Protective effects of peroxisome proliferator‐activated receptors γ coactivator‐1α against neuronal cell death in the hippocampal CA1 subfield after transient global ischemia

Abstract

Peroxisome proliferator-activated receptors gamma coactivator-1alpha (PGC-1alpha) may regulate the mitochondrial antioxidant defense system under many neuropathological settings. However, the exact role of PGC-1alpha in ischemic brain damage is still under debate. Based on an experimental model of transient global ischemia (TGI), this study evaluated the hypothesis that the activation of PGC-1alpha signaling pathway protects hippocampal CA1 neurons against delayed neuronal death after TGI. In Sprague-Dawley rats, significantly increased content of oxidized proteins in the hippocampal CA1 tissue was observed as early as 30 min after TGI, followed by augmentation of PGC-1alpha expression at 1 hr. Expression of uncoupling protein 2 (UCP2) and superoxide dismutases 2 (SOD2) in the hippocampal CA1 neurons was upregulated 4-48 hr after TGI. In addition, knock-down of PGC-1alpha expression by pretreatment with a specific antisense oligodeoxynucleotide in the hippocampal CA1 subfield downregulated the expression of UCP2 and SOD2 with resultant exacerbation of oxidative stress and augmentation of delayed neuronal cell death in the hippocampus after TGI. Overall, our results indicate that PGC-1alpha is induced by cerebral ischemia leading to upregulation of UCP2 and SOD2, thereby providing a neuroprotective effect against ischemic brain injury in the hippocampus by ameliorating oxidative stress.

Mitochondrial Dysfunction in Diabetic Neuropathy: a Series of Unfortunate Metabolic Events

“…This faster metabolism results in more respiratory chain electron leakage (1-2 % of transported electrons leak to generate ROS) [131] and is counter-balanced by enhanced synthesis of proteins involved in ROS scavenging. PGC-1α increases expression of thioredoxin, manganese superoxide dismutase (MnSOD), peroxiredoxin, and UCP2 in neurons, endothelial cells, and myocardium [89,132,133]. Interestingly, MnSOD expression is down in DRG in diabetes and correlates with higher ROS levels in axons [27,53].…”

Inhibition of microRNA-29c protects the brain in a rat model of prolonged hypothermic circulatory arrest

“…29 PGC1a is induced by cerebral ischemia and provides a neuroprotective effect against ischemic brain injury in the hippocampus by ameliorating oxidative stress. 30 An increased PGC-1a expression protects cultured neural cells from oxidative stress-mediated cell death. 27 Icariin protects against brain ischemic injury by increasing SIRT1 and PGC1a expression.…”

Application of recombinant peroxisome proliferator-activated receptor-γ coactivator-1α mediates neovascularization in the retina

“…In particular, PGC-1α regulates oxidative phosphorylation, mitochondrial biogenesis and respiration (22,23). Numerous previous studies have suggested that ischemia and hypoxia significantly induce the expression of PGC-1α (5)(6)(7)(8)(9)(10)(11)24,25). Arany et al (12) reported that PGC-1α was able to upregulate the expression of angiogenic factors such as VEGF, and promote the formation of new blood vessels in skeletal muscle.…”

“…Under ischemic and hypoxic conditions, the expression and transcriptional regulation activity of PGC-1α is enhanced in rat cardiac myocytes (5,6) and brain cells (7,8), rabbit renal tubular cells (9), and human skeletal muscle cells (10,11). A previous study demonstrated that PGC-1α is able to regulate an angiogenic program including vascular endothelial growth factor (VEGF) and additional angiogenic factors, in cultured muscle cells and skeletal muscle in vivo (12).…”