Isoflurane preconditioning increases B-cell lymphoma-2 expression and reduces cytochrome c release from the mitochondria in the ischemic penumbra of rat brain.

Abstract

We and others have shown that prior exposure to the volatile anesthetic isoflurane induces ischemic tolerance in the brain. Our results also suggest that isoflurane preconditioning reduces cell apoptosis in the penumbral region of rat brain. We designed this study to determine whether isoflurane preconditioning decreased mitochondria-dependent cell apoptosis. Adult male Sprague-Dawley rats were exposed to or not exposed to 2% isoflurane for 30 min at 24 h before the permanent middle cerebral arterial occlusion. Western blotting was used to quantify protein expression in the cytosolic and mitochondrial fractions of non-ischemic brain cortex and brain cortex in the ischemic core and penumbra. Isoflurane preconditioning significantly decreased the infarct volume of cerebral cortex and improved neurological outcome. Isoflurane increased the expression of the antiapoptotic B-cell lymphoma-2 (Bcl-2) proteins in the cerebral cortex of rats without brain ischemia. Rats preconditioned with isoflurane before brain ischemia had increased Bcl-2 expression in the penumbra. Isoflurane preconditioning reduced the release of cytochrome c from the mitochondria and the activation of caspase 3 in the penumbra. However, isoflurane preconditioning did not alter the translocation of Bid and Bax from the cytosol to the mitochondria, identified mechanisms for Bcl-2 to block the release of cytochrome c from the mitochondria. Our results suggest that isoflurane preconditioning increases Bcl-2 expression to block the release of cytochrome c from the mitochondria to decrease the cell apoptosis in the penumbra.

• Authors: Liaoliao Li, Longyun Peng, Zhiyi Zuo
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 586 Issue 1-3 Pg. 106-13 (May 31 2008) ISSN: 0014-2999 [Print] Netherlands
• PMID: 18355806 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anesthetics, Inhalation
• BH3 Interacting Domain Death Agonist Protein
• Neuroprotective Agents
• bcl-2-Associated X Protein
• Cytochromes c
• Isoflurane
• Caspase 3

Topics

• Anesthetics, Inhalation (pharmacology)
• Animals
• BH3 Interacting Domain Death Agonist Protein (metabolism)
• Blotting, Western
• Brain (enzymology, pathology)
• Brain Ischemia (enzymology, pathology)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Cytochromes c (metabolism)
• Cytosol (drug effects, metabolism)
• Enzyme Activation (drug effects)
• Gene Expression (drug effects)
• Genes, bcl-2 (drug effects)
• Humans
• Infarction, Middle Cerebral Artery (pathology, prevention & control, psychology)
• Isoflurane (pharmacology)
• Male
• Mitochondria (drug effects, enzymology)
• Neuroprotective Agents
• Psychomotor Performance (drug effects)
• Rats
• Rats, Sprague-Dawley
• bcl-2-Associated X Protein (metabolism)