title: Cobalt protoporphyrin induces HO-1 expression mediated partially by FOXO1 and reduces mitochondria-derived reactive oxygen species production.
abstract: BACKGROUND
  Reactive oxygen species arise in the mitochondria as byproducts of respiration and oxidase activity and have important roles in many physiological and pathophysiological conditions. The level of reactive oxygen species is regulated by a number of enzymes and physiological antioxidants, including HO-1, Sod2, catalase and COX-2, etc. And HO-1 against oxidative stress requires an increase in stress-responsive genes, such as Sod2 and catalase. Especially for the activity of HO-1, cobalt protoporphyrin is known to be a potent and effective inducer in many tissues. The transcription factor, FOXO1 is resistant to oxidative stress through downregulating reactive oxygen species production. Previous study showed that FOXO1 induces HO-1 expression by binding to HO-1 promoter. The question whether cobalt protoporphyrin induces HO-1 expression mediated by FOXO1 and subsequently lessens reactive oxygen species production remains to be elucidated.
  
  
  RESULTS
  Cobalt protoporphyrin enhances the expression of FOXO1 and facilitates FOXO1 binding to HO-1 promoter and increasing its transcriptional activity without influencing the FOXO1 protein stability. CoPP induces HO-1 and other oxidative stress-responsive genes expression, such as catalase, cytochrome c, Sod2, and COX-2, and decreases mitochondria-derived reactive oxygen species production, which are mediated partially by FOXO1.
  
  
  CONCLUSIONS
  Cobalt protoporphyrin induces HO-1 and other oxidative stress-responsive genes expression mediated partially by FOXO1, and has an important role in reducing cellular reactive oxygen species level. Cobalt protoporphyrin may be a more promising therapeutic agent to upregulate some antioxidantive genes.
authors.affiliation: The National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Meixia
authors.initials: M
authors.lastname: Li
authors.forename: Haifeng
authors.initials: H
authors.lastname: Xu
authors.forename: Jin
authors.initials: J
authors.lastname: Zuo
authors.forename: Fude
authors.initials: F
authors.lastname: Fang
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Chang
mesh_terms: D000818:Animals; D002460:Cell Line; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D018384:Oxidative Stress / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D055550:Protein Stability; D011524:Protoporphyrins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1