Lithium

Goodwin, F. K.; Murphy, DennisL; Bunney, W. E.

doi:10.1016/s0140-6736(69)91446-9

Cited by 19 publications

(4 citation statements)

References 7 publications

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“…It (21). Relatively rapid spontaneous activation of cholesterol synthesis can occur in homogenates of rat liver (22), and it has been suggested that HMGCoA reductase activity may be subject to rapid regulation through a cyclic AMP-dependent protein kinase-phosphatase system (23 The concentrations of insulin required to enhance sterol synthesis and reductase activity are higher by approximately 3 orders of magnitude than those present in human serum but are similar to those used to demonstrate activity in various systems in vitro, including the stimulation of growth in fibroblasts (24). In our experiments with human fibroblasts, incorporation of thymidine into DNA was increased about 60% and of uridine into RNA 400% after incubation for 24 hr with insulin, while changes in protein synthesis were small and variable.…”

Section: Discussionmentioning

confidence: 99%

Effect of Insulin on Sterol and Fatty Acid Synthesis and Hydroxymethylglutaryl CoA Reductase Activity in Mammalian Cells Grown in Culture

Bhathena

Avigan

Schreiner

1974

Proc. Natl. Acad. Sci. U.S.A.

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The effects of insulin on the synthesis of sterols and fatty acids and on the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34), a rate-limiting enzyme for sterol synthesis, were studied in mammalian cells grown in culture. While in some established cell lines sterol synthesis was not affected significantly by the hormone, in the nonpermanent human and animal cells the synthesis of lipids, especially that of sterols, as well as the activity of the reductase were stimulated following an incubation with insulin in a medium containing serum albumin for a few hours or longer. These effects of insulin were also demonstrable in the presence of solvent-extracted serum, which itself increases sterol synthesis and reductase activity. In medium containing whole serum insulin was ineffective. Addition of glucose decreased sterol synthesis as well as reductase activity. The effects of insulin were prevented by cycloheximide and are probably due to an increased synthesis of 3-hydroxy-3-methylglutaryl CoA reductase or of a protein that regulates its activity.Insulin increases the activity of several biosynthetic processes in a number of mammalian tissues. Although little is known of its effects on the synthesis of sterols, increased cholesterol synthesis in rabbit aorta (1) and increased cholesterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA reductase; EC 1.1.1.34) activity in rat liver (2, 3) have been observed after administration of insulin in vivo.In cultured mammalian cells the rate of cholesterol synthesis is influenced by the lipid composition of the medium (4, 5) and it is probable that this is effected through alterations in HMGCoA reductase activity (6 Nonsaponifiable lipids, fatty acids, proteins, and DNA were isolated for radioassay as described earlier (4, 9). Incorporation is expressed as cpm/mg of total cell protein, which was determined by the method of Lowry (13).For assay of HMGCoA reductase activity, the washed cells from a single dish were scraped and suspended in 2 ml of 20 mM sodium phosphate buffer, pH 7.3, containing 2.5 mM EDTA, 3 mM MgCl2, and 10 mM 2-mercaptoethanol. After homogenization (Dounce homogenizer with "B" pestle) 0.2 ml of 1 M sodium phosphate buffer, pH 7.3, was added, and the homogenate was centrifuged, usually for 10 min at 600 X g. HMGCoA reductase was assayed in duplicate in a total volume of 1.5 ml containing 1.4 ml of 600 X g supernatant (100-300 Ag of protein), 3 mM NADP, 7 mM glucose-6-phosphate, 2.5 units of glucose-6-phosphate dehydrogenase (

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Section: Discussionmentioning

confidence: 99%

Effect of Insulin on Sterol and Fatty Acid Synthesis and Hydroxymethylglutaryl CoA Reductase Activity in Mammalian Cells Grown in Culture

Bhathena

Avigan

Schreiner

1974

Proc. Natl. Acad. Sci. U.S.A.

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“…Similarly, a 70-fold increase in HMG-CoA reductase activity which follows the weaning of rat pups was not blocked by cycloheximide (32). In addition, a rapid activation of microsomal reductase activity has been reported after incubation of rat or mouse liver homogenates at 370 (33,34). These rapid changes in HMG-CoA reductase activity are consistent with the interconversion of active-inactive forms of the enzyme as would be observed with the phosphorylation-dephosphorylation reaction mechanism.…”

Section: Hmg-coa Reductase Inactivation and Reactivationmentioning

confidence: 99%

3-Hydroxy-3-methylglutaryl coenzyme A reductase: regulation of enzymatic activity by phosphorylation and dephosphorylation.

Beg¹,

Stonik²,

Brewer³

1978

Proc. Natl. Acad. Sci. U.S.A.

128

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The activity of microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) [mev- Several different mechanism for the regulation of enzymes in metabolic pathways have been elucidated, including modulation by isosteric and allosteric effectors, regulation of enzyme synthesis and degradation, feedback control, and covalent modification (1-6). Covalent modification by phosphorylation-dephosphorylation is important in the regulation of glycogen synthetase, glycogen phosphorylase, phosphorylase b kinase, fructose 1,6-bisphosphatase, pyruvate dehydrogenase, hormone-sensitive lipase, and acetyl-coenzyme A carboxylase (1-3). Protein kinases and phosphoprotein phosphatases, which mediate the interconversion of phosphorylated and dephosphorylated forms, have been characterized in several systems (4, 5). The phosphorylated enzyme has been shown to be the active species (e.g., glycogen phosphorylase and phosphorylase b kinase) as well as the inactive form (e.g., glycogen synthetase and acetyl-CoA carboxylase) of the enzyme.Cholesterol biosynthesis in rat liver and in human skin fibroblast cells in culture is regulated by the enzymatic activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase)

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“…He was a rare scientist who focused on all levels of research—basic, translational, and clinical—and spanning neurochemical, genetic, molecular, clinical pharmacology, and behavioral approaches. His early work included investigations on the mechanisms of action of levodopa, lithium, and extensive research on monoamine oxidase (References plus over 130 papers). He authored a seminal paper on the linked‐polymorphic region in the serotonin transporter (SERT) gene promoter—a hallmark in the “birth” of the field of psychiatric genetics.…”

Section: Conflict Of Interestmentioning

confidence: 99%