Antiapoptotic and antiautophagic effects of glial cell line-derived neurotrophic factor and hepatocyte growth factor after transient middle cerebral artery occlusion in rats

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

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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/Ser2448 (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 β-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.

Original languageEnglish
Pages (from-to)2197-2206
Number of pages10
JournalJournal of Neuroscience Research
Volume88
Issue number10
DOIs
Publication statusPublished - Aug 1 2010

Keywords

  • Apoptosis
  • Autophagy
  • Cerebral ischemia
  • GDNF
  • HGF

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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