Distribution of cytochrome P-450 4A and 4F isoforms along the nephron in mice.

Academic Article

Abstract

  • The production of 20-hydroxyeicosatetraenoic acid (20-HETE) in the kidney is thought to be involved in the control of renal vascular tone and tubular sodium and chloride reabsorption. 20-HETE production in the kidney has been extensively studied in rats and humans and occurs primarily via the actions of P-450 enzymes of the CYP4A and -4F families. Recent advancements in molecular genetics of the mouse have made it possible to disrupt genes in a cell-type-specific fashion. These advances could help in the creation of models that could distinguish between the vascular and tubular actions of 20-HETE. However, isoforms of the CYP4A and -4F families that may be responsible for the production of 20-HETE in the vascular and tubular segments in the kidney of the mouse are presently unknown. The goal of this study was to identify the isoforms of the CYP4A and -4F families along the nephron by RT-PCR of RNA isolated from microdissected renal blood vessels and nephron segments from 16- to 24-wk-old male and female C57BL/6J mice. CYP4A and -4F isoforms were detected in every segment analyzed, with sex differences only observed in the proximal tubule and glomeruli. In the proximal tubular segments from male mice, the 4A10 and -12 isoforms were present, whereas the 4A10 and -14 isoforms were detected in segments from female mice. In glomeruli, sex differences in the expression pattern of CYP4F isoforms were also observed, with male mice expressing the 4F13, -14, and -15 isoforms, whereas female mice expressed the 4F13, -16, and -18 isoforms. These results demonstrate that isolated nephron and renal vessel segments express multiple isoforms of the CYP4A and -4F families; therefore, elimination of a single CYP4A or -4F isoform may not decrease 20-HETE production in all nephron segments or the renal vasculature of male and female mice. However, the importance of CYP4A vs. -4F isoforms to the production of 20-HETE in each of these renal tubular and vascular segments of the mouse remains to be determined.
  • Authors

    Published In

    Keywords

  • Animals, Arachidonic Acid, Cytochrome P-450 CYP4A, Cytochrome P-450 Enzyme System, Female, Gene Expression, Isomerism, Kidney Tubules, Collecting, Kidney Tubules, Proximal, Loop of Henle, Male, Mice, Mice, Inbred C57BL, Microcirculation, Microsomes, Mixed Function Oxygenases, Nephrons, Renal Circulation, Reverse Transcriptase Polymerase Chain Reaction, Sex Characteristics
  • Digital Object Identifier (doi)

    Author List

  • Stec DE; Flasch A; Roman RJ; White JA
  • Start Page

  • F95
  • End Page

  • 102
  • Volume

  • 284
  • Issue

  • 1