title: Morphine Protects Spinal Cord Astrocytes from Glutamate-Induced Apoptosis via Reducing Endoplasmic Reticulum Stress.
abstract: Glutamate is not only a neurotransmitter but also an important neurotoxin in central nervous system (CNS). Chronic elevation of glutamate induces both neuronal and glial cell apoptosis. However, its effect on astrocytes is complex and still remains unclear. In this study, we investigated whether morphine, a common opioid ligand, could affect glutamate-induced apoptosis in astrocytes. Primary cultured astrocytes were incubated with glutamate in the presence/absence of morphine. It was found that morphine could reduce glutamate-induced apoptosis of astrocytes. Furthermore, glutamate activated Ca2+release, thereby inducing endoplasmic reticulum (ER) stress in astrocytes, while morphine attenuated this deleterious effect. Using siRNA to reduce the expression of κ-opioid receptor, morphine could not effectively inhibit glutamate-stimulated Ca2+release in astrocytes, the protective effect of morphine on glutamate-injured astrocytes was also suppressed. These results suggested that morphine could protect astrocytes from glutamate-induced apoptosis via reducing Ca2+overload and ER stress pathways. In conclusion, this study indicated that excitotoxicity participated in the glutamate mediated apoptosis in astrocytes, while morphine attenuated this deleterious effect via regulating Ca2+release and ER stress.
authors: Department of Forensic Medicine, Shanxi Medical University, 56 South Xinjian Road, Taiyuan 030001, China. zc_sxmu88@163.com.
authors: Chao
authors: C
authors: Zhang
authors: Department of Nephrology, People's Hospital of Shanxi Province, 29 Shuang-ta Street, Taiyuan 030012, China. cd_wang138@163.com.
authors: Chendan
authors: C
authors: Wang
authors: Department of Forensic Medicine, Shanxi Medical University, 56 South Xinjian Road, Taiyuan 030001, China. j_happy317@126.com.
authors: Jianbo
authors: J
authors: Ren
authors: Department of Forensic Medicine, Shanxi Medical University, 56 South Xinjian Road, Taiyuan 030001, China. xiangjieguo1980@yeah.net.
authors: Xiangjie
authors: X
authors: Guo
authors: Department of Forensic Medicine, Shanxi Medical University, 56 South Xinjian Road, Taiyuan 030001, China. kmyun2000@163.com.
authors: Keming
authors: K
authors: Yun
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D009020:Morphine
keywords: apoptosis; astrocytes; endoplasmic reticulum; glutamate; morphine