Nuclear relocation of DGKζ in cardiomyocytes under conditions of ischemia/reperfusion

Abstract

Diacylglycerol (DG) and phosphatidic acid (PA) are generated under various conditions, such as ligand stimulation and several stresses. They serve as second messengers to respond to pathophysiological conditions. DG kinase (DGK) catalyzes DG to produce PA. It is regarded as a regulator of these lipid messengers. Previous studies show that DGKζ, a nuclear isozyme, translocates from the nucleus to the cytoplasm in hippocampal neurons under transient ischemia and never relocates to the nucleus after reperfusion. This study examined whether a similar phenomenon is observed in cardiomyocytes, which represent another type of postmitotic, terminally differentiated cell. We performed immunostaining on ischemic hearts induced by occlusion of the left anterior descending coronary artery and on primary cultured cardiomyocytes under oxygen-glucose deprivation (OGD). In the animal model, 10 min ischemia is sufficient to cause DGKζ to disappear from the nucleus in cardiomyocytes. However, DGKζ is observed again in the nucleus at 10 min following reperfusion after 10 min ischemia, which contrasts sharply with ischemic hippocampal neurons. Similar results were obtained from experiments using primary cultured cardiomyocytes under OGD conditions, except that DGKζ relocates autonomously, if at all, to the nucleus, even under continuous OGD conditions. Results suggest that DGKζ is involved in the acute phase of cellular response to ischemic stress in cardiomyocytes in a similar, but not identical, manner to that of neurons.