title: Attenuated SAG expression exacerbates 4-hydroxy-2-nonenal-induced apoptosis and hypertrophy of H9c2 cardiomyocytes.
abstract: Oxidative stress, associated with the accumulation of reactive oxygen species (ROS), results in numerous and detrimental effects on the myocardium such as the induction of apoptotic cell death, hypertrophy, fibrosis, dysfunction, and dilatation. The product of sensitive to apoptosis gene (SAG) is a RING finger protein that has been shown to have a protective effect against apoptosis induced by oxidative stress in various cell types. The major reactive aldehydic product of lipid peroxidation, 4-hydroxy-2-nonenal (HNE), is believed to be largely responsible for cytopathological effects observed during oxidative stress. In the present study, we showed that the transfection of H9c2 clonal myoblastic cells with small interfering RNA (siRNA) specific for SAG markedly attenuated SAG expression and exacerbates HNE-induced apoptosis and hypertrophy. The knockdown of SAG expression resulted in the modulation of cellular redox status, mitochondrial function, and cellular oxidative damage. Taken together, our results showed that the suppression of SAG expression by siRNA enhanced HNE-induced apoptosis and hypertrophy of cultured cardiomyocytes via the disruption of the cellular redox balance. Given the importance of the SAG protein in the regulation of the redox status of cardiomyocytes, we conclude that this protein may be a potential new target in the development of therapeutic agents for the prevention of cardiovascular diseases.
authors: School of Life Sciences and Biotechnology, BK21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University , Taegu , Republic of Korea.
authors: J H
authors: JH
authors: Park
authors: J H
authors: JH
authors: Lee
authors: J-W
authors: JW
authors: Park
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006984:Hypertrophy; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats
chemical_list: D000447:Aldehydes; D002352:Carrier Proteins; C573100:SAG protein, mouse; C027576:4-hydroxy-2-nonenal
keywords: 4-hydroxy-2-nonenal; SAG; apoptosis; cardiomyocytes; hypertrophy