Leptin Suppresses Glutamate-Induced Apoptosis Through Regulation of ERK1/2 Signaling Pathways in Rat Primary Astrocytes
Autor: | So-Hee Ahn, Yieun Jung, Joo Chun Yoon, Youn Hee Choi, Hyunju Park |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Leptin Cell Survival MAP Kinase Signaling System Physiology Excitotoxicity Glutamic Acid Adipose tissue Apoptosis medicine.disease_cause Energy homeostasis lcsh:Physiology Rats Sprague-Dawley lcsh:Biochemistry 03 medical and health sciences medicine Animals lcsh:QD415-436 Phosphorylation Cells Cultured Leptin receptor ERK1/2 lcsh:QP1-981 Chemistry digestive oral and skin physiology Glutamate receptor Rats Cell biology 030104 developmental biology Hypothalamus Astrocytes Glutamate hormones hormone substitutes and hormone antagonists |
Zdroj: | Cellular Physiology and Biochemistry, Vol 44, Iss 6, Pp 2117-2128 (2017) |
ISSN: | 1421-9778 1015-8987 |
Popis: | 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. |
Databáze: | OpenAIRE |
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