Downregulation of the Ornithine Decarboxylase/polyamine System Inhibits Angiotensin-inducedHypertrophy of Cardiomyocytes Through the NO/cGMP-dependent Protein Kinase Type-I Pathway
Cell Physiol Biochem 2010; 25: 441-448，-0001，（）：
Background: Polyamines and nitric oxide (NO) havebeen involved in the pathogenesis of cardiachypertrophy. NO can regulate cardiac ion channelsby direct actions on G-proteins and adenyl cyclase.The present study was undertaken to elucidate themolecular mechanism of interactions with polyaminesand NO in cardiac hypertrophy. Methods: Cardiaomyocytehypertrophy was induced by angiotensinII(AngII). Hypertrophy was estimated by cell-surfacearea, atrial natriuretic peptide (ANP) mRNAexpression, and the immunofluorescence of phalloidin.Pretreatment with alpha-difluoromethylornithine(DFMO) was done to deplete putrescine; KT5823pretreatment was carried out to block the nitric oxide/cGMP-dependent protein kinase type-I (NO/PKG-I)pathway. Expressions of endothelial nitric oxidesynthase (eNOS), PKG-I, c-fos and c-myc wereanalyzed by western blotting and immunofluorescence.The intracellular concentration of freecalcium ([Ca2+]i) was determined by confocal laserscanning microscopy. Results: Hypertrophy ofcardiomyocytes was induced by AngII, this caused anincrease in putrescine, spermidine and total polyaminepool 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 andc-Myc upregulated. DFMO reversed these changesinduced by AngII. Conclusions: Downregulation ofpolyamines inhibits cardiomyocyte hypertrophy, whichis closely related to [Ca2+]i and the NO/PKG-I pathway.