Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholesterol esterification by acyl-CoA:cholesterol acyltransferase (ACAT; EC 2.3.1.26) has been studied in microsomes isolated from the mammary glands of rats in late pregnancy, in early and mid-lactation, and following premature weaning. The mammary glands were freeze-clamped and the microsomes prepared in the presence of phosphatase inhibitors to preserve the phosphorylation status of the enzyme. Optimal conditions were established for the assay of enzyme activity in the presence of endogenous cholesterol. Supplementation of the microsomes with exogenous cholesterol as a dispersion in Triton WR-1339 was shown to lead to an increase in enzyme activity. Incubation of microsomes with MgATP led to an increase in ACAT activity which could be reversed by treatment of the microsomes with a phosphoprotein phosphatase preparation from rat liver. The results suggested that ACAT activity in the mammary gland was activated by phosphorylation in a similar way to that observed for the hepatic enzyme. The mammary glands from pregnant animals contained a higher level of ACAT activity than did the glands of the lactating animals and this correlated with the higher cholesteryl ester content of the pregnant glands. The highest level of ACAT activity was found in the weaned animals but the cholesteryl ester content of the microsomes was lower than expected. The influence of progesterone levels and changes in feeding patterns during gestation were considered as factors in these variations in ACAT activity.
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PMID:Acyl-CoA: cholesterol acyltransferase activity in the rat mammary gland: variation during pregnancy and lactation. 205 98

Okadaic acid, calyculin A and cantharidin, potent and specific inhibitors of protein phosphatases 1 (PP1) and 2A (PP2A), stimulated both acyl-CoA:cholesterol acyltransferase (ACAT) activity and cholesterol ester formation in suspension cultures of isolated rat hepatocytes. The activation of microsomal ACAT was marked (up to 14-fold the basal values), fast in onset (within 5 min), persistent in duration (up to 45 min) and concentration-dependent. Concentrations of okadaic acid (OA) or calyculin A > or = 100 nM or of cantharidin > or = 1 microM were required to stimulate enzyme activity, which specifically points to a dominant contribution of PP1. No effects were seen with up to 1 microM nor-okadaone, an inactive OA analogue. Rises in [3H]oleate incorporation into cell cholesteryl esters closely paralleled those in ACAT activity, though were somewhat less accentuated. The increases in microsomal ACAT activity seen in OA-, calyculin A- or cantharidin-treated hepatocytes were not linked to changes in bulk microsomal unesterified cholesterol or in the de novo cholesterol synthesis. The findings firmly indicate a role for protein phosphatase activity, probably that of PP1, in controlling the cholesterol esterification rate and ACAT activity in intact rat hepatocytes, which is not secondary to an alteration of the steady-state distribution of cholesterol mass between cell membranes. However, as the OA-induced stimulation of ACAT was not abrogated by addition of purified PP1 or PP2A to microsomes, it is unlikely that the phosphatase inhibitors here used act directly on the phosphorylation degree of the ACAT enzyme.
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PMID:Protein phosphatase 1 and 2A inhibitors activate acyl-CoA:cholesterol acyltransferase and cholesterol ester formation in isolated rat hepatocytes. 943 37