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1 CARDIOVASCULAR RESEARCH CENTER, University ofConnecticut School of Medicine, FARMINGTON, CT, USA; Pharmacology, University of Debresen, Debresen, Hungary
2 Medicine, Long Island Jewish Medical Center, New Hyde Park, NY, USA
3 Research, Malaysian Palm Oil Board, Kuala Lumpur, Malaysia
4 Pharmacology, University of Debresen, Debresen, Hungary
5 CARDIOVASCULAR RESEARCH CENTER, University ofConnecticut School of Medicine, FARMINGTON, CT, USA
* To whom correspondence should be addressed. E-mail: DDAS{at}NEURON.UCHC.EDU.
Tocotrienols, isomers of vitamin E, have been found to possess many health benefits. The present study was designed to determine if tocotrienol possess any direct cardioprotective role. Isolated rat hearts were perfused for 15 min with Krebs Ringer bicarbonate (KHB) buffer in the absence or presence of palm tocotrienol derived from tocotrienol rich fraction (0.035%) of palm oil (TRF). In another group of studies, the hearts were preperfused for 15 min in the presence of a cSrc inhibitor, PPI. The hearts were then subjected to 30 min of global ischemia followed by 2 h of reperfusion. As expected, ischemia/reperfusion caused ventricular dysfunction, electrical rhythm disturbances and increased myocardial infarct size. Either PPI or TRF could reverse the ischemia/reperfusion-mediated cardiac dysfunction. Ischemia/ reperfusion also upregulated cSrc expression and its phosphorylation. While TRF only minimally affected cSrc expression, it significantly inhibited the phosphorylation of cSrc. Ischemia/reperfusion reduced both 20S- and 26S- proteasome activities, an effect prevented by TRF pretreatment.. In contrast, PPI exerted a cardioprotective effect that is not mediated by the proteasome but rather through direct inhibition of cSrc. The results of this study support a role of cSrc in postischemic cardiac injury and dysfunction and demonstrate direct cardioprotective effects of TRF The cardioprotective properties of TRF appear to be due to inhibition of cSrc activation and proteasome stabilization.
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