Linked Life Data

9056243

Source:http://linkedlifedata.com/resource/pubmed/id/9056243

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-4-16
pubmed:abstractText
Hepatic mitochondria contain inducible cytochromes P450 that cross-react with antibodies to P4501A1/2 and 2B1/2. In the present study, we present evidence for the occurrence of additional P450 forms in rat liver mitochondria that cross-react with antibodies to microsomal P4503A1/2 and 2E1. Protease protection and also immunoelectron microscopy studies were carried out to support the mitochondrial location of the immunoreactive P450s. The solubility of immunoreactive proteins in 0.1 M Na2CO3 suggests that the mitochondrial P450 forms tested are not membrane-integral proteins. The mitochondrial-associated P450 forms are capable of metabolizing resorufin derivatives, erythromycin, and p-nitrophenol in an adrenodoxin- and adrenodoxin reductase-supported system. Treatment of rats with phenobarbital (PB) resulted in the induction of mitochondrial pentoxyresorufin O-deethylase (PROD), benzoxyresorufin O-deethylase (BROD), and erythromycin N-demethylase (ERND) activities by 17-, 23-, and 2-fold, respectively. These activities were inhibited by 33 to 64% by antibodies to P4502B1/2 and P4503A1/2. The induction of the above monooxygenase activities correlated with the levels of mitochondrial proteins cross-reacting with antibodies to P4502B1/2 and P4503A1/2 in PB-treated livers. Similarly, administration of beta-naphthoflavone (BNF) resulted in a marked elevation of O-deethylation of ethoxy-, benzoxy-, and methoxyresorufins and a 2-fold increase in ERND activity. Immunoblot and immunoinhibition experiments using P4501A1/2, P4502B1/2, P4503A1/2, and P4502E1 antibodies revealed the presence of P450 forms closely related to the microsomal inducible forms. Results of immunoinhibition studies, using antibodies to adrenodoxin and reconstitution of enzyme activity with purified P450 forms, suggested a role for the mitochondrial P450 in the metabolism of xenobiotic substrates. The purified mitochondrial P450s also exhibited overlapping substrate specificities for resorufin derivatives and erythromycin.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0003-9861
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
339
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
136-50
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9056243-Adrenodoxin, pubmed-meshheading:9056243-Animals, pubmed-meshheading:9056243-Antibodies, Monoclonal, pubmed-meshheading:9056243-Cell Compartmentation, pubmed-meshheading:9056243-Cytochrome P-450 Enzyme System, pubmed-meshheading:9056243-Enzyme Induction, pubmed-meshheading:9056243-Enzyme Inhibitors, pubmed-meshheading:9056243-Immunohistochemistry, pubmed-meshheading:9056243-Intracellular Membranes, pubmed-meshheading:9056243-Isoenzymes, pubmed-meshheading:9056243-Male, pubmed-meshheading:9056243-Microsomes, Liver, pubmed-meshheading:9056243-Mitochondria, Liver, pubmed-meshheading:9056243-Molecular Weight, pubmed-meshheading:9056243-Rats, pubmed-meshheading:9056243-Rats, Sprague-Dawley, pubmed-meshheading:9056243-Substrate Specificity, pubmed-meshheading:9056243-Xenobiotics
pubmed:year
1997
pubmed:articleTitle
Localization of multiple forms of inducible cytochromes P450 in rat liver mitochondria: immunological characteristics and patterns of xenobiotic substrate metabolism.
pubmed:affiliation
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6047, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.