Disease relevance of lovastatin

• We developed vector plasmids for the transformation of Halobacterium halobium, using the replicon region from the halobacterial phage H or from the plasmid pHH1 together with a DNA fragment conferring resistance to mevinolin [1].
• Mevinolin improved serum lipid levels and reduced albuminuria in 5/6 nephrectomy rats without causing significant alterations in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)[2]
• Abolition of mevinolin-induced growth inhibition in human fibroblasts following transformation by simian virus 40 [3].
• Proteinuria was reduced by antihypertensive therapy (P < .001) and lipid-lowering therapy (P < .05) (16-week values: 1.069 +/- 0.167 g/d in untreated rats, 0.663 +/- 0.164 g/d in the Lova group, 0.392 +/- 0.051 g/d in the AH group, and 0.176 +/- 0.035 g/d in the AH/Lova group).(ABSTRACT TRUNCATED AT 250 WORDS)[4]
• DNA histograms suggested that mevinolin arrests neuroblastoma cells in both the G1 and G2/M compartments of the cell cycle [5].

Psychiatry related information on lovastatin

• Vigorous physical activity and lovastatin (Mevacor) a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, have both been independently associated with elevated creatine kinase (CK) levels [6].

High impact information on lovastatin

• Smooth muscle cell lipid droplet accumulation occurred in the absence of serum lipoproteins and was not inhibited by mevinolin, a drug that blocks cholesterol synthesis [7].
• Suppression of murine neuroblastoma growth in vivo by mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase [8].
• Using an in vitro assay to monitor the ability of mouse serum to suppress sterol synthesis, we determined that mevinolin was inactivated or cleared from the circulation within 3-6 h after a single subcutaneous injection [8].
• We now report that mevinolin can inhibit neuroblastoma growth in vivo [8].
• Recent studies have shown that mevinolin, a competitive inhibitor of the reductase, inhibits cell proliferation and induces differentiation in cultured C1300 (Neuro-2A) murine neuroblastoma cells [8].

Chemical compound and disease context of lovastatin

• With the use of this technique and data from previously published series, the effects of the genetic absence of receptors, aging, and the treatment of hypercholesterolemia with mevinolin on LDL cholesterol kinetics were analyzed [9].
• H4-II-E-C3 hepatoma cells in culture respond to lipid-depleted media and to mevinolin with increased sterol synthesis from [14C]acetate and rise of 3-hydroxy-3-methylglutaryl coenzyme A reductase levels [10].
• Two agents which may be of value in treating hypercholesterolemia are mevinolin and neomycin [11].
• Effects of monoterpenes and mevinolin on murine colon tumor CT-26 in vitro and its hepatic "metastases" in vivo [12].

Biological context of lovastatin

• Two therapeutic measures that seem to increase the synthesis of LDL receptors are interruption of the enterohepatic circulation of bile acids with either bile-acid sequestrants or the ileal-exclusion operation, and competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase with mevinolin or compactin [13].
• A genetic determinant for resistance to the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor mevinolin was isolated by "shotgun cloning" into a derivative of the endogenous H. volcanii plasmid pHV2, to form pWL2, which transforms sensitive H. volcanii to mevinolin resistance at high frequency [14].
• To determine the mechanism for the LDL-lowering effect, we administered 131I-labeled LDL intravenously to six FH heterozygotes before and during treatment with mevinolin and calculated the apparent fractional catabolic rate (FCR) and synthetic rate for LDL [15].
• At a concentration of 1 microM mevinolin, the cardiac cells became quiescent and electrical stimulation induced action potentials of short duration without contraction [16].
• A frequent loss of all vectors (including pWL102) was observed in Hf. volcanii, where >90% of the mevinolin-resistant colonies obtained after transformation had lost the vector, presumably because of restriction endonuclease activity and concomitant recombination of the mevinolin resistance marker with the chromosome [1].

Anatomical context of lovastatin

• Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by mevinolin (lovastatin) specifically depletes endogenous isoprenoid pools and inhibits the conversion of prelamin A to lamin A. Prelamin A processing is also blocked by mevalonate starvation of Mev-1, a CHO cell line auxotrophic for mevalonate [17].
• Hydroxymethylglutaryl-coenzyme A reductase-containing hepatocytes are distributed periportally in normal and mevinolin-treated rat livers [18].
• Mevinolin inhibited mitogen-induced proliferation of normal and FH lymphocytes [19].
• We conclude that clinically effective doses of mevinolin do not affect corticosteroid production by the adrenal cortex during prolonged ACTH stimulation in patients with heterozygous familial hypercholesterolemia [20].
• In testis, an FPP synthetase-related RNA was detected that was larger than the liver FPP synthetase mRNA and was present at very high levels comparable with liver FPP synthetase RNA levels obtained from rats fed diets supplemented with cholestyramine and mevinolin [21].

Associations of lovastatin with other chemical compounds

• Normal cholesterol levels with lovastatin (mevinolin) therapy in a child with homozygous familial hypercholesterolemia following liver transplantation [22].
• Measurements of incorporation of (3H)acetate into neuroblastoma sterols and ubiquinones 24 h after implantation of osmotic pumps showed that mevinolin produced a marked inhibition of isoprenoid synthesis in the tumors in vivo [8].
• The hypothesis that short-term regulation of HMG-CoA reductase in tissues is quickly reflected by corresponding variations in plasma MVA was tested by using a specific inhibitor of HMG-CoA reductase, mevinolin, to block MVA synthesis [23].
• To determine the effectiveness of this combination and the mechanisms of lowering LDL levels, we measured turnover rates of LDL apoprotein (apo-LDL) before and during treatment with mevinolin and colestipol in eight patients with heterozygous familial hypercholesterolemia [13].
• To identify such signals, we arrested seedling development by specifically blocking the MVA pathway with mevinolin (MEV) or the MEP pathway with fosmidomycin (FSM) and searched for MEV-resistant Arabidopsis mutants that also could survive in the presence of FSM [24].
• The replication of dl1520 in ATC cells was enhanced by lovastatin treatment, and a significant increase of the expression of the early gene E1A 13 S and the late gene Penton was observed in lovastatin-treated cells [25].
• Lovastatin, by targeting mevalonate synthesis, is a potent inducer of the ISR through a novel and as yet unrecognized mechanism [26].

Gene context of lovastatin

• The statin, mevinolin, blocked chemotaxis through its effects on the MAPK pathway [27].
• Transcriptional derepression of the murine Cyp1a-1 gene by mevinolin [28].
• We show here that in the absence of TCDD, mevinolin markedly increases Cyp1a-1 transcription, CYP1A1 mRNA and protein levels and enzyme activity, and NMO1 mRNA concentrations [28].
• Approximately 9-fold increases in both HMG-CoA synthase mRNA mass and synthase mRNA activity were observed when control diets were supplemented with cholestyramine and mevinolin [29].
• Moreover, a serine substitution for Cys558 resulted in a single RK species whose migration on sodium dodecyl sulfate-polyacrylamide gels was identical to that of RK from cells treated with mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase and, thus, of isoprenoid biosynthesis [30].

Analytical, diagnostic and therapeutic context of lovastatin

• In a separate set of experiments, 5/6 nephrectomy rats were treated with the specific cholesterol synthesis inhibitor, mevinolin [2].
• Gel mobility shift assays revealed that Cyp1a-1 activation caused by mevinolin does not involve the ligand-dependent formation of a functional Ah receptor-dependent DNA-binding complex, but instead appears to be correlated with release of a putative repressor from its cognate DNA site [28].
• At a concentration of 25 microM, mevinolin completely inhibited the incorporation of [3H]acetate into ubiquinone, isolated from cell extracts by two-dimensional thin-layer chromatography [31].
• After treatment with 5 microM mevinolin, the cell cycle progression was completely blocked and two cell populations accumulated (80% in phase G0/G1 and 20% in G2/M) [32].
• Mevinolin treatment led to a partial synchronization, as shown by the increase in mitotic index [32].

References