Effects of peroxisome-proliferators on the TRP-NAD pathway.
The mechanism of the elevation of hepatic NAD level in the rats administered clofibrate and other peroxisome-proliferators were investigated. In the hepatocytes from the clofibrate-fed rats, NAD biosynthesis from Trp, but not from nicotinic acid, was specifically stimulated. The activities of peroxisomal marker enzymes, the peroxisome-proliferator activated receptors (PPAR)-dependent enzymes and key enzymes in the Trp-NAD pathway changed in parallel with the hepatic NAD increase; the activity of quinolinate phosphori-bosyltransferase (QPRT) was increased whereas that of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) was drastically reduced. The results strongly suggest that the hepatic NAD increase might be caused by transcription of genes coding the key enzymes of the Trp-NAD pathway via PPAR.
Shin
M
M
School of Pharmacy, Kobe-Gakuin University, Japan. shin@pharm.kobegakuin.ac.jp
Sano
K
K
Umezawa
C
C
D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism; D002478:Cells, Cultured; D002994:Clofibrate / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D009525:Niacin / Q000378:metabolism; D010084:Oxidation-Reduction; D010430:Pentosyltransferases / Q000378:metabolism; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D020675:Peroxisomes / Q000201:enzymology; D010640:Phenothiazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014364:Tryptophan / Q000378:metabolism*; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating)
D020025:Peroxisome Proliferators; D010640:Phenothiazines; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D009243:NAD; D009525:Niacin; D009249:NADP; D014364:Tryptophan; D010430:Pentosyltransferases; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating); D002262:Carboxy-Lyases; C024396:aminocarboxymuconate-semialdehyde decarboxylase; D002994:Clofibrate