Differential effects of pyrazinamide and clofibrate on gene expression of rat hepatic alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase, a key enzyme of the tryptophan-NAD pathway.
Hepatic alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) [EC4.1.1.45] plays a key role in regulating NAD biosynthesis from tryptophan. The aim of this study was to evaluate the ACMSD mRNA expression after pyrazinamide or peroxisome proliferators ingestion. When rats were fed a control (pyrazinamide- and clofibrate-free) diet, 1% pyrazinamide- or 0.24% clofibrate-containing diets for 8 days, hepatic ACMSD activity and mRNA in rats consuming the clofibrate-containing diet was strongly suppressed, as compared with those fed the control and pyrazinamide diet. Pyrazinamide suppressed liver and kidney ACMSD activities, but did not affect ACMSD mRNA. Blood NAD was increased in the clofibrate and pyrazinamide groups. Shifting from the control diet to a clofibrate diet suppressed ACMSD mRNA strongly at day 1 and continued through day 4. However ACMSD activity decreased gradually. In rats fed with several kinds of peroxisome-proliferator-containing diets such as phthalate ester, bezafibrate, Wy-14,643, 2-(-4-chlorophenoxy) propionic acid, or dehydroisoandrosterone for 8 days, hepatic ACMSD mRNA was drastically decreased by all the peroxisome proliferators. These results suggest that the transcription level of hepatic ACMSD is modulated by peroxisome proliferators, and the fluctuation of the hepatic ACMSD mRNA expression was followed by that of the ACMSD activity. However, pyrazinamide does not affect the transcription level of hepatic ACMSD.
Egashira
Yukari
Y
Laboratory of Food and Nutrition, Graduate School of Science and Technology, Chiba University, Matsudo 271-8510, Japan.
Sato
Makiko
M
Sato
Mayuki
M
Sugawara
Ryoko
R
Tanabe
Atsushi
A
Shin
Mariko
M
Sanada
Hiroo
H
D000704:Analysis of Variance; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage*; D002262:Carboxy-Lyases / Q000235:genetics / Q000378:metabolism*; D002994:Clofibrate / Q000008:administration & dosage*; D018752:Diet, Fat-Restricted; D018753:Diet, Protein-Restricted; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D000960:Hypolipidemic Agents / Q000008:administration & dosage*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D009243:NAD / Q000235:genetics / Q000378:metabolism*; D020025:Peroxisome Proliferators / Q000008:administration & dosage / Q000378:metabolism; D011718:Pyrazinamide / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014364:Tryptophan / Q000235:genetics / Q000378:metabolism*; D015430:Weight Gain / Q000187:drug effects
D000995:Antitubercular Agents; D000960:Hypolipidemic Agents; D020025:Peroxisome Proliferators; D012333:RNA, Messenger; D009243:NAD; D011718:Pyrazinamide; D014364:Tryptophan; D002262:Carboxy-Lyases; C024396:aminocarboxymuconate-semialdehyde decarboxylase; D002994:Clofibrate