Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study probes the regulation of cholesterol biosynthesis in the ocular lens by estimating the concentration and distribution of the messenger RNA for the rate-controlling enzyme for sterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). Because the lens is dependent on biosynthesis for cholesterol, HMGR activity is crucial for the life-long growth of this organ. Young rat lenses were serially divided into several fractions by dissolution in an SDS-containing buffer and each fraction was equated to a percent of the lens radius based upon its protein content. HMGR enzyme activity and cholesterol synthesis has been shown to disappear from the lens cortex over a narrow arc of radius due to loss of enzyme protein. Using a published competitive reverse transcriptase-polymerase chain reaction method for amplifying HMGR mRNA (Powell, E. E., and P. A. Kroon. 1992. J. Lipid Res. 33: 609-614), an average of about 46,000 copies of this mRNA was estimated per lens at all rat ages examined (5-day-old to adult). However, copies/microgram total RNA decreased with aging. The distribution of HMGR mRNA across 95-60% of the lens radius was essentially uniform at 2000-3000 copies/mm3 tissue. But the very superficial cortex contained 5- to 7-times this concentration and accounted for about 35% of the total copies/lens. We estimated that cells in this region each contained 1 to 2 copies of message, a value similar to the estimated copy number of HMGR message in human lymphocytes (Powell and Kroon, ibid). This suggests that the translational efficiency and stability of lens HMGR mRNA must be very high.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Spatial distribution of 3-hydroxy-3-methylglutaryl coenzyme A reductase messenger RNA in the ocular lens: relationship to cholesterologenesis. 753 8

1. We administered the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin at a daily dose of 1 mg kg(-1) body weight to cholesterol-fed (0.03%) heterozygous Watanabe heritable hyperlipidaemic rabbits, an animal model for heterozygous familial hypercholesterolaemia. 2. After 12 months of cholesterol treatment, immunohistochemistry with the monoclonal antibody 9D9 was used to detect hepatic low density lipoprotein (LDL) receptors, which were quantified by densitometry. In addition we determined LDL receptor mRNA by competitive reverse transcriptase polymerase chain reaction. The cholesterol precursor lathosterol and the plant sterol campesterol were analysed by gas-liquid chromatography. 3. The drug reduced total plasma cholesterol levels by 51% (P=0.04), when compared to the control group. Unexpectedly, hepatic LDL receptor density and mRNA showed no significant differences between the groups. Total plasma levels of lathosterol and campesterol also revealed no significant differences between the groups, if expressed relative to plasma cholesterol. 4. The findings suggest that mechanisms other than induced hepatic LDL receptors are responsible for the cholesterol-lowering effect of pravastatin in this animal model. We propose a reduced cholesterol absorption efficiency compatible with similar campesterol levels between both groups observed in our study.
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PMID:Effects of pravastatin on cholesterol metabolism of cholesterol-fed heterozygous WHHL rabbits. 964 43

Statin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is known to promote bone formation. However, it is not clear whether statin affects the differentiation of pulp cells. This study used a cell proliferation assay, cell cycle analysis, quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and in vivo transplantation to examine the effects of simvastatin on human dental pulp stem cells (DPSCs) in vitro and in vivo. Simvastatin at 1 mumol/L was able to significantly suppress the proliferation of DPSCs without inducing apoptosis. Quantitative RT-PCR revealed both osteocalcin and dentin sialophosphoprotein to be significantly up-regulated when DPSCs were cultured with simvastatin in comparison to bone morphogenetic protein-2 treatment. The in vivo transplantation data showed that simvastatin treatment promoted mineralized tissue formation. Taken together, these results suggest that statin might be an ideal active ingredient to accelerate the differentiation of DPSCs.
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PMID:Simvastatin induces the odontogenic differentiation of human dental pulp stem cells in vitro and in vivo. 1924 97

Recent evidence has indicated that type 2 diabetes mellitus is related to an increased risk of atrial arrhythmias, which might result from atrial structural and electrical remodeling. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins), known as lipid-lowering agents, have been shown to exert antiarrhythmic effects both in experimental models and in humans. In this study, we postulate that atrial structural and calcium channel remodeling may occur in streptozotocin-induced type 2 diabetic rats and can be alleviated by rosuvastatin (RSV) therapy. We randomly divided Wistar rats into control, untreated diabetic, RSV-treated control, and RSV-treated diabetic animals. After treatment with RSV for 4 weeks, rats were assessed by metabolic tests, histopathology, and transmission electron microscopy. The expression of Cav1.2, Cav3.1, and Cav3.2 in atrial tissues was detected by real-time reverse transcriptase polymerase chain reaction and Western blot, and inward calcium currents (l(Ca-L) and l(Ca-T)) were recorded in isolated atrial myocytes using patch-clamp techniques. Compared with controls, diabetic rats displayed severe metabolic disorders and a disorganized cellular ultrastructure. In diabetic rats, the expression of Cav1.2 mRNA and protein was significantly decreased, whereas that of Cav3.1 was significantly increased. Long-term RSV treatment partially relieved some pathological changes in diabetic rats. However, Cav3.2 mRNA and protein remained unchanged in control and diabetic groups and was unaffected by RSV. Diabetic atrial myocytes showed significantly reduced L-type but increased T-type, Ca (2+) currents, and this effect was significantly reversed by RSV. In conclusion, long-term RSV therapy can alleviate structural and calcium channel remodeling in the type 2 diabetic rat atrium.
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PMID:Rosuvastatin Alleviates Type 2 Diabetic Atrial Structural and Calcium Channel Remodeling. 2633 22