Isoflurane preconditioning activates HIF-1alpha, iNOS and Erk1/2 and protects against oxygen-glucose deprivation neuronal injury.

Abstract

Preconditioning neurons with isoflurane, a commonly used volatile anesthetic in clinical practice, improves tolerance of subsequent ischemia in both intact animal models and in vitro preparations. To investigate the mechanisms of this protection, we primarily cultured rat hippocampal neurons and simulated ischemia in vitro by oxygen-glucose deprivation (OGD). Neuron viability was measured. Neuron injury was observed by inverted phase contrast microscope and assessed by lactate dehydrogenase (LDH) release. Gene expression was examined by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Isoflurane exposure for 2 h at 24 h before a 2 h OGD dose-dependently reduced cell injury. Isoflurane accumulated phosphorylation/activation of extracellular signal-related kinases 1 and 2 (Erk1/2) and hypoxia inducible factor (HIF)-1alpha, a transcription factor involved in cell survival. Inhibition of the phospho-Erk1/2 partially abolished the isoflurane preconditioning-induced HIF-1alpha protein content accumulation and neuroprotection. Isoflurane also increased inducible nitric oxide synthase (iNOS) mRNA levels, a downstream gene of HIF-1alpha. Thus, the current results indicate that isoflurane preconditioning activates HIF-1alpha during protection against OGD neuronal injury and the activation might be partly mediated by the Erk1/2 pathway.

• Authors: Qi-Fang Li, Ye-Sen Zhu, Hong Jiang
• Journal: Brain research (Brain Res) Vol. 1245 Pg. 26-35 (Dec 15 2008) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 18930717 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hypoxia-Inducible Factor 1, alpha Subunit
• RNA, Messenger
• Isoflurane
• L-Lactate Dehydrogenase
• Nitric Oxide Synthase Type II
• Extracellular Signal-Regulated MAP Kinases
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Glucose
• Oxygen

Topics

• Animals
• Animals, Newborn
• Blotting, Western
• Cell Hypoxia
• Cell Survival (drug effects, physiology)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Extracellular Signal-Regulated MAP Kinases (genetics, metabolism)
• Glucose (pharmacology)
• Hippocampus (cytology)
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
• Isoflurane (pharmacology)
• L-Lactate Dehydrogenase (metabolism)
• Microscopy, Phase-Contrast
• Mitogen-Activated Protein Kinase 1 (genetics, metabolism)
• Mitogen-Activated Protein Kinase 3 (genetics, metabolism)
• Neurons (cytology, drug effects, metabolism)
• Nitric Oxide Synthase Type II (genetics, metabolism)
• Oxygen (pharmacology)
• Phosphorylation (drug effects)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Wistar
• Reverse Transcriptase Polymerase Chain Reaction