Change in the protein level of mevalonate pyrophosphate decarboxylase in tissues of mouse by pravastatin.
We previously reported that treatment of rats with a diet containing 0.1% pravastatin and 5% cholestyramine markedly increased mevalonate pyrophosphate decarboxylase (MPD) activity in liver crude extracts compared with nontreated rats. In this study, we examined the change in the protein level of MPD in the tissues of mice administered pravastatin. When MPD content in the tissues of nontreated mice was analyzed by quantitative immunoblotting, a single protein band with an apparent molecular weight of 46 kDa was detected in all tissues and the specific protein content of MPD in liver and kidney was markedly higher than that in other tissues. When MPD content in the tissues of pravastatin-treated mice was analyzed by immunoblotting, MPD was markedly increased (9-fold) only in the liver compared with nontreated mice. Next, when MPD activity was measured in the liver between nontreated and pravastatin-treated mice, MPD activity as well as protein levels were markedly increased (11-fold) in the liver of pravastatin-treated mice compared with nontreated mice. These data suggest that a marked induction of MPD in the liver by pravastatin is responsible for the tissue-specific effect of pravastatin.
Michihara
Akihiro
A
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima, Japan. mitihara@fupharm.fukuyama-u.ac.jp
Akasaki
Kenji
K
Yamori
Yukio
Y
Tsuji
Hiroshi
H
D000818:Animals; D002262:Carboxy-Lyases / Q000096:biosynthesis* / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D017035:Pravastatin / Q000008:administration & dosage / Q000494:pharmacology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
D011506:Proteins; D002262:Carboxy-Lyases; C022503:pyrophosphomevalonate decarboxylase; D017035:Pravastatin