Michihara Akihiro, Akasaki Kenji, Yamori Yukio, Tsuji Hiroshi
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima, Japan.
Biol Pharm Bull. 2003 Aug;26(8):1082-5. doi: 10.1248/bpb.26.1082.
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.
我们之前报道过，与未处理的大鼠相比，用含0.1%普伐他汀和5%消胆胺的饮食喂养大鼠，可显著提高肝脏粗提物中甲羟戊酸焦磷酸脱羧酶（MPD）的活性。在本研究中，我们检测了给予普伐他汀的小鼠组织中MPD蛋白水平的变化。当通过定量免疫印迹分析未处理小鼠组织中的MPD含量时，在所有组织中均检测到一条表观分子量为46 kDa的单一蛋白条带，肝脏和肾脏中MPD的特异性蛋白含量明显高于其他组织。当通过免疫印迹分析普伐他汀处理小鼠组织中的MPD含量时，与未处理小鼠相比，仅肝脏中的MPD显著增加（9倍）。接下来，当测量未处理和普伐他汀处理小鼠肝脏中的MPD活性时，与未处理小鼠相比，普伐他汀处理小鼠肝脏中的MPD活性以及蛋白水平均显著增加（11倍）。这些数据表明，普伐他汀对肝脏中MPD的显著诱导作用是普伐他汀组织特异性作用的原因。
