Taurine, which is found at high concentration in the heart, exerts several protective actions on myocardium. Physically, the high level of
taurine in heart is maintained by a
taurine transporter (TauT), the expression of which is suppressed under ischemic insult. Although
taurine supplementation upregulates TauT expression, elevates the intracellular
taurine content and ameliorates the ischemic injury of cardiomyocytes (CMs), little is known about the regulatory mechanisms of
taurine governing TauT expression under
ischemia. In this study, we describe the TonE (tonicity-responsive
element)/TonEBP (TonE-
binding protein) pathway involved in the
taurine-regulated TauT expression in ischemic CMs.
Taurine inhibited the
ubiquitin-dependent proteasomal degradation of TonEBP, promoted the translocation of TonEBP into the nucleus, enhanced TauT promoter activity and finally upregulated TauT expression in CMs. In addition, we observed that TonEBP had an anti-apoptotic and anti-oxidative role in CMs under
ischemia. Moreover, the protective effects of
taurine on
myocardial ischemia were TonEBP dependent. Collectively, our findings suggest that TonEBP is a core molecule in the protective mechanism of
taurine in CMs under ischemic insult.