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We previously reported that the lower activity of mevalonate pyrophosphate decarboxylase (MPD) was caused by the reduced amount of this enzyme in stroke-prone spontaneously hypertensive rat (SHRSP) by immunoblot analysis using 20,000 x g supernatant containing cytosol and microsomes. A recent study showed that at least three different subcellular compartments, including peroxisomes, are involved in cholesterol synthesis. In this study, we examined the subcellular distribution of 45- and 37-kDa MPD in the liver of SHRSP and compared normotensive Wistar Kyoto rat (WKY) and SHRSP. 45-kDa MPD was detected in the cytosol and peroxisomes of SHRSP, while 37-kDa MPD was detected in the cytosol of SHRSP, but not in the peroxisomes. The relative enrichment of 45-kDa MPD in peroxisomes was lower than that of LDH, suggesting the possibility that 45-kDa MPD of SHRSP did not exist in the peroxisomes. Also, 45-kDa MPD was decreased in the crude extract containing 1% Triton X-100, cytosol and peroxisomes of SHRSP, and 37-kDa MPD was decreased in the crude extract containing 1% Triton X-100 and cytosol of SHRSP, as compared with WKY. These data indicate that the cholesterol synthesis in the liver of SHRSP by the reduced amount of MPD is significantly reduced.

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Comparison of Subcellular Distribution of Mevalonate Pyrophosphate Decarboxylase between Stroke-Prone Spontaneously Hypertensive Rat and Wistar Kyoto Rat.