Peroxisome-proliferator regulates key enzymes of the tryptophan-NAD+ pathway.
Structually diverse peroxisome-proliferators (PPs) were investigated regarding their effects on NAD+ level and two key enzyme activities in the tryptophan (Trp)-NAD+ pathway in the liver of rats (Sprague-Dawley male) fed PP-containing diets freely for 2 weeks. All PPs, except for thyroxine, significantly increased hepatic NAD+ level in concert with hepatic hypertrophy. Activity of quinolinate phosphoribosyltransferase (QAPRTase), one of the key enzymes in the Trp-NAD+ pathway, was increased by the PPs which caused significant increase in the hepatic NAD+. On the other hand, alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSDase), another key enzyme in the Trp-NAD+ pathway, was drastically inhibited by all PPs except for linolenic acid, which was only slightly inhibitory. Most PPs investigated activated peroxisomal marker enzymes such as palmitoyl-CoA oxidase, catalase, and PPAR-alpha(peroxisome-proliferator activated receptor-alpha)-dependent enzymes, such as malic enzyme and l-3-glycerophosphate dehydrogenase. NAD+ was also increased in the rat hepatocytes cultured in the medium supplemented with PPs. These data suggested that regulation of the key enzymes in the Trp-NAD+ pathway was associated with PPAR-alpha directly or indirectly, and as a consequence the hepatic NAD+ was increased by PPs.
Shin
M
M
School of Pharmacy, Kobe Gakuin University, Nishi-ku, Kobe, 651-2180, Japan.
Ohnishi
M
M
Iguchi
S
S
Sano
K
K
Umezawa
C
C
D000818:Animals; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D004435:Eating / Q000187:drug effects; D006984:Hypertrophy / Q000139:chemically induced*; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D009243:NAD / Q000378:metabolism*; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D014364:Tryptophan / Q000378:metabolism*
D015415:Biomarkers; D020025:Peroxisome Proliferators; D009243:NAD; D014364:Tryptophan