Leptin Suppresses Glutamate-Induced Apoptosis Through Regulation of ERK1/2 Signaling Pathways in Rat Primary Astrocytes

Hyunju Park, So Hee Ahn, Yieun Jung, Joo Chun Yoon, Youn Hee Choi

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2117-2128
Number of pages12
JournalCellular Physiology and Biochemistry
Volume44
Issue number6
DOIs
StatePublished - 1 Jan 2018

Keywords

  • Astrocytes
  • ERK1/2
  • Glutamate
  • Leptin

Fingerprint

Dive into the research topics of 'Leptin Suppresses Glutamate-Induced Apoptosis Through Regulation of ERK1/2 Signaling Pathways in Rat Primary Astrocytes'. Together they form a unique fingerprint.

Cite this