Document Detail

Antiapoptotic and antiautophagic effects of glial cell line-derived neurotrophic factor and hepatocyte growth factor after transient middle cerebral artery occlusion in rats.
MedLine Citation:
PMID:  20175208     Owner:  NLM     Status:  MEDLINE    
Glial cell line-derived neurotrophic factor (GDNF) and hepatocyte growth factor (HGF) are strong neurotrophic factors, which function as antiapoptotic factors. However, the neuroprotective effect of GDNF and HGF in ameliorating ischemic brain injury via an antiautophagic effect has not been examined. Therefore, we investigated GDNF and HGF for changes of infarct size and antiapoptotic and antiautophagic effects after transient middle cerebral artery occlusion (tMCAO) in rats. For the estimation of ischemic brain injury, the infarct size was calculated at 24 hr after tMCAO by HE staining. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) was performed for evaluating the antiapoptotic effect. Western blot analysis of microtubule-associated protein 1 light chain 3 (LC3) and immunofluorescence analysis of LC3 and phosphorylated mTOR/Ser(2448) (p-mTOR) were performed for evaluating the antiautophagic effect. GDNF and HGF significantly reduced infarct size after cerebral ischemia. The amounts of LC3-I plus LC3-II (relative to beta-tubulin) were significantly increased after tMCAO, and GDNF and HGF significantly decreased them. GDNF and HGF significantly increased p-mTOR-positive cells. GDNF and HGF significantly decreased the numbers of TUNEL-, LC3-, and LC3/TUNEL double-positive cells. LC3/TUNEL double-positive cells accounted for about 34.3% of LC3 plus TUNEL-positive cells. This study suggests that the protective effects of GDNF and HGF were greatly associated with not only the antiapoptotic but also the antiautophagic effects; maybe two types of cell death can occur in the same cell at the same time, and GDNF and HGF are capable of ameliorating these two pathways.
Jingwei Shang; Kentaro Deguchi; Toru Yamashita; Yasuyuki Ohta; Hanzhe Zhang; Nobutoshi Morimoto; Ning Liu; Xuemei Zhang; Fengfeng Tian; Tohru Matsuura; Hiroshi Funakoshi; Toshikazu Nakamura; Koji Abe
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  88     ISSN:  1097-4547     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-06-14     Completed Date:  2010-10-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2197-206     Citation Subset:  IM    
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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MeSH Terms
Apoptosis / physiology*
Autophagy / physiology*
Brain / pathology,  physiopathology*
Glial Cell Line-Derived Neurotrophic Factor / metabolism*
Hepatocyte Growth Factor / metabolism*
Infarction, Middle Cerebral Artery / pathology,  physiopathology*
Intracellular Signaling Peptides and Proteins / metabolism
Intracellular Space / metabolism
Microtubule-Associated Proteins / metabolism
Protein-Serine-Threonine Kinases / metabolism
Rats, Wistar
Time Factors
Reg. No./Substance:
0/Glial Cell Line-Derived Neurotrophic Factor; 0/Intracellular Signaling Peptides and Proteins; 0/LC3 protein, rat; 0/Microtubule-Associated Proteins; 67256-21-7/Hepatocyte Growth Factor; EC 2.7.1.-/mTOR protein; EC Kinases

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