Induction of ischemic tolerance in rat cortical neurons by 3-nitropropionic acid: chemical preconditioning

Neurosci Lett. 1999 Sep 17;272(3):207-10. doi: 10.1016/s0304-3940(99)00594-7.

Abstract

Sublethal ischemia leads to increased tolerance against subsequent ischemia. We investigated whether tolerance could also be elicited by mild respiratory-chain inhibition (chemical hypoxia) in a rat neuronal-cell enriched culture system. 3-Nitropropionic acid (3-NPA) caused a concentration-dependent inhibition of succinate-dehydrogenase. Two hours preconditioning with 3-NPA 24-48 h before oxygen-glucose deprivation (OGD) reduced neuronal damage morphologically and reduced lactate deydrogenase (LDH) release up to 72% compared to sham-treated sister cultures without 3-NPA. In an attempt to elucidate transcriptional mechanisms, we found no rapid translocation of the hypoxia-sensitive transcription factors N F-KB or hypoxia-inducible factor-I (HIF-I) at 3-NPA concentrations sufficient to trigger tolerance against OGD. In accordance to previous in vivo and brain slice data, we conclude that 3-NPA chemically induces tolerance against oxygen-glucose deprivation in vitro. However, the underlying mechanisms remain elusive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotransformation / drug effects
  • Biotransformation / physiology
  • Brain Ischemia / genetics
  • Brain Ischemia / pathology*
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / pathology*
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Circulation / physiology
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • Enzyme Inhibitors / pharmacology*
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ischemic Preconditioning*
  • NF-kappa B / biosynthesis
  • NF-kappa B / genetics
  • Neurons / drug effects
  • Neurons / pathology*
  • Nitro Compounds
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics
  • Propionates / pharmacology*
  • Rats
  • Succinate Dehydrogenase / antagonists & inhibitors
  • Succinate Dehydrogenase / metabolism
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Transcription, Genetic

Substances

  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • NF-kappa B
  • Nitro Compounds
  • Nuclear Proteins
  • Propionates
  • Transcription Factors
  • Succinate Dehydrogenase
  • 3-nitropropionic acid