Potential role of N-myristoyltransferase in pathogenic conditions

N-Myristoyltransferase (NMT) is the enzyme that catalyzes the covalent transfer of myristic acid to the N-terminal glycine residue of a protein substrate. In this review article, I summarize that NMT may have a potential role in cardiac muscle in the experimentally induced ischemia-reperfusion rat model and also in the streptozotoein-induced diabetic rat. 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. However. the localization of NMT is reversed by treatment with a calpain inhibitor (ALLM N-Ac-Leu-Leu-methioninal). During ischemia-reperfusion. the degradation of c-Src. which is a substrate of NMT. was observed. These findings suggested that the Src signaling may be impaired in ischemia-reperfusion owing to the altered localization of NMT from cytoplasm to nucleus. Streptozotocin-induced diabetes (an animal model for insulin-dependent diabetes mellitus) resulted in a 2.0-fold increase in rat liver NMT activity as compared with control animals. In obese (fa/fa) Zucker rats (an animal model for non-insulin-dependent diabetes mellitus). there was an similar to4.7-fold lower liver particulate NMT activity as compared with control lean rat livers. Administration of sodium orthovanadate to the diabetic rats normalized liver NMT activity. These results would indicate that rat liver particulate NMT activity appears to be inversely proportional to the level of plasma insulin. implicating insulin in the control of N- myristoylation. These are the first studies demonstrating the role of NMT in the pathogenesis of ischemia-reperfusion and diabetes mellitus. These conditions remain an important area of investigation.