Document Detail

YS 49, 1-(alpha-naphtylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, regulates angiotensin II-stimulated ROS production, JNK phosphorylation and vascular smooth muscle cell proliferation via the induction of heme oxygenase-1.
MedLine Citation:
PMID:  18262205     Owner:  NLM     Status:  MEDLINE    
Overexpression of the gene for heme oxygenase (HO)-1 leads to a reduction in pressor responsiveness to angiotensin II (Ang II) in experimental animals. Using rat vascular smooth muscle cells (VSMCs), we tested whether YS 49 [1-(alpha-naphtylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline] inhibits Ang II-stimulated proliferation of VSMCs via induction of HO-1. YS 49 induced HO-1 protein production in a dose-and time-dependent manner in VSMCs. Treatment with YS 49 significantly and dose-dependently inhibited Ang II-induced VSMC proliferation, ROS production, and phosphorylation of JNK, but not P38 MAP kinase or ERK1/2. The antiproliferation effect of YS 49 was reversed by pretreatment with the HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX), or with hemoglobin, a carbon monoxide (CO) scavenger. Similarly, VSMC proliferation, ROS production and phosphorylation of JNK by Ang II were significantly inhibited in VSMCs transfected with the HO-1 gene. Thus, HO-1 and the HO-1 product CO play, at least in part, a crucial role in Ang II-stimulated VSMC proliferation through the regulation of ROS production and JNK phosphorylation. Therefore, YS 49 has potential as a therapeutic strategy for the pathogenesis of Ang II-related vascular diseases such as hypertension and atherosclerosis, via the induction of HO-1 gene activity.
Jin Ji Sun; Hye Jung Kim; Han Geuk Seo; Jae Heun Lee; Hye Sook Yun-Choi; Ki Churl Chang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-26
Journal Detail:
Title:  Life sciences     Volume:  82     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-29     Completed Date:  2008-05-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  600-7     Citation Subset:  IM    
Department of Pharmacology, School of Medicine, Gyeongsang National University 92 Chilam-dong, Jinju, South Korea.
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MeSH Terms
Angiotensin II / metabolism*
Cell Proliferation
Cells, Cultured
Enzyme Induction
Heme Oxygenase-1 / genetics,  metabolism*
JNK Mitogen-Activated Protein Kinases / metabolism*
MAP Kinase Signaling System / physiology
Mitogen-Activated Protein Kinases / metabolism
Muscle, Smooth, Vascular / cytology*
Myocytes, Smooth Muscle / cytology,  physiology*
Reactive Oxygen Species / metabolism*
Tetrahydroisoquinolines / metabolism*
Reg. No./Substance:
0/Reactive Oxygen Species; 0/Tetrahydroisoquinolines; 0/YS 49; 11128-99-7/Angiotensin II; EC Oxygenase-1; EC Mitogen-Activated Protein Kinases; EC Protein Kinases

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