Referenced in: none

Automatically associated channels: TRP , TRPC , TRPC1

Title: SKF-96365 attenuates toxin-induced neuronal injury through opposite regulatory effects on Homer1a and Homer1b/c in cultured rat mesencephalic cells.

Authors: Xuan Zeng, Zhi-Guo Pan, Yu Shao, Xiao-Na Wu, Shen-Xi Liu, Nan-Lin Li, Wei-Min Wang

Journal, date & volume: Neurosci. Lett., 2013 May 24 , 543, 183-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23567742

Abstract
Disturbances in Ca(2+) homeostasis have been implicated in a variety of neuro-pathological conditions including Parkinson's disease (PD). In the present study, we investigated the potential protective effect of SKF-96365, an originally identified blocker of receptor-mediated calcium entry, on MPP(+) induced neuronal injury in cultured rat mesencephalic cells. We found that pretreatment with SKF-96365 30 min before injury significantly reduced nuclear damage, decreased LDH release and inhibited apoptotic neuronal death. The results of calcium image also showed that SKF-96365 inhibited the increase of intracellular calcium induced by MPP(+), which was not dependent on the expression and function of TRPC1. In addition, SKF-96365 increased the expression of Homer1a, but decreased the expression of Homer1b/c in the presence or absence of MPP(+). Furthermore, overexpression of Homer1a by using recombinant lentivirus and knockdown of Homer1b/c by short interfering RNA (siRNA) further enhanced protective effects of SKF-96365 against MPP(+) injury. Taken together, these data suggest that SKF-96365 protects cultured rat mesencephalic cells against MPP(+) induced cytotoxicity, and this protection may be at least in part dependent on attenuating intracellular calcium overload, opposite regulatory effects on Homer1a and Homer1b/c expressions.