| The inhaled anesthetic, isoflurane, enhances Ca2+-dependent survival signaling in cortical neurons and modulates MAP kinases, apoptosis proteins and transcription factors during hypoxia. | |
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MedLine Citation:
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PMID: 16861427 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We tested whether the protection of hypoxic neurons by the inhaled anesthetic isoflurane is related to the Ca2+-dependent phosphorylation of MAP kinases and anti-apoptotic co-factors. In cultures of mouse cortical neurons we measured changes in the phosphorylation of Ca2+-dependent and Ca2+-independent MAP kinases, transcription factors, and apoptosis regulators after hypoxia or hypoxia combined with isoflurane (1% in gas phase). In hypoxic neurons, isoflurane reduced cell death and TUNEL staining by >80%. Isoflurane released Ca2+ from intracellular stores, increasing [Ca2+]i in oxygenated neurons by approximately 20%. Neuroprotection was associated with a smaller increase in [Ca2+]i in hypoxic neurons and required IP3 receptors and phospholipase C. In hypoxic neurons, isoflurane increased the phosphorylation of the Ca2+-dependent MAP kinases Pyk2 and p42/44 (ERK). The Ca2+-independent MAP kinase p38 pathway showed increased phosphorylation with isoflurane but not with ionomycin, a Ca2+ ionophore. JNK was phosphorylated in hypoxic neurons in the presence of isoflurane, as was the transcription factor c-Jun; JNK inhibition with SP600125 prevented both phosphorylation of c-Jun and neuroprotection. Isoflurane decreased phosphorylation of the pro-apoptotic cofactors Bad and p90RSK and increased Akt phosphorylation. However, with the exception of c-Jun, transcription factors (Elk-1, GSK-3, Forkhead, p90RSK) decreased or remained unchanged. We conclude that isoflurane's protection of hypoxic cortical neurons involves signaling that includes changes in intracellular Ca2+ regulation, several MAP kinase pathways and modulation of apoptosis regulators. |
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Authors:
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Philip E Bickler; Christian S Fahlman |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Anesthesia and analgesia Volume: 103 ISSN: 1526-7598 ISO Abbreviation: Anesth. Analg. Publication Date: 2006 Aug |
Date Detail:
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Created Date: 2006-07-24 Completed Date: 2006-08-09 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 1310650 Medline TA: Anesth Analg Country: United States |
Other Details:
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Languages: eng Pagination: 419-29, table of contents Citation Subset: AIM; IM |
Affiliation:
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Severinghaus-Radiometer Research Laboratories, Department of Anesthesia and Perioperative Care, University of California at San Francisco, San Francisco, California 94143-0542, USA. bicklerp@anesthesia.ucsf.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anesthetics, Inhalation
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pharmacology* Animals Apoptosis / drug effects* Calcium / metabolism* Cell Hypoxia Cells, Cultured Cerebral Cortex / drug effects* Extracellular Signal-Regulated MAP Kinases / physiology In Situ Nick-End Labeling Isoflurane / pharmacology* MAP Kinase Signaling System / drug effects* Mice Neuroprotective Agents / pharmacology* Phosphorylation Proto-Oncogene Proteins c-akt / physiology Transcription Factors / metabolism* Type C Phospholipases / physiology p38 Mitogen-Activated Protein Kinases / physiology |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM 52212/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics, Inhalation; 0/Neuroprotective Agents; 0/Transcription Factors; 26675-46-7/Isoflurane; 7440-70-2/Calcium; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 3.1.4.-/Type C Phospholipases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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