Lipid metabolism in spontaneously hypertensive rats (SHR)

Iritani, Nobuko; Fukuda, Eiko; Nara, Yasuo; Yamori, Yukio

doi:10.1016/0021-9150(77)90171-x

Cited by 79 publications

(48 citation statements)

References 20 publications

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“…In order to examine whether serum cholesterol levels in SHRSP reduce as described previously reported, 22) we compared not only total cholesterol, but also HDLand VLDL/LDL-cholesterol in serum between SHRSP and WKY. Total cholesterol (approximately 40%), HDL (approximately 40%), and VLDL/LDL (approximately 20%) cholesterol levels in serum were significantly lower in SHRSP than in WKY (Fig.…”

Section: Comparison Of Serum and Liver Cholesterol Levels Between Shrmentioning

confidence: 99%

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Involvement of microRNA214 and transcriptional regulation in reductions in mevalonate pyrophosphate decarboxylase mRNA levels in stroke-prone spontaneously hypertensive rat livers

Michihara

Ide

Mizutani

et al. 2015

Bioscience, Biotechnology, and Biochemistry

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Hypocholesterolemia has been epidemiologically identified as one of the causes of stroke (cerebral hemorrhage). We previously reported that lower protein levels of mevalonate pyrophosphate decarboxylase (MPD), which is responsible for reducing serum cholesterol levels in stroke-prone spontaneously hypertensive rats (SHRSP), in the liver were caused by a reduction in mRNA levels. However, the mechanism responsible for reducing MPD expression levels in the SHRSP liver remains unclear. Thus, we compared microRNA (miR)-214 combined with the 3′-untranslated region of MPD mRNA and heterogeneous nuclear RNA (hnRNA) between SHRSP and normotensive Wistar Kyoto rats (WKY). miR-214 levels in the liver were markedly higher in SHRSP than in WKY, whereas hnRNA levels were significantly lower. These results indicate that the upregulation of miR-214 and downregulation of MPD transcription in the liver both play a role in the development of hypocholesterolemia in SHRSP.

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Section: Comparison Of Serum and Liver Cholesterol Levels Between Shrmentioning

confidence: 99%

“…20,21) Serum cholesterol levels in these rats are lower than those in normotensive Wistar Kyoto rats (WKY). 22) Shiota et. al reported that the pathogenesis of stroke in SHRSP was inhibited by the feeding of high fat and cholesterol diets.…”

mentioning

confidence: 99%

Involvement of microRNA214 and transcriptional regulation in reductions in mevalonate pyrophosphate decarboxylase mRNA levels in stroke-prone spontaneously hypertensive rat livers

Michihara

Ide

Mizutani

et al. 2015

Bioscience, Biotechnology, and Biochemistry

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“…12) Iritani et al reported that the serum cholesterol level in SHRSP was low when compared with that in normotensive age-matched Wistar Kyoto rats (WKY). 13) We previously reported that the low serum cholesterol level in SHRSP as compared with WKY may be attributable to the reduced activity of MPD and not 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. 14) Moreover, we found that the decline in activity was caused by a reduction in the amount of enzyme in SHRSP.…”

Section: )mentioning

confidence: 99%

Purification and Characterization of Mouse Mevalonate Pyrophosphate Decarboxylase.

Michihara

Akasaki

Yamori

et al. 2002

Biological & Pharmaceutical Bulletin

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One of the first steps in the biosynthesis of cholesterol from acetic acid is catalyzed by mevalonate pyrophosphate decarboxylase (MPD). This decarboxylase catalyzes a bimolecular reaction between mevalonate 5-pyrophosphate (MVAPP) and ATP to form isopentenyl pyrophosphate, inorganic phosphate, adenosine-5Ј-diphosphate (ADP), and CO 2 .MPD has been purifed from various sources including yeast, 1,2) latex of Hevea brasiliensis, 3) pig liver, 4,5) rat liver, [6][7][8] and chicken liver. 9) Its properties in rat and chicken have been examined in detail. Toth and Huwyler reported cDNA sequences of MPD from human liver and yeast.10) The recombinant human enzyme is a homodimer of 43-kDa subunits with 400 amino acids. We recently established a procedure for the purification of MPD from the liver of rats fed a diet containing 5% cholestyramine and 0.1% pravastatin (CP diet) using chromatography and polyclonal antiserum raised against rat MPD. 8)Epidemiological studies have indicated a negative association between the serum cholesterol level and the incidence of cerebral hemorrhage in humans.11) Spontaneously hypertensive rat stroke-prone (SHRSP) is a widely used animal model for hypertension and stroke.12) Iritani et al. reported that the serum cholesterol level in SHRSP was low when compared with that in normotensive age-matched Wistar Kyoto rats (WKY). 13) We previously reported that the low serum cholesterol level in SHRSP as compared with WKY may be attributable to the reduced activity of MPD and not 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. 14) Moreover, we found that the decline in activity was caused by a reduction in the amount of enzyme in SHRSP.15) As described above, it is important to understand the mechanism of the decrease in MPD. We are also very interested in whether MPDknockout or MPD-reduced mice experience cerebral hemorrhage. However, information on MPD in normal mice is relatively scarce.In this paper, we describe a simple procedure for the purification of MPD from mouse liver, the properties of MPD, and a comparison of this MPD with counterparts from other animals. MATERIALS AND METHODSMaterials Pharmalyte 3-10 for isoelectric focusing and Western blotting detection kits were purchased from Amersham Pharmacia Biotech. Affigel 10 and 15 were obtained from Bio-Rad. RS-[ 3 H] mevalonolactone was purchased from Du Pont-New England Nuclear. Albumin from rat fraction V was purchased from Wako Chemicals. ddy Mice (8 weeks of age) were obtained from Shimizu Experimental Animals. All other chemicals were of reagent grade and purchased from commercial sources.Radioactive Assay The activities of the crude extract as well as the purified enzyme were measured according to the method of Sawamura et al.14) Unless otherwise indicated, the reaction mixture consisted of 100 mM Tris-HCl (pH 7.2), 5 mM ATP, 5 mM MgCl 2 , 10 mM NaF, Purification of MPD in RatsPurification of rat liver MPD was carried out as described by Michihara et al. 8)Preparation of an Affinity Column with Anti-rat MPD Antibody We...

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“…11,12) SHRSP has a lower serum cholesterol level than the normotensive Wistar Kyoto rat (WKY). 13) We previously indicated that the lower activity of MPD caused by the reduced amount of this enzyme was responsible for the reduced cholesterol biosynthesis in the liver of SHRSP. 14) However, the mechanism underlying the reduced amount of this enzyme remains unclear.…”

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confidence: 97%

Mevalonate Pyrophosphate Decarboxylase in Stroke-Prone Spontaneously Hypertensive Rat Is Reduced from the Age of Two Weeks.

Michihara

Sawamura

Yamori

et al. 2001

Biological & Pharmaceutical Bulletin

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Lipid metabolism in spontaneously hypertensive rats (SHR)

Cited by 79 publications

References 20 publications

Involvement of microRNA214 and transcriptional regulation in reductions in mevalonate pyrophosphate decarboxylase mRNA levels in stroke-prone spontaneously hypertensive rat livers

Involvement of microRNA214 and transcriptional regulation in reductions in mevalonate pyrophosphate decarboxylase mRNA levels in stroke-prone spontaneously hypertensive rat livers

Purification and Characterization of Mouse Mevalonate Pyrophosphate Decarboxylase.

Mevalonate Pyrophosphate Decarboxylase in Stroke-Prone Spontaneously Hypertensive Rat Is Reduced from the Age of Two Weeks.

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