PMID- 10364221
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 25
DP  - 1999 Jun 18
TI  - Molecular cloning, enzymatic characterization, developmental expression, and
      cellular localization of a mouse cytochrome P450 highly expressed in kidney.
PG  - 17777-88
AB  - A cDNA encoding a new cytochrome P450 was isolated from a mouse liver library.
      Sequence analysis reveals that this 1,886-base pair cDNA encodes a 501-amino acid
      polypeptide that is 69-74% identical to CYP2J subfamily P450s and is designated
      CYP2J5. Recombinant CYP2J5 was co-expressed with NADPH-cytochrome P450
      oxidoreductase in Sf9 cells using a baculovirus system. Microsomal fractions of
      CYP2J5/NADPH-cytochrome P450 oxidoreductase-transfected cells metabolize
      arachidonic acid to 14,15-, 11,12-, and 8, 9-epoxyeicosatrienoic acids and 11-
      and 15-hydroxyeicosatetraenoic acids (catalytic turnover, 4.5 nmol of
      product/nmol of cytochrome P450/min at 37 degrees C); thus CYP2J5 is
      enzymologically distinct. Northern analysis reveals that CYP2J5 transcripts are
      most abundant in mouse kidney and present at lower levels in liver.
      Immunoblotting using a polyclonal antibody against a CYP2J5-specific peptide
      detects a protein with the same electrophoretic mobility as recombinant CYP2J5
      most abundantly in mouse kidney microsomes. CYP2J5 is regulated during
      development in a tissue-specific fashion. In the kidney, CYP2J5 is present before
      birth and reaches maximal levels at 2-4 weeks of age. In the liver, CYP2J5 is
      absent prenatally and during the early postnatal period, first appears at 1 week,
      and then remains relatively constant. Immunohistochemical staining of kidney
      sections with anti-human CYP2J2 IgG reveals that CYP2J protein(s) are present
      primarily in the proximal tubules and collecting ducts, sites where the
      epoxyeicosatrienoic acids are known to modulate fluid/electrolyte transport and
      mediate hormonal action. In situ hybridization confirms abundant CYP2J5 mRNA
      within tubules of the renal cortex and outer medulla. Epoxyeicosatrienoic acids
      are endogenous constituents of mouse kidney thus providing direct evidence for
      the in vivo metabolism of arachidonic acid by the mouse renal epoxygenase(s).
      Based on these data, we conclude that CYP2J5 is an enzymologically distinct,
      developmentally regulated, protein that is localized to specific nephron segments
      and contributes to the oxidation of endogenous renal arachidonic acid pools. In
      light of the well documented effects of epoxyeicosatrienoic acids in modulating
      renal tubular transport processes, we postulate that CYP2J5 products play
      important functional roles in the kidney.
FAU - Ma, J
AU  - Ma J
AD  - Laboratories of Pulmonary Pathobiology, NIEHS, National Institutes of Health,
      Research Triangle Park, North Carolina 27709, USA.
FAU - Qu, W
AU  - Qu W
FAU - Scarborough, P E
AU  - Scarborough PE
FAU - Tomer, K B
AU  - Tomer KB
FAU - Moomaw, C R
AU  - Moomaw CR
FAU - Maronpot, R
AU  - Maronpot R
FAU - Davis, L S
AU  - Davis LS
FAU - Breyer, M D
AU  - Breyer MD
FAU - Zeldin, D C
AU  - Zeldin DC
LA  - eng
SI  - GENBANK/U62294
GR  - P01-DK38226/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Eicosanoids)
RN  - 0 (Epoxy Compounds)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.14.1 (arachidonate epoxygenase)
RN  - EC 1.6.- (NADH, NADPH Oxidoreductases)
RN  - EC 1.6.2.4 (NADPH-Ferrihemoprotein Reductase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Arachidonic Acid/metabolism
MH  - Base Sequence
MH  - Cloning, Molecular
MH  - Cytochrome P-450 Enzyme System/chemistry/*genetics
MH  - Eicosanoids/analysis
MH  - Epoxy Compounds/metabolism
MH  - Gene Expression Regulation, Developmental
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Kidney/*enzymology
MH  - Kinetics
MH  - Mice
MH  - Molecular Sequence Data
MH  - NADH, NADPH Oxidoreductases/metabolism
MH  - NADPH-Ferrihemoprotein Reductase
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Recombinant Proteins
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1074/jbc.274.25.17777 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 18;274(25):17777-88. doi: 10.1074/jbc.274.25.17777.