Michihara Akihiro, Akasaki Kenji, Yamori Yukio, Tsuji Hiroshi
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima, Japan.
Biol Pharm Bull. 2003 May;26(5):579-84. doi: 10.1248/bpb.26.579.
Mevalonate pyrophosphate decarboxylase (MPD) is considered to be a cytosolic protein. Recently, other groups reported that MPD is mostly located in the peroxisomes. In this study, we examined whether the expression of MPD in mice depends on the proliferation of peroxisomes, and whether MPD is predominantly located in the peroxisomes or the cytosol of mice. No increase in the protein level of MPD was observed in the crude extract of the livers of mice administered with peroxisome proliferative drugs. The result suggests that the expression of MPD is independent of the proliferation of peroxisomes, and may be maintained via a specific regulatory mechanism, different from the regulation of the expression of peroxisome proliferator-activated receptor alpha. When the subcellular distribution of MPD in mouse melanoma (B16F10) cells was examined by cell fractionation, MPD was detected in the cytosol of B16F10 cells, but not in the peroxisomes. In permeabilized B16F10 cells treated with digitonin, which lack cytosolic enzymes, 80% and 20% of MPD, 75% and 25% of lactate dehydrogenase, or 2% and 98% of catalase, existed in the medium and in the cell, respectively. From these results, it indicated that MPD was predominantly located in the cytosol and did not exist in the peroxisomes of B16F10 cells.
甲羟戊酸焦磷酸脱羧酶（MPD）被认为是一种胞质蛋白。最近，其他研究小组报道MPD主要位于过氧化物酶体中。在本研究中，我们研究了小鼠中MPD的表达是否依赖于过氧化物酶体的增殖，以及MPD主要位于小鼠的过氧化物酶体还是细胞质中。在用过氧化物酶体增殖药物处理的小鼠肝脏粗提物中，未观察到MPD蛋白水平的增加。结果表明，MPD的表达独立于过氧化物酶体的增殖，可能通过一种特定的调节机制维持，这与过氧化物酶体增殖物激活受体α的表达调节不同。当通过细胞分级分离法检测MPD在小鼠黑色素瘤（B16F10）细胞中的亚细胞分布时，在B16F10细胞的细胞质中检测到了MPD，但在过氧化物酶体中未检测到。在用缺乏胞质酶的洋地黄皂苷处理的透化B16F10细胞中，MPD分别有80%和20%、乳酸脱氢酶分别有75%和25%、过氧化氢酶分别有2%和98%存在于培养基和细胞中。从这些结果表明，MPD主要位于B16F10细胞的细胞质中，在过氧化物酶体中不存在。
