level of mitochondrial uncoupling protein-2 (UCP2) and that UCP2 knockdown does not affect palmitate-induced MitoSOX oxidation. Palmitoleate does not influence MitoSOX oxidation in INS-1E cells ±UCP2 and largely prevents the palmitate-induced effects. Importantly, UCP2 knockdown amplifies the preventive effect of palmitoleate on palmitate-induced ROS. Consistently, viability effects of palmitate and palmitoleate are similar between cells ±UCP2, but UCP2 knockdown significantly augments the palmitoleate protection against palmitate-induced cell loss at high glucose. We conclude that UCP2 neither mediates palmitate-induced mitochondrial ROS generation and the associated cell loss, nor protects against these deleterious effects. Instead, UCP2 dampens palmitoleate protection against palmitate toxicity.

【 授权许可】

Unknown