Alpha‐lipoic acid does not alter stress protein response to acute exercise in diabetic brain

Abstract

Heat shock proteins (HSPs) are molecular chaperones which may act protective in cerebrovascular insults and peripheral diabetic neuropathy. We hypothesized that alpha-lipoic acid (LA), a natural thiol antioxidant, may enhance brain HSP response in diabetes. Rats with or without streptozotocin-induced diabetes were treated with LA or saline for 8 weeks. Half of the rats were subjected to exhaustive exercise to investigate HSP induction, and the brain tissue was analyzed. Diabetes increased constitutive HSC70 mRNA, and decreased HSP90 and glucose-regulated protein 75 (GRP75) mRNA without affecting protein levels. Exercise increased HSP90 protein and mRNA, and also GRP75 and heme oxygenase-1 (HO-1) mRNA only in non-diabetic animals. LA had no significant effect on brain HSPs, although LA increased HSC70 and HO-1 mRNA in diabetic animals and decreased HSC70 mRNA in non-diabetic animals. Eukaryotic translation elongation factor-2, essential for protein synthesis, was decreased by diabetes and suggesting a mechanism for the impaired HSP response related to translocation of the nascent chain during protein synthesis. LA supplementation does not offset the adverse effects of diabetes on brain HSP mRNA expression. Diabetes may impair HSP translation through elongation factors related to nascent chain translocation and subsequent responses to acute stress.

Elevated risk of type 2 diabetes for development of Alzheimer disease: A key role for oxidative stress in brain

“…Similarly, it was observed that the ferric nitrilotriacetate (Fe-NTA)-induced diabetes in rats was associated with an increase of HO-1 protein levels in the brain [127]. In addition, in another work, HO-1 mRNA expression in the brain of diabetic rats was unchanged with respect to the controls [128], thus leaving the information about HO-1 in the brain quite vague. Based on these data and our experience, it becomes difficult to argue a unique hypothesis about the role of HO-1 in insulin resistance in the brain because what is still missing with regard to diabetes is the data about HO activity and/or post-translational modifications.…”

Oleanolic acid protects against diabetic cardiomyopathy via modulation of the nuclear factor erythroid 2 and insulin signaling pathways

“…HO-1 is a myocardial protection factor and has anti-inflammatory, anti-oxidant, anti-apoptotic and anti-arrhythmia properties. In addition, HO-1 has an important role in cardiovascular disease and research has demonstrated that HO-1 is able to inhibit cardiac hypertrophy; however, oxidative stress leads to DCM and results in the reduction of HO-1 expression (24,25). HO-1 expression has become a universal marker of protection against oxidative stress.…”