title: Mitochondria-targeted antioxidant attenuates high glucose-induced P38             MAPK pathway activation in human neuroblastoma cells.
abstract: Excessive mitochondrial free radical production and the related mitogen-activated protein kinase P38 (P38 MAPK) activation are key regulators in the pathogenesis of high glucose-induced cell stress. Increasing evidence has emphasized the impact of hyperglycemia on neurons and the consequent neuronal stresses eventually resulting in neurodegeneration and neuronal death. In this study, we employed a novel mitochondria-targeted antioxidant, SS31 peptide, on high glucose-insulted neuroblastoma cells (SH-SY5Y). Our results showed that high glucose promoted significantly increased P38 phosphorylation which was efficiently suppressed by the application of the SS31 peptide under the experimental conditions. The inhibition of high glucose-induced P38 activation by the SS31 peptide was associated with the impact of the SS31 peptide on attenuating high glucose-induced mitochondrial ROS (reactive oxygen species) elevation and mitochondrial membrane potential collapse. The addition of SS31 peptide significantly attenuated high-gluose-induced apoptosis. Therefore, our study suggests that elimination of high glucose-induced mitochondrial oxidative stress helps to rescue SH-SY5Y cells from high glucose-related P38 MAPK pathway disturbances, and the SS31 peptide has the potential to serve as a new treatment strategy against hyperglycemia-instigated neuronal perturbations.
authors.affiliation: Department of Endocrinology Provincial Hospital Affiliated to Shandong University, Jinan 250021, PR China.
authors.forename: Mingfeng
authors.initials: M
authors.lastname: Cao
authors.forename: Jinjiao
authors.initials: J
authors.lastname: Jiang
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Du
authors.forename: Peng
authors.initials: P
authors.lastname: Yan
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System; D008928:Mitochondria / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D009842:Oligopeptides; D017382:Reactive Oxygen Species; C506540:arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose