title: YS 51, 1-(beta-naphtylmethyl)-6,7-dihydroxy-1,2,3,4,-tetrahydroisoquinoline, protects endothelial cells against hydrogen peroxide-induced injury via carbon monoxide derived from heme oxygenase-1.
abstract: Oxidative stress plays an important role in the pathophysiology of several vascular diseases such as atherosclerosis, and great attention has been placed on the protective role of heme oxygenase-1 (HO-1) for vasculature against oxidant-induced injury. We tested whether the protective effects of YS 51, 1-(beta-naphtyl-methyl)-6,7-dihydroxy-1,2,3,4,-tetrahydroisoquinoline, against hydrogen peroxide (H2O2)-induced cell injury is associated with HO-1 activity in bovine aortic endothelial cells (BAEC). YS 51 increased HO-1 expression and activity in concentration-dependent manners (10-100 microM) and time-dependent manners (1, 3, 6, 18 h), which were correlated well with its protective effect against H2O2-induced injury. Zinc protoporphyrin IX (ZnPP IX), a HO inhibitor, significantly inhibited the effect of YS 51 (50 microM). In contrast, [Ru(CO)3(Cl)2]2 (CORM-2, a CO releasing molecule) but not bilirubin protected against H2O2-induced injury. Oxyhemoglobin (HbO2) used as a CO scavenger significantly inhibited the protective effect of both YS 51 and CORM-2. Furthermore, both YS 51 and CORM-2 significantly reduced H2O2-induced intracellular reactive oxygen species (ROS) production; however, this was counteracted by ZnPP IX, HbO2 and deferoxamine. We found evidence for the involvement of PI3/Akt kinase and ERK1/2 pathways in HO-1 induction by YS-51. Taken together, we conclude that CO is, at least, responsible for the YS 51-mediated protective action of endothelial cells against oxidant stress via HO-1 gene induction, involving the activation of the PI3/Akt and ERK1/2 kinase pathways. Thus, YS 51 may be useful in oxidative stress-induced vascular disorders.
authors: Department of Pharmacology, School of Medicine and Institute of Health Sciences, Gyeongsang National University, 92 Chilam-dong, Jinju 660-751, South Korea.
authors: Ja Myung
authors: JM
authors: Heo
authors: Hye Jung
authors: HJ
authors: Kim
authors: Yu Mi
authors: YM
authors: Ha
authors: Min Kyu
authors: MK
authors: Park
authors: Young Jin
authors: YJ
authors: Kang
authors: Young Soo
authors: YS
authors: Lee
authors: Han Geuk
authors: HG
authors: Seo
authors: Jae Heun
authors: JH
authors: Lee
authors: Hye Sook
authors: HS
authors: Yun-Choi
authors: Ki Churl
authors: KC
authors: Chang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002248:Carbon Monoxide / Q000378:metabolism*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
chemical_list: C495109:1-(beta-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetra-hydroisoquinoline; D000975:Antioxidants; D017382:Reactive Oxygen Species; D044005:Tetrahydroisoquinolines; D002248:Carbon Monoxide; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1