Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The change in intracellular Ca2+ concentration ([Ca2+]i) following platelet stimulation results from mobilization, influx and restoration of Ca2+. To determine whether inositol 1,4,5 trisphosphate (IP3) is involved in Ca2+ influx, the relationship between IP3 formation (IP3) and Ca2+ influx ( delta [Ca2+]i) was investigated in platelets stimulated wtih various agonists (thrombin, ADP, PAF, STA2, etc). The ratio of IP3 to delta [Ca2+]i varied among the agonists, although delta [Ca2+]i was increased, depending on the amount of agonist. Furthermore, in spite of the similar delta [Ca2+]i, IP3 was smaller at 20 degrees C compared with that at 37 degrees C in thrombin-stimulated platelets. These results indicate that Ca2+ influx in platelets might be regulated by receptor-operated Ca2+ channel rather than by an IP3 mediated mechanism. As for Ca2+ restoration, calpain was demonstrated to play a role through Ca(2+)-ATPase activation by limited proteolysis.
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PMID:[The regulatory mechanism of free Ca2+ concentration in activated platelets]. 131 11

The treatment of LDL with bee-venom phospholipase A2 resulted in the formation of lipid-protein particles (phl-LDL) with an increased content of lysophosphatidylcholine (LPC). At the same time, the composition of other lipids and the protein structure remained unaffected. phl-LDL, as well as LPC, abolished the hormone-induced [Ca2+] increase in platelets and platelet aggregation induced by PAF, AMP and thrombin, whereas LDL produced no effect on the hormone-stimulated increase in the intracellular [Ca2+]. The effect persisted in a Ca(2+)-free medium, indicating that phl-LDL and LPC did not abolish the mobilization of intracellular stores with the above-mentioned inducers. Neither LPC no phl-LDL affected the [Ca2+]i level in platelets and suppressed the platelet aggregation evoked by tapsigargine, a specific inhibitor of endoplasmic reticulum Ca(2+)-ATPase, or by phorbol myristate acetate. The inhibitory effect depended on the LPC concentration and the time of platelet incubation with phl-LDL or LPC. The half-maximum efficient LPC concentrations were identical for LPC and phl-LDL (2-4 microM). The inhibitory effect was dependent on the LPC structure: lysophosphatidylethanolamine and phosphatidylcholine displayed no inhibitory effect. The results suggest that when added to washed platelets, free LPC and phl-LDL inhibit only the receptor-dependent increase of [Ca2+]i.
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PMID:Effect of lysophosphatidylcholine on the structure and function of low density lipoproteins. 922 56

The present study is an extension of our previous work with the antineoplastic ether phospholipid ET-18-OCH3 (edelfosine), which was shown to affect the activity of the Ca(2+)-ATPase of rat brain synaptosomes and peritoneal leukocyte membranes. The effect of ET-18-OCH3 was compared with that of the 16-carbon chain analogue ET-16-OCH3 as well as with the structurally related 16- and 18-carbon PAFs (platelet-activating factors) and lyso-PAFs. In addition, the two alkylphosphocholines D-20166 and D-21266 (perifosine) were included in the investigation. The influence of all of the compounds followed the same pattern, i.e., the Ca(2+)-ATPase activity of the synaptosomes was increased over a relatively narrow concentration range (peak at 20-30 microM) and that of the leukocyte membranes was inhibited in a concentration-dependent manner by 10-50 microM concentrations of the drugs. Ether phospholipids with an 18-carbon chain at C-1 were more potent than those with a 16-carbon chain. All of the compounds increased the activity of the synaptosomal ATPase to the same extend (ca. 50%). With the exception of lyso-PAF, all inhibited the enzyme activity of leukocyte membranes by 60-70%, whereas lyso-PAF was less effective (ca. 50% inhibition). The concentration range of activity for PAF and lyso-PAF indicates that their effect on the enzyme activity was caused by receptor-independent mechanisms. The ether phospholipids and alkylphosphocholines are suggested to act by accumulating in the membranes and thereby altering the character of the lipid environment of the enzyme rather than by a direct interaction with the Ca(2+)-ATPase.
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PMID:Similar effects of ether phospholipids, PAF and lyso-PAF on the Ca(2+)-ATPase activity of rat brain synaptosomes and leukocyte membranes. 1146 Mar 12

Treatment of LDL with phospholipase A from bee venom resulted in formation of lipid-protein particles (pl2 LDL) with increased content of lysophosphatidylcholine (LPC). At the same time, composition of other lipids and protein structure were unaffected. Both pl-LDL and LPC abolished PAF-, ADP- and thrombin-induced Ca2+ elevation in platelets and platelet aggregation, while LDL had no effect on hormone-stimulated increase in the intracellular Ca2+ content ({Ca2+}i). The effect persisted in Ca2+-free medium, indicating that pl-LDL and LPC also abolish Ca2+ mobilisation from intracellular stores. Neither LPC nor pl-LDL changed platelet Ca2+ levels and inhibited platelet aggregation induced by thapsigargin, a specific inhibitor of the endoplasmic reticulum Ca2+ ATPase. The inhibitory effect depended on LPC concentration, incubation time and the structure of LPC: lysophosphatidylethanolamine and phosphatidylcholine produced no inhibitory effect. The half-maximum-effective concentrations were the same for LPC and pl-LDL (2-4 microM). The results obtained indicate that LPC and pl-LDL inhibit the receptor-dependent increase in Ca2+. It can be suggested that the effect of LPC is mediated by redistribution of the plasma membrane integral proteins, which leads to disintegration of the intracellular signalling systems.
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PMID:Inhibitory effect of lysophosphatidylcholine and phospholipase A2-treated low density lipoproteins on receptor-dependent regulation of {Ca2+}i in platelets. 1679 32

Change in gene expression associated with pancreatic cancer could be attributed to the variation in histone posttranslational modifications leading to subsequent remodeling of the chromatin template during transcription. However, the interconnected network of molecules involved in regulating such processes remains elusive. hPaf1/PD2, a subunit of the human PAF-complex, involved in the regulation of transcriptional elongation has oncogenic potential. Our study explores the possibility that regulation of histone methylation by hPaf1 can contribute towards alteration in gene expression by nucleosomal rearrangement. Here, we show that knockdown of hPaf1/PD2 leads to decreased di- and tri-methylation at histone H3 lysine 4 residues in pancreatic cancer cells. Interestingly, hPaf1/PD2 colocalizes with MLL1 (Mixed Lineage Leukemia 1), a histone methyltransferase that methylates H3K4 residues. Also, a reduction in hPaf1 level resulted in reduced MLL1 expression and a corresponding decrease in the level of CHD1 (Chromohelicase DNA-binding protein 1), an ATPase dependent chromatin remodeling enzyme that specifically binds to H3K4 di and trimethyl marks. hPaf1/PD2 was also found to interact and colocalize with CHD1 in both cytoplasmic and nuclear extracts of pancreatic cancer cells. Further, reduced level of CHD1 localization in the nucleus in hPaf1/PD2 Knockdown cells could be rescued by ectopic expression of hPaf1/PD2. Micrococcal nuclease digestion showed an altered chromatin structure in hPaf1/PD2-KD cells. Overall, our results suggest that hPaf1/PD2 in association with MLL1 regulates methylation of H3K4 residues, as well as interacts and regulates nuclear shuttling of chromatin remodeling protein CHD1, facilitating its function in pancreatic cancer cells.
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PMID:Human RNA polymerase II-association factor 1 (hPaf1/PD2) regulates histone methylation and chromatin remodeling in pancreatic cancer. 2204 13