Disease relevance of PIK3C2A

• Finally, intravenous wortmannin infusion induced sustained hypotension in rats, with inhibition of PI3K-C2alpha activity, GTP-loading of Rho and MYPT1 phosphorylation in the artery [1].
• CPK values in Parkinson's disease [2].
• Serial CPK determinations for evaluation of size and development of acute myocardial infarction [3].
• We conclude 1) new Q waves on ECG underestimate the incidence of myocardial damage after coronary artery surgery; 2) MB-CPK alone overestimates the incidence of infarction; and 3) a combination of the three techniques is the best means for detecting myocardial damage after coronary artery bypass graft surgery [4].
• Other selected variables--sex, CPK ratio and history of smoking, diabetes and hypertension--appear to be less clearly associated with ventricular arrhythmia [5].

Psychiatry related information on PIK3C2A

• The relationship between wrist-monitored motor activity and serum CPK activity in psychiatric in-patients [6].
• Physical stress will raise CPK, but the role of psychological stress has been unclear [7].
• Thus certain clinical and laboratory features such as anterior site of infarction, higher serum level of CPK and CPK-MB and severe alterations of left ventricular kinesis proved to be useful in identifying a subset of patients most likely to have LVT who may benefit from early anticoagulant therapy [8].
• In all patients there were elevated CPK levels, histological evidence of an acute myopathy, heavy alcohol intake prior to the development of symptoms, and improvement in hospital with the cessation of alcohol consumption [9].
• Furthermore, subjects with AMS on day 1 at BC were characterized by a greater decrease in the resting pain threshold and greater increase in resting LH, CPK and myoglobin compared with subjects without AMS (p < 0.05) [10].

High impact information on PIK3C2A

• Further, we show that endogenous PI3K-C2alpha is localized in coated pits and that exogenous expression affects clathrin-mediated endocytosis and sorting in the trans-Golgi network [11].
• Increased serum creatine kinase (CPK) activity has been reported to be present during acute exacerbations of psychosis in the majority of patients with the major "functional" psychoses [12].
• High mean serum CPK activity may be an indication of an increase in permeability of the muscle cell membrane, which in turn may be due to some defect in the neurotrophic regulation of muscle physiology or an independent expression of muscle abnormalities [12].
• The mean serum CPK level was also correlated with the terminal innervation ratio, an indication of alpha motor neuron dysfunction [12].
• The heart temperature was kept at 10 degrees to 15 degrees C. Patients were evaluated intraoperatively and postoperatively for (1) supraventricular tachycardia, (2) ECG changes, (3) lactate dehydrogenase and total CPK and isoenzyme (MB) studies, and (4) hemodynamic studies in the intensive care unit [13].

Chemical compound and disease context of PIK3C2A

• A radioimmunoassay was developed to measure serum levels of the B isoenzyme of creatine kinase(ATP: creatine N-phosphotransferase, EC 2.7.3.2) (CPK) in order to evaluate the time course and frequency of MB isoenzyme elevation in patients with acute myocardial infarction [14].
• To assess the incidence of perioperative myocardial infarction, 214 consecutive patients were evaluated 1-5 days after coronary bypass surgery, using Tc-99m pyrophosphate (TcPPi) myocardial imaging, serial electrocardiograms (ECG), and enzyme levels (SGOT, LDH, CPK) [15].
• Injection of 0.5 g/kg ethanol 1 h, but not 10 min, before ischemia reduced infarct size and CPK release [16].
• Hypoglycemia and elevated serum CPK, uric acid, and SGOT/SPGT were common [17].
• Chronic episodes of hypoxia/reoxygenation increased malondialdehyde (MDA), carbonyl derivates and creatine kinase (CPK) in plasma [18].

Biological context of PIK3C2A

• Further, a specific binding site was identified for clathrin on the N terminus of PI3K-C2alpha, whose occupancy resulted in lipid kinase activation [19].
• Biochemical analysis of recombinant PI3-K-C2 alpha demonstrates a restricted lipid substrate specificity [20].
• Left ventricular ejection fraction (EF) and percent akinesis (%A) were calculated from gated cardiac blood pool scans; myocardial infarct size was estimated from peak CPK values; and VPCs were detected by 24 hour ambulatory ECGs 2-4 weeks following hospitalization for acute MI [21].
• CP/CPK or aspirin alone reduced fibrinogen binding to 20% to 30%; however, this binding was sufficient to support full platelet aggregation [22].
• Here, we have identified a role for phosphatidylinositol 3-kinase C2alpha (PI3K-C2alpha) and its main catalytic product, PtdIns3P, in regulated exocytosis [23].

Anatomical context of PIK3C2A

• Differential centrifugation of COS-1 and U937 cells together with Western blot analysis demonstrated that PI3K-C2alpha is constitutively associated with phospholipid membranes [24].
• Together, these results reveal a molecular linkage between PI3K-C2alpha and the microtubule motor machinery, with implications for membrane trafficking in intact cells [25].
• The class II phosphoinositide 3-kinase PI3K-C2alpha is concentrated in the trans-Golgi network and present in clathrin-coated vesicles [24].
• PI3K-C2alpha was recently found to be localized to clathrin-coated membranes in the trans-Golgi network and at endocytic sites on the plasma membrane [19].
• These biochemical observations were supported by immunofluorescence analysis that revealed PI3K-C2alpha to have a punctate distribution and an enrichment of immunoreactivity within a perinuclear site consistent with its presence in the endoplasmic reticulum or Golgi apparatus [24].

Associations of PIK3C2A with chemical compounds

• Neither the phospholipid association nor the subcellular localization of PI3K-C2alpha was dependent upon either its COOH-terminal PX or C2 domains [24].
• Phosphoinositide 3-kinase C2alpha (PI3K-C2alpha) belongs to the class II phosphatidylinositol 3-kinases, which are defined by their in vitro usage of phosphatidylinositol and phosphatidylinositol 4-phosphate as substrates [26].
• Treatment of cells with brefeldin A disrupted the perinuclear staining pattern of both PI3K-C2alpha and the AP-1 complex demonstrating that the localization of both molecules at the TGN is dependent upon ADP-ribosylation factor GTPase activity [24].
• The catalytic activity of PI3-K-C2 alpha is refractory to concentrations of wortmannin and LY294002 which inhibit the PI3-K activity of other family members [20].
• These observations indicate that cAMP inhibits Ca(2+)-mediated activation of the MLCP-regulating signaling pathway comprising PI3K-C2alpha, Rho, and Rho kinase in a manner independent of Ca(2+) and point to the novel mechanism of the cAMP actions in the regulation of vascular smooth muscle contraction [27].

Regulatory relationships of PIK3C2A

• Down-regulation of PI3K-C2alpha expression by siRNA (small interfering RNA) inhibited contraction and phosphorylation of MYPT1 and MLC in VSM cells [1].
• Moreover, this MCP-1-induced increase in PI3K-C2alpha activity was insensitive to wortmannin but was inhibited by pertussis toxin pretreatment [28].

Other interactions of PIK3C2A

• Ligand addition also induced the appearance of a second, more slowly migrating band of PI3K-C2alpha and PI3K-C2beta immunoreactivity on sodium dodecyl sulfate-polyacrylamide gel electrophoresis [29].
• In this study, we demonstrate that PI3K-C2alpha and PI3K-C2beta represent two downstream targets of the activated epidermal growth factor (EGF) receptor in human carcinoma-derived A431 cells [29].
• Finally, an equivalent N-terminal fragment of PI3K-C2alpha that lacks similar proline-rich motifs was unable to affinity purify the activated EGF receptor from cell lysates [30].
• Centrifugation of rat brain homogenates and Western blotting revealed that in contrast to the class IA PI3K enzymes, PI3K-C2alpha could be co-purified with a population of clathrin-coated vesicles (CCVs) [24].
• Dual label immunofluorescence demonstrated that in this region, the distribution of PI3K-C2alpha closely paralleled that of gamma-adaptin, a component of the AP-1 adaptor that is present in the trans-Golgi and the trans-Golgi network (TGN) resident protein TGN-46 [24].

Analytical, diagnostic and therapeutic context of PIK3C2A

• Finally, immunoprecipitation experiments reveal an interaction between endogenous PI3K-C2alpha and dynactin subunits [25].
• In this report, we present evidence for an association between the presence of a transient elevation of serum CPK activity beyond the upper limit of normal during psychotic episodes and relatively high mean serum CPK levels during the rest of hospitalization [12].
• Physician decision was based upon history and once-daily ECG and total enzymes (CPK, SGOT, LDH) [31].
• LDH, CPK isoenzymes, and myocardial scintigraphy did not reveal myocardial damage [32].
• The diagnostic accuracy of creatine kinase (CPK), erythrocyte sedimentation rate, antinuclear antibody, and electromyography (EMG) were compared with the gold standard muscle biopsy [33].

References