| Differential expression of cytochrome P450 isoforms in the lungs of septic animals. | |
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MedLine Citation:
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PMID: 15190971 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Sepsis is characterized by an early, hyperdynamic phase and a late, hypodynamic phase. Although studies have shown that cytochrome P450 (CYP) plays an important role in the regulation of vascular reactivity, alterations of vascular CYP isoforms in sepsis remain unknown. Since CYP2C11 and CYP2J4 convert arachidonic acid to vasodilative epoxyeicosatrienoic acids, and CYP4A3 metabolizes arachidonic acid to both epoxyeicosatrienoic acids and vasoconstrictive 19,20-hydroxyeicosatetraenoic acid, the aim of this study was to examine the expression of these isoforms in sepsis and their association with hemodynamic changes. DESIGN: Prospective, controlled, and randomized animal study. SETTING: An institute research laboratory. SUBJECTS: Male adult Sprague-Dawley rats were subjected either to polymicrobial sepsis by cecal ligation and puncture or to sham operation followed by the administration of normal saline solution (i.e., fluid resuscitation). INTERVENTIONS: At 5 hrs (early sepsis) or 20 hrs (late sepsis) after cecal ligation and puncture, blood vessel-rich tissues (i.e., lungs) were harvested. The expression of CYP isoforms at both messenger RNA and protein levels was determined by reverse transcription polymerase chain reaction and Western blot analysis (CYP2C11), respectively. Hemodynamic variables were measured by radioactive microspheres. MAIN RESULTS: The results indicate that the gene expression of CYP2C11 and CYP2J4 was significantly down-regulated at 20 hrs after cecal ligation and puncture, whereas the expression of CYP4A3 was markedly up-regulated at 5 hrs. The protein concentrations of CYP2C11 also decreased significantly at 20 hrs after cecal ligation and puncture. Although total peripheral resistance markedly increased, mean arterial pressure did not change significantly at 20 hrs after the onset of sepsis. In contrast, cardiac output and pulmonary perfusion markedly decreased in late sepsis. CONCLUSIONS: Since the up-regulated CYP4A3 is associated with the early, hyperdynamic phase of sepsis and the down-regulated CYP2C11 and CYP2J4 are associated with the late, hypodynamic phase, vascular CYP isoforms that metabolize arachidonic acid may be involved in regulating the cardiovascular response during the progression of sepsis. |
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Authors:
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Xiaoxuan Cui; Rongqian Wu; Mian Zhou; H Hank Simms; Ping Wang |
Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Critical care medicine Volume: 32 ISSN: 0090-3493 ISO Abbreviation: Crit. Care Med. Publication Date: 2004 May |
Date Detail:
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Created Date: 2004-06-11 Completed Date: 2004-06-25 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0355501 Medline TA: Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 1186-91 Citation Subset: AIM; IM |
Affiliation:
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Division of Surgical Research, Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center, Manhasset, NY 11030, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arachidonic Acid / metabolism Aryl Hydrocarbon Hydroxylases / analysis, genetics, metabolism* Blood Pressure / physiology Cardiac Output / physiology Cecum / injuries Cytochrome P-450 Enzyme System / analysis, genetics, metabolism* Disease Models, Animal* Down-Regulation / physiology Hydroxyeicosatetraenoic Acids / metabolism Ligation Lung / chemistry, metabolism* Male Protein Isoforms Punctures Random Allocation Rats Rats, Sprague-Dawley Sepsis* / metabolism, physiopathology Steroid 16-alpha-Hydroxylase / analysis, genetics, metabolism* Time Factors Up-Regulation / physiology Vascular Resistance / physiology |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM053008/GM/NIGMS NIH HHS; R01 GM057468/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyp2j4 protein, rat; 0/Hydroxyeicosatetraenoic Acids; 0/Protein Isoforms; 506-32-1/Arachidonic Acid; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C11 protein, rat; EC 1.14.14.1/Steroid 16-alpha-Hydroxylase; EC 1.14.15.3/Cyp4a14 protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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