L-3-n-butyl-phthalide alleviates hydrogen peroxide-induced apoptosis by PKC pathway in human neuroblastoma SK-N-SH cells.

摘要

Alzheimer's disease (AD) is the most common form of dementia. Oxidative stress is one of the earliest events in the neurological and pathological changes of AD. L-3-n-butyl-phthalide (L-NBP), an anti-cerebral ischemia agent, has been shown a potential in AD treatment. In this study, we investigated the neuroprotective effect of L-NBP on hydrogen peroxide (HO)-induced apoptosis in human neuroblastoma SK-N-SH cells. HO significantly reduced cell viability and increased the number of apoptotic-like cells, indicating that HO induced neurotoxicity. In addition, real-time PCR and western blot studies showed that Bcl-2 and Bcl-w expressions were decreased, and Bax expression was increased with HO treatment. Moreover, protein kinase C (PKC) alpha expression was down-regulated after HO treatment. All of these phenotypes induced by HO were markedly reversed by L-NBP. Pretreatment with L-NBP significantly increased cell viability of HO-damaged cells, and reduced HO-induced neuronal apoptosis. L-NBP treatment at dose of 10 muM inhibited HO-induced down-regulation of Bcl-2, Bcl-w, and PKCalpha but also attenuated the overexpression of Bax. PKC inhibitor, calphostin C, significantly attenuated the protective effects of L-NBP. Our findings suggest that L-NBP may protect neurons against HO-induced apoptosis by modulating apoptosis-related genes and activating PKCalpha pathway.