Enhancement of PPAR-beta activity by repetitive low-grade H(2)O(2) stress protects human umbilical vein endothelial cells from subsequent oxidative stress-induced apoptosis.
Repetitive stress has been shown to up-regulate antioxidant defense and increase survival after subsequent oxidative injury. The up-regulation of antioxidant defense has been identified as an underlying cause of the apoptosis-inhibitory effects exerted by repetitive stress. However, it remains unclear what the important signaling mechanisms are by which cells preexposed to low-grade stress deal with apoptosis-inducing stress. In this study, we repetitively stressed human umbilical vein endothelial cells (HUVECs) through multiple exposures to a low dose (30 microM) of H(2)O(2) in culture for 4 weeks. We then examined the effects of repetitive stress on PPAR-beta expression and activity as well as the role of PPAR-beta in the protective potency of repetitive stress. Our results show that repetitive stress enhances PPAR-beta expression and activity, thereby inhibiting oxidative stress-induced apoptosis. Further, PPAR-beta-directed antisense oligonucleotides reduced the PPAR-beta protein content, enhanced the H(2)O(2)-mediated apoptosis, and ablated the protective effect of repetitive low-grade H(2)O(2) stress. The specific PPAR-beta agonist L-165041 significantly potentiated the apoptosis induced by H(2)O(2) (p<0.05) and increased the protective effect of repetitive stress. These findings indicate that repetitive low-grade H(2)O(2) stress protects HUVECs from subsequent oxidative stress-induced apoptosis by enhancing PPAR-beta expression and activity.
Jiang
Bimei
B
Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.
Liang
Pengfei
P
Zhang
Bin
B
Huang
Xiaoyuan
X
Xiao
Xianzhong
X
D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D016376:Oligonucleotides, Antisense / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D048068:PPAR-beta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D010642:Phenoxyacetates / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology; D015533:Transcriptional Activation; D014471:Umbilical Veins / Q000473:pathology / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
C520164:4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid; D007093:Imidazoles; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D048068:PPAR-beta; D010455:Peptides; D010642:Phenoxyacetates; D011725:Pyridines; C118258:SN50 peptide; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580