BAG-1L Protects SH-SY5Y Neuroblastoma Cells Against Hypoxia/Re-oxygenation Through Up-Regulating HSP70 and Activating PI3K/AKT Signaling Pathway

Neurochem Res. 2017 Oct;42(10):2861-2868. doi: 10.1007/s11064-017-2304-y. Epub 2017 May 18.

Abstract

BCL-2-associated athanogene-1(BAG-1) is a multifunctional and anti-apoptotic protein that was first identified as a binding partner of BCL-2. But the effects and mechanisms for BAG-1 against hypoxic damage is unclear up to now. Whether BAG-1 could protect the human brain against hypoxic damage through up-regulating 70 kDa heat shock proteins (HSP70) and PI3K/AKT pathway activation? In present study, we examined the changes of HSP70 and AKT and p-AKT protein level in SH-SY5Y cells with BAG-1L gene over-expression subjected to hypoxia/re-oxygenation injury. BAG-1L over-expression increased neuronal viability, and it reduced apoptosis of neurons after hypoxia/re-oxygenation for 8 h. BAG-1L over-expression enhanced the HSP70 protein levels and increased p-AKT/total AKT ratio after hypoxia/re-oxygenation for 8 h. These results suggest that BAG-1L over-expression protects against hypoxia/re-oxygenation injury, at least in part, by interacting with HSP70, and by accelerating the activation of PI3K/AKT pathways.

Keywords: Anti-apoptotic effect; BAG-1L gene; HSP70; Hypoxia; PI3K/AKT pathway.

MeSH terms

  • Apoptosis / drug effects
  • Cell Hypoxia
  • Cell Line, Tumor
  • DNA-Binding Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • Neuroblastoma / metabolism
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • Transcription Factors / metabolism*
  • Transcriptional Activation / drug effects

Substances

  • BCL2-associated athanogene 1 protein
  • DNA-Binding Proteins
  • HSP70 Heat-Shock Proteins
  • Neuroprotective Agents
  • Transcription Factors
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt