Huperzine A attenuates hydrogen peroxide-induced apoptosis by regulating expression of apoptosis-related genes in rat PC12 cells

The present studies investigated effects of huperzine A (HupA), a selective acetylcholinesterase (AChE) inhibitor and promising anti-dementia agent, O n hydrogen peroxide (H2O2)-induced apoptosis and the expression of apoptosi s-related genes in rat pheochromocytoma line PC12 cells. Transient exposure of the cells to H2O2 (100 muM) triggered a typical apoptosis as evidenced by chromatin condensation, nuclei fragmentation and DNA laddering. RT-PCR s tudies showed up-regulated p53 and Bax but lowered Bcl-2 mRNA levels with H 2O2 treatment. The results were further confirmed at protein levels by immu nocytochemistry with specific antibodies. Preincubation with HupA (1 muM) s ignificantly prevented the cells from apoptosis, attenuated H2O2-induced ov er-expression of Bax and p53, and rehabilitated the level of Bcl-2. The pre sent findings suggest that HupA exerts significant protection against H2O2- induced apoptosis, possibly through improving expression of apoptosis-relat ed genes. NeuroReport 12:2629-2634 (C) 2001 Lippincott Williams & Wilkins.