Comparison of the Gene Expression Levels of Mevalonate Pyrophosphate Decarboxylase between Stroke-prone Spontaneously Hhypertensive and Wistar Kyoto Rats

Abstract

The relationship between protein and mRNA levels of mevalonate pyrophosphate decarboxylase (MPD) in rat tissues remains to be clarified. In this study, we examined the distribution of the mRNA in Wistar rat tissues by real-time PCR. When the relative expression of MPD in 1 mg of tissue was quantified using glyceraldehyde-3-phosphatedehydrogenase (GAPDH) as an internal control, the mRNA level was found to be markedly higher in the spleen and liver than in other organs. The correlation coefficient between protein and mRNA levels of MPD was 0.847, indicating that the protein level of MPD in Wistar rat is distributed in the tissues almost entirely dependent on the mRNA level of MPD. We previously reported that the protein levels of MPD in the liver and brain of spontaneously hypertensive rats, stroke-prone (SHRSP) are reduced. Thus, we compared mRNA levels of MPD in the liver and brain between Wistar Kyoto rats (WKY) and SHRSP. The levels in liver of SHRSP were significantly decreased, but not in brain, as compared with WKY. Also, mRNA levels of sterol regulatory element binding protein-2, which is transcription factor of cholesterol, in liver of SHRSP was similar to those of WKY. These findings indicate that the reduced protein level of MPD in the liver of SHRSP is caused by a decrease in mRNA level of MPD, and that in the brain of SHRSP is caused by increased degradation of the MPD protein.

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

“…34) We also reported that MPD mRNA levels in the liver were lower in SHRSP than in WKY. 35) These findings indicated that the reduced expression of MPD could be attributed to two causes. Low MPD mRNA levels in the livers of SHRSP may be caused by (1) a post-transcriptional effect (accelerated mRNA degradation or inhibited translation from mRNA to protein) or (2) reduction in the expression of heterogeneous nuclear RNA (hnRNA) at the transcriptional level.…”

Stroke‐prone spontaneously hypertensive rats have reduced hydroxysteroid 17‐β dehydrogenase 7 levels for low cholesterol biosynthesis

“…We have also previously shown that relative mRNA levels of IPI, SQS, LSS, sterol‐C5‐desaturase (SC5D), and 7‐dehydrocholesterol reductase (DHCR7) in the liver of SHRSP were the same as those in WKY . Further, the relative mRNA and protein levels of MPD and SQE were lower in the liver of SHRSP than in WKY . Anderson et al reported a correlation coefficiency of 0.48 between the abundance of mRNA and protein as determined by transcriptome and proteome analysis, suggesting that post‐transcriptional regulation of gene expression is a frequent phenomenon in higher organisms.…”

“…17 Further, the relative mRNA and protein levels of MPD and SQE were lower in the liver of SHRSP than in WKY. [18][19][20][21] Anderson et al 22 reported a correlation coefficiency of 0.48 between the abundance of mRNA and protein as determined by transcriptome and proteome analysis, suggesting that post-transcriptional regulation of gene expression is a frequent phenomenon in higher organisms. Because it cannot be concluded that decreased cholesterol synthesis is caused by the reduction of the abovementioned mRNA levels alone, an evaluation of protein levels and enzymatic activity is required.…”

Lower Squalene Epoxidase and Higher Scavenger Receptor Class B Type 1 Protein Levels Are Involved in Reduced Serum Cholesterol Levels in Stroke-Prone Spontaneously Hypertensive Rats

“…20) We also reported that MPD mRNA levels in the liver were lower in SHRSP than in WKY. 21) Furthermore, we found that reductions in MPD expression levels in the livers of SHRSP were suggested to be controlled by the upregulation of microRNA (miR)-214 and downregulation of transcriptional levels. 22) miR was shown to reduce protein levels by inhibiting its synthesis from mRNA or accelerating the degradation of mRNA.…”