RGD Reference Report - Contribution of CYP4A8 to the formation of 20-hydroxyeicosatetraenoic acid from arachidonic acid in rat kidney. - Rat Genome Database

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Contribution of CYP4A8 to the formation of 20-hydroxyeicosatetraenoic acid from arachidonic acid in rat kidney.

Authors: Yamaguchi, Y  Kirita, S  Hasegawa, H  Aoyama, J  Imaoka, S  Minamiyama, S  Funae, Y  Baba, T  Matsubara, T 
Citation: Yamaguchi Y, etal., Drug Metab Pharmacokinet. 2002;17(2):109-16.
RGD ID: 2303409
Pubmed: PMID:15618658   (View Abstract at PubMed)

20-Hydroxyeicosatetraenoic acid (20-HETE) has been shown to be an arachidonic acid metabolite of the cytochrome P450 (CYP) enzymes belonging to the CYP4A subfamily and is a predominant regulator of renal vascular tone and tubular ion reabsorption in rat kidney. CYP4A8 is one of the CYP4A enzymes expressed in rat kidney, but its contribution to 20-HETE formation has not been assessed. In order to clarify that the role of CYP4A8, we have developed bacterial expression systems for the expression of recombinant CYP4A8 (rCYP4A8). We also produced an antibody against rCYP4A8 which was used for immunoinhibition and immunohistochemical studies. In a reconstituted system, rCYP4A8 sufficiently catalyzed 20-HETE formation as well as prostaglandin A(1) omega-hydroxylation, a marker activity for CYP4A8. In addition, anti-rCYP4A8 sera significantly inhibited prostaglandin A(1) omega-hydroxylation and strongly inhibited arachidonic acid omega-hydroxylation in rat kidney microsomes. These observations suggested for the first time that CYP4A8 also contributed to 20-HETE formation in rat kidney. Furthermore, immunohistochemstry suggested that CYP4A8 is present in preglomerular arteries, where 20-HETE has been established to be a vasoconstrictor.




Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Cyp4a8Ratarachidonate metabolic process  IDA  RGD 
Cyp4a8Ratlauric acid metabolic process involved_inIDA PMID:15618658UniProt 

Cellular Component

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Cyp4a8Ratendoplasmic reticulum membrane located_inIDA PMID:15618658UniProt 

Molecular Function

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Cyp4a8Ratfatty acid omega-hydroxylase activity enablesIDA PMID:15618658UniProt 

RGD Manual Annotations


  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Cyp4a8Ratarachidonic acid metabolic pathway  IMP  RGD 

Genes (Rattus norvegicus)
Cyp4a8  (cytochrome P450, family 4, subfamily a, polypeptide 8)