title: MnTM-4-PyP modulates endogenous antioxidant responses and protects primary cortical neurons against oxidative stress.
abstract: OBJECTIVE
  Oxidative stress is a direct cause of injury in various neural diseases. Manganese porphyrins (MnPs), a large category of superoxide dismutase (SOD) mimics, shown universally to have effects in numerous neural disease models in vivo. Given their complex intracellular redox activities, detailed mechanisms underlying the biomedical efficacies are not fully elucidated. This study sought to investigate the regulation of endogenous antioxidant systems by a MnP (MnTM-4-PyP) and its role in the protection against neural oxidative stress.
  
  
  METHODS
  Primary cortical neurons were treated with MnTM-4-PyP prior to hydrogen peroxide-induced oxidative stress.
  
  
  RESULTS
  MnTM-4-PyP increased cell viability, reduced intracellular level of reactive oxygen species, inhibited mitochondrial apoptotic pathway, and ameliorated endoplasmic reticulum function. The protein levels and activities of endogenous SODs were elevated, but not those of catalase. SOD2 transcription was promoted in a transcription factor-specific manner. Additionally, we found FOXO3A and Sirt3 levels also increased. These effects were not observed with MnTM-4-PyP alone.
  
  
  CONCLUSIONS
  Induction of various levels of endogenous antioxidant responses by MnTM-4-PyP has indispensable functions in its protection for cortical neurons against hydrogen peroxide-induced oxidative stress.
authors.affiliation: Department of Chemical Biology, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China.
authors.forename: Kuo-Yuan
authors.initials: KY
authors.lastname: Cheng
authors.forename: Fei
authors.initials: F
authors.lastname: Guo
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Lu
authors.forename: Yuan-Zhao
authors.initials: YZ
authors.lastname: Cao
authors.forename: Tian-Chang
authors.initials: TC
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D008345:Manganese / Q000378:metabolism; D008665:Metalloporphyrins / Q000737:chemistry / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008665:Metalloporphyrins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C000604164:manganese(III) meso-tetrakis(N-methylpyridinium-4-yl)porphyrin; D008345:Manganese; D006861:Hydrogen Peroxide; D002374:Catalase
keywords: Endogenous antioxidant response; Manganese porphyrin; MnTM-4-PyP; Sirt3; Superoxide dismutase