Induction of ischemic tolerance in rat cortical neurons by 3-nitropropionic acid: chemical preconditioning.
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.
Weih
M
M
Department of Neurology, Charité, Berlin, Germany. markus.weih@charite.de
Bergk
A
A
Isaev
N K
NK
Ruscher
K
K
Megow
D
D
Riepe
M
M
Meisel
A
A
Victorov
I V
IV
Dirnagl
U
U
Dirnagi
U
U
D000818:Animals; D001711:Biotransformation / Q000187:drug effects / Q000502:physiology; D002545:Brain Ischemia / Q000235:genetics / Q000473:pathology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019194:Ischemic Preconditioning; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009574:Nitro Compounds; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C497444:Hif1a protein, rat; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D009574:Nitro Compounds; D009687:Nuclear Proteins; D011422:Propionates; D014157:Transcription Factors; D013385:Succinate Dehydrogenase; C015392:3-nitropropionic acid