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Sensitive to apoptosis gene (SAG) is a novel RING finger protein that has been shown to be involved in protection against apoptotic cell death induced by oxidative stress in various cell types. As SAG has been previously shown to be expressed in the heart, we assessed its role in cardiac myocytes exposed to ischaemic stress. SAG expression was enhanced by hypoxia in neonatal cardiomyocytes as well as in the intact heart exposed to ischaemia/reperfusion. SAG levels remain elevated during the first 4 h of reoxygenation and return to control levels after 16 h of reoxygenation. We also show that overexpression of SAG in cardiac myocytes is able to protect against simulated ischaemia/reperfusion-induced apoptotic cell death. However, abrogation of the RING finger of the protein eliminates the anti-apoptotic properties of SAG. Furthermore, an antisense SAG construct enhances cell death, both in normoxic and hypoxic conditions. Hence, we conclude that SAG is a cardioprotective agent in cardiac cells exposed to ischaemic stress and an important protein involved in cardiomyocyte survival.

Type

Journal article

Journal

J Mol Cell Cardiol

Publication Date

03/2003

Volume

35

Pages

257 - 264

Keywords

Amino Acid Motifs, Animals, Apoptosis, Cell Cycle Proteins, Cell Hypoxia, Cells, Cultured, Myocardial Ischemia, Myocardial Reperfusion Injury, Myocytes, Cardiac, RNA-Binding Proteins, Rats, Rats, Sprague-Dawley