Mitochondrial Dysfunction Caused By Chronic Intermittent Hypoxia And Drug Intervention

Part OneEffects of Vitamin E and L-3-n-Butylphathalide on the Release of Cytochrome C and Activation of Caspase-3 Induced by Chronic Episodic HypoxiaBackground: It has been proved that chronic episodic hypoxia(EHYP) can induce apoptosis.Apoptosis is an active mode of death, which was originally defined morphologically by the characteristic shrinkage, membrane blebbing ,chromatin condensation and nuclear fragmentation of cells dying by this process. The biochemical pathways to apoptosis are rapidly being uncovered ,revealing that it is a highly regulated process. This is in contrast to necrosis ,which is typified by cell swelling and uncontrolled lysis.The mechanism of apoptosis is not clearly understood .It has been proposed that oxidative stress, calcium overload and mitochondrial dysfunction might be involved in the process of apoptosis .During recent years,the participation of mitochondria in the mechanism of apoptosis has received much attention in recent years .The Bcl-2 family proteins could regulate the mitochondrial permeability transition ,and /or the release of apoptogenic proteins,such as cytochrome c ,to the cytoplasm where it activates caspase-3, which has been reported to trigger apoptosis.Animal models of EHYP are not so often used as models of ischemia/hypoxia when researchers study the mechanism of apoptosis. The pharmacological research about Vitamin E (VitE) and L-3-n-butylphathalide (L-NBP) implies that VitE can scavenge oxygen free radicals and inhibit lipid peroxidation and that L-NBP can suppress cytochrome c release and activation of caspase-3 induced by cerebral ischemia .Given these considerations ,we hypothesize that VitE and L-NBP can ameliorate the release of cytochrome c and the activation of caspase- 3 induced by EHYP.