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)

Protein phosphatase 2A1 was purified from rat skeletal muscle and used to produce antisera to the three subunits of the holoenzyme. Affinity purified antibodies specific for the subunits of the phosphatase enzyme were found to recognize the type 2A1 and 2A2 phosphatase from rat skeletal muscle, heart, liver, brain and erythrocytes and were used to investigate the effects of diabetes on the levels of this enzyme in liver and heart. Phosphorylase phosphatase assays coupled with immunoblot analysis of fractionated rat liver and heart cytosol from normal and diabetic animals show no apparent differences in the quantity or activity of these enzymes following the induction of alloxan diabetes. When considering these results and the normal physiological concentrations of known effectors of these enzymes, it is likely that protein phosphatase 2A1 and 2A2 are not responsible for the dephosphorylation of phosphorylase a under physiological conditions.
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PMID:Purification and the immunological characterization of rat protein phosphatase 2A: enzyme levels in diabetic liver and heart. 165 Apr 27

Alloxan diabetes induced in white rats by intraperitoneal injection of alloxan-monohydrate (15 mg/100 g body weight) was used to study changes in the glycogen phosphorylase a and b, phosphoprotein phosphatases and hexokinase activities under insulin deficiency conditions. Among the enzymes studied, an increase in muscle phosphorylase a activity as well as the a/b ratio have been obtained. In diabetic muscle phosphoprotein phosphatases and hexokinase activities were diminished. AMP increased the liver glycogen phosphorylase activity twice in diabetic rats whereas in normal animals the enzyme was less sensitive to this effector. The changes in liver hexokinase activity at diabetes were not connected and correlated with the altered phosphorylase and protein phosphatase activities. The logical chain of probable molecular events taking place in muscle glycogen metabolism under the conditions of insulin deficiency is offered.
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PMID:Changes in the activity of enzymes, participating in glycogen metabolism of alloxan diabetic rats. 255 79

In insulin-dependent diabetes mellitus there is a deficient post-prandial uptake of glucose and storage as glycogen in the liver. This impairment is due to an intrinsic hepatic defect that has been investigated with the use of isolated liver cells. Glycogen synthase catalyzes the rate-limiting step in the synthesis of glycogen. In response to an increased glucose concentration, this enzyme is activated in normal hepatocytes through dephosphorylation of seryl residues by a glycogen-bound "protein phosphatase G". Hepatocytes isolated from alloxan diabetes rats have lost the ability to activate glycogen synthase in response to an increased glucose concentration. The magnitude of the latter defect corresponds to the severity of the diabetes, as judged from the level of glycaemia. The defect is explained by an impaired function of protein phosphatase G. The latter enzyme consists of a catalytic subunit (37 kDa) associated with a large glycogen-binding subunit (161 kDa) and other regulatory polypeptides. It appears that in diabetes an essential regulatory subunit is deficient. Studies in animals with distinct types of spontaneous diabetes revealed that lack of insulin, rather than chronic hyperglycaemia, explains the deficient activity of protein phosphatase G.
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PMID:[Deficiency in hepatic uptake of glucose in chronic diabetes mellitus]. 256 13

Liver supernatant from normal and alloxan-diabetic rats was fractionated by DEAE-cellulose chromatography and the separated phosphoprotein phosphatase fractions were assayed with [32P]histone f2b, [32P]phosphorylase a and [32P]phosphorylase kinase as substrates. In diabetic rat liver, one of the phosphatase fractions found in the normal liver was significantly reduced. This fraction was identified as a mixture of the spontaneously active form and the ATP . Mg-dependent form of phosphoprotein phosphatase-1 (Fc) based on sensitivity to inhibitor-2, substrate specificity, and the fact that it could be activated 42-70% by glycogen synthase kinase-3 in the presence of ATP . Mg. Further analysis of this fraction showed that liver cytosol from diabetic rats contained 62-79% lower spontaneously active phosphatase-1 activity and 40-51% lower combined spontaneously active and ATP . Mg-dependent protein phosphatase-1 (Fc) activity. Insulin administration increased the spontaneously active and the ATP . Mg-dependent protein phosphatase-1 activities approximately 45% and 36%, respectively, in alloxan-diabetic rats. These data imply that the lower levels of spontaneously active phosphatase-1 activity in diabetic rat liver cannot be explained by presuming phosphatase-1 to have been present as Fc, the inactive form. Moreover, insulin restored the total activity of the spontaneously active and activatable forms of phosphatase-1 to those present in normal liver implying that both forms of phosphatase-1 activity are under hormonal control.
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PMID:Insulin-induced increases in the activity of the spontaneously active and ATP.Mg-dependent forms of phosphatase-1 in alloxan-diabetic rat liver. 298 4

It was shown previously in experiments on white rats with alloxan diabetes that trihydroxyoctadecadiene acids from Bryonia alba L. have a hypoglycemic action. The present paper is concerned with the effects of the above-indicated compounds on the activity of glycogen phosphorylase (a- and b-forms), phosphoprotein phosphatase and hexokinase in liver and muscle tissues of white rats with alloxan diabetes. One of the possible mechanisms of the hypoglycemic action of trihydroxyoctadecadiene acids is discussed.
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PMID:[Effect of trihydroxyoctadecadiene acids from Bryonia alba L. on the activity of glycogen metabolism enzymes in alloxan diabetes]. 632 80

Increased levels of protein O-linked N-acetylglucosamine (O-GlcNAc) have been shown to increase cell survival following stress. Therefore, the goal of this study was to determine whether in isolated neonatal rat ventricular myocytes (NRVMs) an increase in protein O-GlcNAcylation resulted in improved survival and viability following ischemia-reperfusion (I/R). NRVMs were exposed to 4 h of ischemia and 16 h of reperfusion, and cell viability, necrosis, apoptosis, and O-GlcNAc levels were assessed. Treatment of cells with glucosamine, hyperglycemia, or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)-amino-N-phenylcarbamate(PUGNAc), an inhibitor of O-GlcNAcase, significantly increased O-GlcNAc levels and improved cell viability, as well as reducing both necrosis and apoptosis compared with untreated cells following I/R. Alloxan, an inhibitor of O-GlcNAc transferase, markedly reduced O-GlcNAc levels and exacerbated I/R injury. The improved survival with hyperglycemia was attenuated by azaserine, which inhibits glucose metabolism via the hexosamine biosynthesis pathway. Reperfusion in the absence of glucose reduced O-GlcNAc levels on reperfusion compared with normal glucose conditions and decreased cell viability. O-GlcNAc levels significantly correlated with cell viability during reperfusion. The effects of glucosamine and PUGNAc on cellular viability were associated with reduced calcineurin activation as measured by translocation of nuclear factor of activated T cells, suggesting that increased O-GlcNAc levels may attenuate I/R induced increase in cytosolic Ca(2+). These data support the concept that activation of metabolic pathways leading to an increase in O-GlcNAc levels is an endogenous stress-activated response and that augmentation of this response improves cell survival. Thus strategies designed to activate these pathways may represent novel interventions for inducing cardioprotection.
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PMID:Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein-associated O-GlcNAc. 1689 50