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SKF-96365 Attenuates Toxin-Induced Neuronal Injury Through Opposite Regulatory Effects on Homer1a and Homer1b/c in Cultured Rat Mesencephalic Cells

SKF-96365 Attenuates Toxin-Induced Neuronal Injury Through Opposite Regulatory Effects on Homer1a and Homer1b/c in Cultured Rat Mesencephalic Cells

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

Neurosci Lett. 2013 May 24;543:183-8.

PMID: 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP130495351	SKF-96365		130495-35-1	Price

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