Glial cell line-derived neurotrophic factor protects astrocytes from staurosporine- and ischemia- induced apoptosis.
Glial cell line-derived neurotrophic factor (GDNF) promotes the survival and functions of neurons. It has been shown to be a promising candidate in the treatment of ischemia and other neurodegenerative diseases. We transfected mouse astrocytes in primary cultures with a human GDNF gene and found that their conditioned medium could not only support the growth and survival of cultured dopaminergic neurons but also protect astrocytes from staurosporine- and ischemia-induced apoptosis. This indicated that these transfected astrocytes could release GDNF. A similar protective effect on astrocytes against apoptosis was evident when recombinant human GDNF was used. Moreover, GDNF reduced caspase-3 activity but not that of caspase-1 in cultured astrocytes after ischemia treatment. Thus, GDNF protects astrocytes from apoptosis by inhibiting the activation of caspase-3.
Yu
Albert Cheung Hoi
AC
Neuroscience Research Institute, Peking University, Beijing, China. achy@bjmu.edu.cn
Liu
Rong Yu
RY
Zhang
Yun
Y
Sun
Hao Rui
HR
Qin
Lu Ye
LY
Lau
Lok Ting
LT
Wu
Bing Yi
BY
Hui
Hung Kit
HK
Heung
Man Yeung
MY
Han
Ji Sheng
JS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000633:toxicity; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007511:Ischemia / Q000503:physiopathology; D051379:Mice; D008813:Mice, Inbred ICR; D019311:Staurosporine / Q000633:toxicity; D014162:Transfection
D004791:Enzyme Inhibitors; D051100:Glial Cell Line-Derived Neurotrophic Factor; D053148:Caspase 3; D019311:Staurosporine