title: Regulated hypoxia/reperfusion-dependent modulation of ERK1/2, cPLA2, and Bcl-2/Bax: a potential mechanism of neuroprotective effect of penehyclidine hydrochloride.
abstract: The activation of event-related kinase 1/2 (ERK1/2) and cytosolic phospholipaseA2 (cPLA2), 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 M1 receptors could be responsible for activation of ERK1/2. Thus, it seems that the regulation of M1 receptors mediated the ERK1/2; cPLA2-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 M1 and M3 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, cPLA2, and Caspase-3, increased the ratio of Bcl-2/Bax. This study may widen the application of PHC and therapeutic agents of stroke.
authors.affiliation: Department of Pharmacology, XuZhou Medical College, XuZhou, Jiangsu, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Tengfei
authors.initials: T
authors.lastname: Ma
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Sun
authors.forename: Yigang
authors.initials: Y
authors.lastname: Wang
authors.forename: Shuling
authors.initials: S
authors.lastname: Gu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D000860:Hypoxia / Q000188:drug therapy / Q000378:metabolism*; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D058632:Neuroprostanes / Q000494:pharmacology* / Q000627:therapeutic use; D054510:Phospholipases A2, Cytosolic / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011812:Quinuclidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion / Q000379:methods; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D003517:Cyclopentanes; D058632:Neuroprostanes; D019253:Proto-Oncogene Proteins c-bcl-2; D011812:Quinuclidines; D051028:bcl-2-Associated X Protein; C066419:3-(2'-phenyl-2'-cyclopentyl-2'-hydroxyethoxy)quinuclidine; D054510:Phospholipases A2, Cytosolic; D053148:Caspase 3