Document Detail


Attenuated cardiovascular hypertrophy and oxidant generation in response to angiotensin II infusion in glutaredoxin-1 knockout mice.
MedLine Citation:
PMID:  20638471     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glutaredoxin-1 (Glrx) is a thioltransferase that regulates protein S-glutathiolation. To elucidate the role of endogenous Glrx in cardiovascular disease, Glrx knockout (KO) mice were infused with angiotensin II (Ang II) for 6days. After Ang II infusion, body weight and blood pressure were similar between WT and Glrx KO mice. However, compared to WT mice, Glrx KO mice demonstrated (1) less cardiac and aortic medial hypertrophy, (2) less oxidant generation in aorta as assessed by dihydroethidium staining and nitrotyrosine, (3) decreased phosphorylation of Akt in the heart, and (4) less expression of inducible NOS in aorta and heart. In cultured embryonic fibroblasts from Glrx KO mice, S-glutathiolation of actin was enhanced and actin depolymerization was impaired after hydrogen peroxide stimulation compared with WT cells. Furthermore, oxidant generation in phorbol ester-stimulated fibroblasts and RAW 264.7 macrophage-like cells was lower with Glrx siRNA knockdown. These data indicate that Ang II-induced oxidant production and hypertrophic responses were attenuated in Glrx KO mice, which may result from impaired NADPH oxidase activation.
Authors:
Markus M Bachschmid; Shanqin Xu; Karlene A Maitland-Toolan; Ye-Shih Ho; Richard A Cohen; Reiko Matsui
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-07-16
Journal Detail:
Title:  Free radical biology & medicine     Volume:  49     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-08-30     Completed Date:  2011-04-11     Revised Date:  2011-10-17    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1221-9     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Inc. All rights reserved.
Affiliation:
Vascular Biology Unit, Department of Medicine, Boston University, Boston, MA 02118, USA.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / administration & dosage
Animals
Aorta / pathology*
Cardiovascular Diseases / genetics,  metabolism,  pathology,  prevention & control*
Cell Line
Glutaredoxins / genetics,  metabolism*
Hypertrophy / genetics,  metabolism,  pathology,  prevention & control*
Infusion Pumps
Mice
Mice, Inbred C57BL
Mice, Knockout
Microfilaments / metabolism
Myocardium / pathology*
Nitric Oxide Synthase Type II / biosynthesis,  genetics
Oncogene Protein v-akt / genetics,  metabolism
Oxidants / metabolism
RNA, Small Interfering / genetics
Tyrosine / analogs & derivatives,  metabolism
Grant Support
ID/Acronym/Agency:
P01 HL081587/HL/NHLBI NIH HHS; P01 HL081587-030004/HL/NHLBI NIH HHS; P01 HL081587-040004/HL/NHLBI NIH HHS; P01 HL081587-050004/HL/NHLBI NIH HHS; R01 AG027080/AG/NIA NIH HHS; R01 AG027080-03/AG/NIA NIH HHS; R01 AG027080-04/AG/NIA NIH HHS; R01 AG027080-05/AG/NIA NIH HHS; R01 AG027080-05S1/AG/NIA NIH HHS; R01 HL104017/HL/NHLBI NIH HHS; R03 AG19078-01/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Glrx protein, mouse; 0/Glutaredoxins; 0/Oxidants; 0/RNA, Small Interfering; 11128-99-7/Angiotensin II; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 2.7.11.1/Oncogene Protein v-akt

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