Adipose stem cells-conditioned medium blocks 6-hydroxydopamine-induced neurotoxicity via the IGF-1/PI3K/AKT pathway

Neurosci Lett. 2014 Oct 3:581:98-102. doi: 10.1016/j.neulet.2014.08.033. Epub 2014 Aug 23.

Abstract

Previous studies suggest that the delivery of neurotrophic factors secreted from adipose stromal cells (ASC) protect the brain from 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. However, it remains unclear which secreted neurotrophic factor has an important role in protecting 6-OHDA-treated neurons. Through the use of antibodies in this study, we demonstrated that specific neutralization of IGF-1 activity in ASC conditioned media (ASC-CM) significantly blocks ASC-CM-induced neuroprotection against 6-OHDA neurotoxicity. Consistently, this neuroprotection was mostly attributed to the activation of the AKT-mediated signaling pathway. In contrast, brain derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in ASC-CM did not play a role in ASC-CM-induced neuroprotection against 6-OHDA.

Keywords: 6-hydroxydopamine; AKT; ASC-CM; IGF-1; Neuronal cell death.

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Animals
  • Antibodies
  • Apoptosis
  • Cell Survival
  • Humans
  • Insulin-Like Growth Factor I / immunology
  • Insulin-Like Growth Factor I / metabolism*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • Oxidopamine / toxicity*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats, Sprague-Dawley
  • Signal Transduction*
  • Stromal Cells / cytology
  • Stromal Cells / metabolism*

Substances

  • Antibodies
  • Intercellular Signaling Peptides and Proteins
  • Insulin-Like Growth Factor I
  • Oxidopamine
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt