Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 25, Issue 4-5, Pages 443-450Publisher
KARGER
DOI: 10.1159/000303049
Keywords
Polyamines; Hypertrophy; NO; Cardiomyocyte
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Funding
- National Basic Research Program of China (973 Programme) [2007CB512000]
- National Natural Science Foundation of China [30811120280, 30470688, 30700288, 30871012]
- Youth Science and Technology Special Foundation in Heilongjiang Province [QC07C109]
- Young academic backbone support program of ordinary high school in Heilongjiang Province [1153G055]
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Background: Polyamines and nitric oxide (NO) have been involved in the pathogenesis of cardiac hypertrophy. NO can regulate cardiac ion channels by direct actions on G-proteins and adenyl cyclase. The present study was undertaken to elucidate the molecular mechanism of interactions with polyamines and NO in cardiac hypertrophy. Methods: Cardiaomyocyte hypertrophy was induced by angiotensinII (AngII). Hypertrophy was estimated by cell-surface area, atrial natriuretic peptide (ANP) mRNA expression, and the immunofluorescence of phalloidin. Pretreatment with alpha-difluoromethylornithine (DFMO) was done to deplete putrescine; KT5823 pretreatment was carried out to block the nitric oxide/cGMP-dependent protein kinase type-I (NO/PKG-I) pathway. Expressions of endothelial nitric oxide synthase (eNOS), PKG-I, c-fos and c-myc were analyzed by western blotting and immunofluorescence. The intracellular concentration of free calcium ([Ca2+](i)) was determined by confocal laser scanning microscopy. Results: Hypertrophy of cardiomyocytes was induced by AngII, this caused an increase in putrescine, spermidine and total polyamine pool in association with a decreased level of NO. Expressions of eNOS and PKG-I were down-regulated, [Ca2+](i) was increased, and expressions of c-Fos and c-Myc upregulated. DFMO reversed these changes induced by AngII. Conclusions: Downregulation of polyamines inhibits cardiomyocyte hypertrophy, which is closely related to [Ca2+](i) and the NO/PKG-I pathway. Copyright (C) 2010 S. Karger AG, Basel
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