Deficiency of presenilin-1 increases calcium-dependent vulnerability of neurons to oxidative stress in vitro

J Neurochem. 2001 Aug;78(4):807-14. doi: 10.1046/j.1471-4159.2001.00478.x.

Abstract

We examined the function of presenilin-1 (PS1) on neuronal resistance to oxidative stress. CNS neurons cultured from PS1-deficient mice exhibited increased vulnerability to H2O2 treatment compared with those from wild-type mice. Antioxidants protected the cultured neurons against the oxidative stress. An intracellular calcium chelator, BAPTA AM, as well as an L-type voltage-dependent calcium channel blocker, nifedipine, rescued the neurons from H2O2-induced death, while an N-type voltage-dependent calcium channel blocker, omega-conotoxin, or calcium release blockers from ER stores, dantrolene and xestospongin C, failed to rescue them. Wild-type and PS1-deficient neurons showed comparable increases of cytoplasmic free calcium levels after exposure to H2O2. Taken together with the data that PS1-deficient neurons exhibited increased vulnerability to glutamate, these findings imply that PS1 confers resistance to oxidative stress on neurons in calcium-dependent manners.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Animals
  • Calcium / metabolism*
  • Cell Survival
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Chelating Agents / pharmacology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Glutamic Acid / pharmacology
  • Hippocampus / cytology
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Oxidative Stress*
  • Peroxides / pharmacology
  • Presenilin-1

Substances

  • Chelating Agents
  • Membrane Proteins
  • PSEN1 protein, human
  • Peroxides
  • Presenilin-1
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Glutamic Acid
  • Egtazic Acid
  • Calcium