Leptin Suppresses Glutamate-Induced Apoptosis Through Regulation of ERK1/2 Signaling Pathways in Rat Primary Astrocytes
- 주제(키워드) Leptin , Glutamate , ERK1/2 , Astrocytes
- 주제(기타) Cell Biology; Physiology
- 설명문(일반) [Park, Hyunju; Ahn, So-Hee; Jung, Yieun; Choi, Youn-Hee] Ewha Womans Univ, Sch Med, Tissue Injury Def Res Ctr, Dept Physiol, Seoul, South Korea; [Yoon, Joo Chun] Ewha Womans Univ, Sch Med, Dept Microbiol, Seoul, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 KARGER
- 발행년도 2017
- URI http://www.dcollection.net/handler/ewha/000000151647
- 본문언어 영어
- Published As http://dx.doi.org/10.1159/000485950
초록/요약
Background/Aims: Leptin is a hormone expressed by adipose tissue that regulates body energy homeostasis and weight loss by activating leptin receptors in the hypothalamus. Leptin receptors are also expressed in astrocytes. An anti-apoptosis effect of leptin in brain has recently been reported. However, the anti-apoptosis mechanism of leptin in the brain is unknown. Methods: To investigate whether leptin exerts protective effects against glutamate-induced apoptosis in astrocytes, we performed cell viability assays and apoptosis assays using rat primary astrocytes. Intracellular signaling pathways involved in anti-apoptosis effects of leptin were analyzed by immunoblotting together with a leptin mutant (S120A/T121A) with antagonist function and pharmacological inhibitors. Results: We found that glutamate-induced apoptosis in rat primary astrocytes was significantly decreased by treatment with leptin. Leptin inhibited glutamate-induced phosphorylation of ERK1/2 in astrocytes. The leptin S120A/T121A mutant did not inhibit glutamate-induced ERK1/2 phosphorylation and ERK1/2-mediated apoptosis. Conclusions: Collectively, our results provide initial evidence that leptin exerts an anti-apoptotic effect against glutamate toxicity through activation of intracellular signaling pathways which reverse glutamate-induced ERK1/2 phosphorylation in primary astrocytes. Therefore, our findings suggest that leptin might be considered a candidate for potential therapeutic applications in glutamate-induced brain excitotoxicity. (C) 2017 The Author(s) Published by S. Karger AG, Basel
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