Regulated Hypoxia/Reperfusion-Dependent Modulation of ERK1/2, cPLA2, and Bcl-2/Bax: A Potential Mechanism of Neuroprotective Effect of Penehyclidine Hydrochloride

The activation of event-related kinase 1/2 (ERK1/2) and cytosolic phospholipaseA(2) (cPLA(2)), which can aggravate hypoxia/reoxygenation (H/R) damage related to their downstream Bcl-2/Bax and Caspase-3 pathway, plays a key role in H/R. The M-1 receptors could be responsible for activation of ERK1/2. Thus, it seems that the regulation of M-1 receptors mediated the ERK1/2; cPLA(2)-mediated Bcl-2/Bax pathway may be a significant responsive signal in H/R. Penehyclidine hydrochloride (PHC) is an anticholinergic agent with high degree of selectivity for M-1 and M-3 receptor subtypes, it is reported that PHC has a protective effect against H/R damage. Here we hypothesize and demonstrate that PHC could downregulate the expression of pERK1/2, cPLA(2), and Caspase-3, increased the ratio of Bcl-2/Bax. This study may widen the application of PHC and therapeutic agents of stroke.