Abstract

Vitamin E Regulates SMase Activity, GSH levels, and Inhibits Neuronal Death in Stroke-Prone Spontaneously Hypertensive Rats during Hypoxia and Reoxygenation

Author(s): Kazuo Yamagata, Shizuko Ichinose, Chika Tagawa and Motoki Tagami

Stroke-prone spontaneously hypertensive rats (SHRSP/IZM) develop severe hypertension, and more than 95% of them die of cerebral stroke, making them widely used as models of experimental cerebral ischemia. The neurons of SHRSP/IZM are more susceptible to hypoxia and reoxygenation (H/R) than those of Wistar Kyoto (WKY/IZM) rats. In particular, cerebral ischemia strongly induces neuronal death in SHRSP/IZM. We examined the effect of high dose vitamin E on the levels of glutathione (GSH) and cell death during H/R in neurons isolated from SHRSP/IZM and WKY/IZM rats. The neurons of SHRSP/IZM were more vulnerable and lost more GSH than those of the WKY/IZM rats. High dose vitamin E induced the expression of gamma glutamylcystenyl synthase (γ-GCS) mRNA, increased GSH levels, reduced neutral sphingomyelinase (N-SMase) activity, and strongly prevented neuronal death. The level of GSH was significantly lower in SHRSP/IZM than WKY/IZM neurons following exposure to hypoxia and H/R. On the other hand, the activity of N-SMase was increased in SHRSP/IZM compared to the WKY/IZM neurons. These results suggest the decrease in GSH levels of SHRSP/IZM neurons to be associated with neuronal vulnerability and that GSH, production of which is induced by a high dose of vitamin E.