Document Detail


Poly(ADP-ribose) polymerase-1-deficient mice are protected from angiotensin II-induced cardiac hypertrophy.
MedLine Citation:
PMID:  16632544     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Poly(ADP-ribose) polymerase-1 (PARP), a chromatin-bound enzyme, is activated by cell oxidative stress. Because oxidative stress is also considered a main component of angiotensin II-mediated cell signaling, it was postulated that PARP could be a downstream target of angiotensin II-induced signaling leading to cardiac hypertrophy. To determine a role of PARP in angiotensin II-induced hypertrophy, we infused angiotensin II into wild-type (PARP(+/+)) and PARP-deficient mice. Angiotensin II infusion significantly increased heart weight-to-tibia length ratio, myocyte cross-sectional area, and interstitial fibrosis in PARP(+/+) but not in PARP(-/-) mice. To confirm these results, we analyzed the effect of angiotensin II in primary cultures of cardiomyocytes. When compared with PARP(-/-) cardiomyocytes, angiotensin II (1 microM) treatment significantly increased protein synthesis in PARP(+/+) myocytes, as measured by (3)H-leucine incorporation into total cell protein. Angiotensin II-mediated hypertrophy of myocytes was accompanied with increased poly-ADP-ribosylation of nuclear proteins and depletion of cellular NAD content. When cells were treated with cell death-inducing doses of angiotensin II (10-20 microM), robust myocyte cell death was observed in PARP(+/+) but not in PARP(-/-) myocytes. This type of cell death was blocked by repletion of cellular NAD levels as well as by activation of the longevity factor Sir2alpha deacetylase, indicating that PARP induction and subsequent depletion of NAD levels are the sequence of events causing angiotensin II-mediated cardiomyocyte cell death. In conclusion, these results demonstrate that PARP is a nuclear integrator of angiotensin II-mediated cell signaling contributing to cardiac hypertrophy and suggest that this could be a novel therapeutic target for the management of heart failure.
Authors:
Jyothish B Pillai; Madhu Gupta; Senthilkumar B Rajamohan; Roberto Lang; Jai Raman; Mahesh P Gupta
Related Documents :
3074404 - M cell in the immune system of the lung.
17028264 - Cell-based tissue engineering for lung regeneration.
1540394 - Overexpression of pulmonary surfactant apoprotein a mrna in alveolar type ii cells and ...
7678904 - Chemically induced dna damage in isolated rabbit lung cells.
20933574 - Cell-directed-assembly: directing the formation of nano/bio interfaces and architecture...
130474 - The fine structure of neoplastic invasion: invasion of liver, skeletal muscle and lymph...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-04-21
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  291     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-09-15     Completed Date:  2006-11-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1545-53     Citation Subset:  IM    
Affiliation:
Dept. of Surgery, MC 5040, Univ. of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Angiotensin II / physiology*
Animals
Cardiomegaly / genetics,  physiopathology*,  prevention & control*
Cells, Cultured
Endomyocardial Fibrosis / chemically induced,  pathology,  prevention & control
Gene Expression Regulation, Enzymologic / physiology
Mice
Mice, Knockout
Muscle Cells / drug effects,  metabolism,  pathology
Myocardium / metabolism
NAD / metabolism
Oxidative Stress / physiology
Poly(ADP-ribose) Polymerases / genetics*,  physiology
Signal Transduction / genetics,  physiology
Sirtuin 1
Sirtuins / metabolism
Grant Support
ID/Acronym/Agency:
R01-HL-68083/HL/NHLBI NIH HHS; R01-HL-77788/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
11128-99-7/Angiotensin II; 53-84-9/NAD; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.4.2.30/poly(ADP-ribose)polymerase-1, mouse; EC 3.5.1.-/Sirt1 protein, mouse; EC 3.5.1.-/Sirtuin 1; EC 3.5.1.-/Sirtuins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  COX-2 contributes to the maintenance of flow-induced dilation in arterioles of eNOS-knockout mice.
Next Document:  Lifetimes of epicardial rotors in panoramic optical maps of fibrillating swine ventricles.