Biomedical subjects
Jasim M Radhi
Publications and source records attributed to Jasim M Radhi.
Altered expression and localization of N-myristoyltransferase in experimentally induced rat model of ischemia-reperfusion.
N-myristoyltransferase (NMT) catalyzes the attachment of myristate onto the amino-terminal glycine residue of select polypeptides. In the present study, we investigated the expression and activity of NMT in rat heart after ischemia and reperfusion. Western blot analysis of rat heart samples indicated a prominent immunoreactive band of 66 kDa probed with human NMT antibody. Both the expression and activity of NMT were increased by ischemia-reperfusion. Immunohistochemical studies showed cytosolic localization of NMT in normal rat heart and predominant nuclear localization after ischemia followed by reperfusion. The pre-ischemic perfusion and post-ischemic reperfusion of hearts with a cell-permeable calpain inhibitor (N-Ac-Leu-Leu-methioninal) suppressed the increase in calpain expression and reversed the localization of NMT from nucleus to cytoplasm. This is the first study demonstrating the expression and alteration of NMT localization in cardiac ischemia and pertaining to a possible role of co-translational modification of proteins in cardiac functions and injury.
Calmodulin-dependent cyclic nucleotide phosphodiesterase in an experimental rat model of cardiac ischemia-reperfusion.
In the present study, we investigated the activity and expression of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) and the effects of calpains in rat heart after ischemia and reperfusion. Immunohistochemical studies indicated that CaMPDE in normal heart is localized in myocardial cells. Rat ischemic heart showed a decrease in CaMPDE activity in the presence of Ca2+ and calmodulin; however, in ischemic-reperfusion tissue a progressive increase in Ca2+ and calmodulin-independent cyclic nucleotide phosphodiesterase (CaM-independent PDE) activity was observed. Perfusion of hearts with cell-permeable calpain inhibitor suppressed the increase of Ca2+ and CaM-independent PDE activity. Protein expression of CaMPDE was uneffected by hypoxic injury to rat myocardium. The purified heart CaMPDE was proteolyzed by calpains into a 45 kDa immunoreactive fragment in vitro. Based on these results, we propose that hypoxic injury to rat myocardium results in the generation of CaM-independent PDE by calpain mediated proteolysis, allowing the maintenance of cAMP concentrations within the physiological range.