This application is directed towards the study of the role of GLUT1 in the prevention of apoptosis induced by hypoxia in vascular smooth muscle cells. Hypoxia and ischemia have been shown to cause apoptosis in a number of different cell type. The principal investigator has demonstrated that vascular smooth muscle cells undergo apoptosis during hypoxia or after treatment with metabolic inhibitors, the same conditions that stimulate expression of the facilitative glucose transporter, GLUT1. The principal investigator has also demonstrated that over-expression of GLUT 1 prevents hypoxia-induced cell death in these cells by the prevention of apoptosis. Along with the prevention of apoptosis, over-expression of GLUT1 prevented the hypoxia- induced signaling through the stress activated protein kinase cascade but did not affect other mitogen in these cells raising the possibility that the protects effects of GLUT1 was through its effects on stress-activated protein kinase. Over-expression of GLUT1 attenuated the increases intracellular calcium induced by hypoxia. The underlying hypothesis in this application is that GLUT1 over-expression protects vascular smooth muscle cells from apoptosis by reducing activation of the SAPK pathway in conjunction by the reduction of intracellular calcium.
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