Pparo mediates induction of P450 4A10 in endotoxin-stimulated mice

T. H. Barclay, J. M. Peters, F. G. Gorzales, M. B. Sewer, E. T. Morgen

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Treatment of rats with bactrial real ni'Mit of tats wii h bacterial endotoxin result in 1 IK- down regulation of n iinmh.-r of cytorhrome P-loOs. and I lie induction of ('YIMA subfamily P l.> inHX l. 'In determine whrthcr the induction of CYP4A series l>y inflaininaii>rv aoiMit-, requires the peroxisome proliferatur activated receptor ( P PA R ), lw> <haract'-n/ed the reguhition of P-i) lalO in endotoxin-treated mice. Femalf mic- lveic injected with I nig/kg LPS. 400 nig/kg cloiihratc. or saline a a < nn t ml. Mi(e were sacrificed 24 hours after a single injection, and tissues were han-e-trd. In contrast to thr ral P450s 4A1. JA2 and 4A.'i. induction of P lof) la H) in I he wild type SV/129 strain of mouse was confined to the kidney. The expression of rytochronip P450 4aiO was reduced in wild-type moii.se liver with endoloxin treatment, in mice with a targeted disruption of l lie PPARa gene, emlotoxm treatment had no effect on P45U 4alO expression in either liver or kidnev. The.se data show that both the induction in kidney and the suppres sion in liver require PPARa. Other preliminary results suggest that PPAHa may be involved in suppression of other P-150s during endotoxin treatment l(s llt-ll. Supi.orted hy NTH grant (1M46S07.

Original languageEnglish (US)
Pages (from-to)A804
JournalFASEB Journal
Issue number9
StatePublished - 1997

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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