Gas6 rescues cortical neurons from amyloid beta protein-induced apoptosis

Neuropharmacology. 2002 Dec;43(8):1289-96. doi: 10.1016/s0028-3908(02)00333-7.

Abstract

Gas6, a product of the growth-arrest-specific gene 6, protects neurons from serum deprivation-induced apoptosis. Neuronal apoptosis is also caused by amyloid beta protein (Abeta), whose accumulation in the brain is a characteristic feature of Alzheimer's disease. Abeta induces Ca(2+) influx via L-type voltage-dependent calcium channels (L-VSCCs), leading to its neurotoxicity. In the present study, we investigated effects of Gas6 on Abeta-induced cell death in primary cultures of rat cortical neurons. Abeta caused neuronal cell death in a concentration- and time-dependent manner. Gas6 significantly prevented neurons from Abeta-induced cell death. Gas6 ameliorated Abeta-induced apoptotic features such as the condensation of chromatin and the fragmentation of DNA. Prior to cell death, Abeta increased influx of Ca(2+) into neurons through L-VSCCs. Gas6 significantly inhibited the Abeta-induced Ca(2+) influx. The inhibitor of L-VSCCs also suppressed Abeta-induced neuronal cell death. The present cortical cultures contained few non-neuronal cells, indicating that Gas6 affected the survival of neurons directly, but not indirectly via non-neuronal cells. In conclusion, we demonstrate that Gas6 rescues cortical neurons from Abeta-induced apoptosis. Furthermore, the present study indicates that inhibition of L-VSCC contributes to the neuroprotective effect of Gas6.

MeSH terms

  • Amyloid beta-Peptides / pharmacology*
  • Amyloid beta-Peptides / physiology
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Calcium / metabolism
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Intercellular Signaling Peptides and Proteins*
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Pregnancy
  • Proteins / pharmacology*
  • Proteins / physiology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Amyloid beta-Peptides
  • Intercellular Signaling Peptides and Proteins
  • Proteins
  • growth arrest-specific protein 6
  • Calcium