title: Heme oxygenase-1 is a novel target and antioxidant mediator of S-adenosylmethionine.
abstract: The sulfur compound and dietary supplement S-adenosylmethionine (SAM) has been reported to have cytoprotective and antioxidant properties. However, the underlying mechanisms remain unresolved. The present study investigates the effect of SAM on the expression of the antioxidant stress proteins heme oxygenase-1 (HO-1) and ferritin in endothelial cells. Induction of the HO-1/ferritin-system leads to protection of tissues against several inflammatory stimuli. SAM increased the protein and mRNA levels of HO-1 in cultured endothelial cells. Induction of HO-1 gene expression was associated with elevated ferritin protein levels and regulated at the transcriptional level via increased promoter activity. HO-1 upregulation by SAM was causally related to a decrease in NADPH-mediated production of oxygen radicals. Our results demonstrate that the HO-1/ferritin-system is a novel target of the antioxidant compound SAM.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Minnesota, McGuire Translational Research Facility, Room 4-500, 2001 6th Street SE, Minneapolis, MN 55455, USA.
authors.forename: Kati
authors.initials: K
authors.lastname: Erdmann
authors.forename: Belinda W Y
authors.initials: BW
authors.lastname: Cheung
authors.forename: Stephan
authors.initials: S
authors.lastname: Immenschuh
authors.forename: Henning
authors.initials: H
authors.lastname: Schröder
mesh_terms: D000975:Antioxidants / Q000502:physiology; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism*; D004790:Enzyme Induction; D005293:Ferritins / Q000096:biosynthesis; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D009249:NADP / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000494:pharmacology*; D014470:Umbilical Cord / Q000166:cytology; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D009249:NADP; D012436:S-Adenosylmethionine; D005293:Ferritins; D051547:Heme Oxygenase-1