Hsp20 Protects against Oxygen-Glucose Deprivation/Reperfusion-Induced Golgi Fragmentation and Apoptosis through Fas/FasL Pathway

Oxid Med Cell Longev. 2015:2015:606934. doi: 10.1155/2015/606934. Epub 2015 Jun 24.

Abstract

Cerebral ischemia-reperfusion injury plays an important role in the development of tissue injury after acute ischemic stroke. Finding effective neuroprotective agents has become a priority in the treatment of ischemic stroke. The Golgi apparatus (GA) is a pivotal organelle and its protection is an attractive target in the treatment of cerebral ischemia-reperfusion injury. Protective effects of Hsp20, a potential cytoprotective agent due to its chaperone-like activity and involvement in regulation of many vital processes, on GA were assessed in an ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces Golgi fragmentation, apoptosis, and p115 cleavage in N2a cells. However, transfection with Hsp20 significantly attenuates OGDR-induced Golgi fragmentation and apoptosis. Hsp20 interacts with Bax, decreases FasL and Bax expression, and inhibits caspases 3 and p115 cleavage in N2a cells exposed to OGDR. Our data demonstrate that increased Hsp20 expression protects against OGDR-induced Golgi fragmentation and apoptosis, likely through interaction with Bax and subsequent amelioration of the OGDR-induced elevation in p115 cleavage via the Fas/FasL signaling pathway. This neuroprotective potential of Hsp20 against OGDR insult and the underlying mechanism will pave the way for its potential clinical application for cerebral ischemia-reperfusion related disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Fas Ligand Protein / metabolism*
  • Glucose / deficiency*
  • Golgi Apparatus / metabolism*
  • Golgi Matrix Proteins
  • HSP20 Heat-Shock Proteins / genetics
  • HSP20 Heat-Shock Proteins / metabolism*
  • Mice
  • Oxygen / metabolism*
  • Signal Transduction
  • Vesicular Transport Proteins / metabolism
  • bcl-2-Associated X Protein / metabolism
  • fas Receptor / metabolism*

Substances

  • Fas Ligand Protein
  • Fas protein, mouse
  • Fasl protein, mouse
  • Golgi Matrix Proteins
  • HSP20 Heat-Shock Proteins
  • Vesicular Transport Proteins
  • bcl-2-Associated X Protein
  • fas Receptor
  • vesicular transport factor p115
  • Caspase 3
  • Glucose
  • Oxygen