Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1832588 (PSS)
 2,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A specific radioimmunoassay was developed to the predicted nine amino acid C-terminal flanking peptide of cholecystokinin (peptide serine serine, PSS). In aqueous extracts of rat brain, PSS was undetectable unless the extracts were first treated with arylsulphatase, which also resulted in desulphation of cholecystokinin. The reverse-phase HPLC analysis of partially desulphated extracts showed the presence of two peaks intermediate to the naturally occurring and the completely desulphated forms. It is therefore proposed that the CCK-flanking peptide PSS has both tyrosine residues sulphated.
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PMID:Is the C-terminal flanking peptide of rat cholecystokinin double sulphated? 394 32

Amine-containing phospholipid synthesis in Saccharomyces cerevisiae starts with the conversion of CDP-diacylglycerol (CDP-DAG) and serine to phosphatidylserine (PS), whereas phosphatidylinositol (PI) is formed from CDP-DAG and inositol (derived from inositol 1-phosphate). In this study the regulation of PS synthase (encoded by CHO1/PSS), PI synthase (encoded by PIS1), and inositol 1-phosphate synthase (encoded by INO1) activities by the in vivo level of CDP-DAG synthase activity (encoded by CDS1) is described. Reduction in the level of CDP-DAG synthase activity from 10-fold over wild type levels to 10% of wild type levels results in a 7-fold increase in PS synthase activity, which follows a similar change in the CHO1/PSS mRNA level. INO1 mRNA also increases but only after CDP-DAG synthase activity falls below the wild type level. PI synthase activity follows the decrease of the CDP-DAG synthase activity, but there is no parallel change in the level of PIS1 mRNA. These changes in CHO1/PSS and INO1 mRNA levels are mediated by a mechanism not dependent on changes in the expression of the INO2-OPI1 regulatory genes. CDS1 expression is repressed in concert with INO2 expression in response to inositol.
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PMID:Regulation of phospholipid biosynthetic enzymes by the level of CDP-diacylglycerol synthase activity. 911 Oct 22

Phosphatidylserine (PtdSer) in mammalian cells is synthesized through an exchange of free L-serine for the base moiety of pre-existing phospholipids. Studies on PtdSer biosynthesis in Chinese hamster ovary (CHO) cells have suggested that the serine base-exchange is catalyzed by at least two different enzymes; one, named PtdSer synthase I (PSS I), uses phosphatidylcholine (PtdCho) and possibly phosphatidylethanolamine (PtdEtn) as phosphatidyl donors for the serine base-exchange, and the other, named PtdSer synthase II (PSS II), uses PtdEtn but not PtdCho as a phosphatidyl donor. Recently, cDNAs of the PSS I and II have been isolated from CHO-K1 cells. This review will briefly describe the current understanding of PtdSer synthases of mammalian cells, mainly CHO cells.
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PMID:Phosphatidylserine synthase I and II of mammalian cells. 937 Mar 27

Whereas mammalian cells produce PS by a base exchange reaction from preexisting phospholipids, yeast cells synthesize PS from CDP-diacylglycerol and serine by the PS synthase reaction. Yeast PS synthase was purified to homogeneity and shown to have a molecular mass of 23 kDa. The activity is dependent on either Mg2+ or Mn2+ and Triton X-100. The enzyme specifically transfers the phosphatidyl group from CDP-diacylglycerol or dCDP-diacylglycerol to L-serine, but not to threonine, cysteine and ethanolamine. The PSS/CHO1 gene encoding the enzyme was cloned by the complementation of the choline auxotrophic pss/cho1 mutant. The deduced protein comprises 279 amino acids with a calculated molecular mass of 30,804. The primary translate undergoes proteolytic processing to the enzymatically more active 23-kDa enzyme. The deduced amino acid sequence contains several putative membrane-spanning regions and resembles that of the Bacillus subtilis enzyme, but not those of the E. coli and Haemophilus influenzae enzymes. The sequence also contains the local, conserved region found in enzymes catalyzing the transfer of the phosphoalcohol moiety from CDP-alcohol, such as PI synthase, cholinephosphotransferase and phosphatidylglycerolphosphate synthase. The activity of PS synthase is maximal in the exponential phase, but decreases when cells enter the stationary phase. The enzyme is phosphorylated at a single serine residue by cyclic AMP-dependent protein kinase with a 60-70% decrease in enzymatic activity, but the primary translation product is not phosphorylated. PS synthase is inhibited by CTP, probably due to the chelation of the divalent cations, Mg2+ and Mn2+, and also by sphingoid bases, such as sphinganine and phytosphingosine. Phosphatidate, phosphatidylcholine and phosphatidylinositol are stimulatory, whereas cardiolipin and diacylglycerol are inhibitory. The expression of yeast PS synthase is transcriptionally repressed by myo-inositol and choline in a coordinate manner with other phospholipid-synthesizing enzymes. The upstream regulatory region of the PSS/CHO1 gene responsible for the myo-inositol-choline regulation was identified. An octameric sequence, CATRTGAA (R = A or G), plays an important role in the conferral of the myo-inositol-choline transcriptional regulation.
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PMID:Phosphatidylserine synthase from yeast. 937 Mar 37

We report the subcellular localization of enzymes involved in phosphatidylserine biosynthesis in mammalian cells. Several lines of evidence suggest that phosphatidylserine synthase-1 (PSS1) is highly enriched in mitochondria-associated membranes (MAM) and is largely excluded from the bulk of the endoplasmic reticulum (ER). Taking advantage of the substrate specificity of PSS1, we showed that (i) MAM contain choline exchange activity, whereas this activity is very low in the bulk of the ER, (ii) serine exchange activity is inhibited by choline to a much greater extent in MAM than in ER, and (iii) MAM use phosphatidylcholine and phosphatidylethanolamine as substrates for phosphatidylserine biosynthesis, whereas the ER utilizes only phosphatidylethanolamine. According to immunoblotting of proteins from both CHO-K1 cells and murine liver, PSS1 is localized to MAM, and in hepatoma cells stably expressing PSS1 this protein is highly enriched in MAM. Since the ER contains serine and ethanolamine exchange activities, we had predicted that PSS2 would account for the serine exchange activity in the ER. Unexpectedly, using immunoblotting experiments, we found that (i) PSS2 of CHO-K1 cells is present only in MAM and (ii) PSS2 is restricted to MAM of McArdle cells expressing recombinant PSS2. These data leave open the question of which enzyme imparts PSS activity to the ER and suggest that a third isoform of PSS might be located in the ER.
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PMID:Phosphatidylserine synthase-1 and -2 are localized to mitochondria-associated membranes. 1093 71

Externalization of PtdSer (phosphatidylserine) is an important event in signalling removal of apoptotic cells. In contrast with previous work [Yu, Byers, Ridgway, McMaster and Cook (2000) Biochim. Biophys. Acta 1487, 296-308] with U937 cells showing that specific stimulation of PtdSer biosynthesis during apoptosis was caspase dependent, PtdSer biosynthesis in CHO (Chinese-hamster ovary)-K1 increased 2.5-fold during UV-induced apoptosis but was not reversed by a caspase inhibitor, Z-VAD-FMK (benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone). Also, in CHO-K1 cells, stimulation of synthesis was less specific for PtdSer as similar levels of stimulation were observed for sphingomyelin biosynthesis. Involvement of PtdSer synthase isoforms was tested in CHO-K1 cells overexpressing PSS I (PtdSer synthase I) and PSS II. Both types of transformed cells showed resistance to UV-induced apoptosis based on the decreased levels of caspase 3 activation and morphology changes; externalization of PtdSer was reduced with UV treatment even though expression of endogenous scramblase increased slightly. Serine-labelling experiments showed that PSS I- or PSS II-expressing cells had higher basal levels of PtdSer biosynthesis compared with vector control cells. When cells were exposed to UV light to induce apoptosis, PtdSer biosynthesis was further stimulated 1.5- and 2-fold in PSS I- and PSS II-expressing cells respectively compared with UV-treated vector cells. Caspase activation was not required, as Z-VAD-FMK did not change PtdSer synthesis. Although enhanced PtdSer synthesis was supposed to facilitate apoptosis, cells overexpressing PSS I and II were actually resistant to UV-induced apoptosis. Whereas enhanced PtdSer synthesis was associated with apoptosis, potential anti-apoptotic effects were observed when excess activity of these synthetic enzymes was present. This suggests a tightly regulated role for PtdSer synthesis and/or an important dependence on compartmentation of PSS enzymes in association with scramblase facilitated enrichment of this phospholipid at the cell surface.
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PMID:Resistance to UV-induced apoptosis in Chinese-hamster ovary cells overexpressing phosphatidylserine synthases. 1509 92

PtdSer (phosphatidylserine) synthesis in mammalian cells occurs through the exchange of L-serine with the base moieties of phosphatidylcholine and phosphatidylethanolamine, which is catalysed by PSS (PtdSer synthase) 1 and 2 respectively. PtdSer synthesis in intact cells and an isolated membrane fraction was inhibited by exogenous PtdSer, indicating that feedback control is involved in the regulation of PtdSer biosynthesis. PSS 1 and 2 are similar in amino acid sequence, with an identity of 32%; however, due to a lack of homology with other known enzymes, their amino acid sequences do not provide information on their catalytic and regulatory mechanisms. In the present study, to identify amino acid residues crucial for the activity and/or regulation of PSS 1, we systematically introduced mutations into a Chinese hamster PSS 1 cDNA clone; namely, each of the 66 polar amino acid residues common to PSS 2 was replaced with an alanine residue. On analysis of Chinese hamster ovary cells transfected with each of the alanine mutant clones, we identified eight amino acid residues (His-172, Glu-197, Glu-200, Asn-209, Glu-212, Asp-216, Asp-221 and Asn-226) as those crucial for the enzyme reaction or the maintenance of the correct structure required for serine base-exchange activity. Among these residues, Asn-209 was suggested to be involved in the recognition and/or binding of free L-serine. We also identified six amino acid residues (Arg-95, His-97, Cys-189, Arg-262, Gln-266 and Arg-336) as those important for regulation of PSS 1. In addition, we found that the alanine mutations at Tyr-111, Asp-166, Arg-184, Arg-323, and Glu-364 affected the production and/or stability of PSS 1 in Chinese hamster ovary cells.
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PMID:Functional analysis of Chinese hamster phosphatidylserine synthase 1 through systematic alanine mutagenesis. 1513 88

Apoptosis, or programmed cell death, plays an important role in many physiological and diseased conditions. Induction of apoptosis in cancer cells has been monitored during the cells' progression to apoptosis by anti-cancer drugs and inhibitors of the cell surface glycolipids, gangliosides and SA-Le(x) biosyntheses [Basu, S (1991) Glycobiology, 1, 469-475; and ibid, 427-435] in animal tissues and human carcinoma cells, respectively. Induction of apoptosis in cancer cells by cell surface glycolipids in the human breast cancer (SKBR3) cells is the aim in this study. We have employed the disialosyl gangliosides (GD3 and GD1b) to initiate apoptosis in SKBR3 cells grown in culture in the presence of (14)C-L-Serine. At lower concentrations (0-20 microM) of exogenously added non-radioactive GD3, GD1b, or bovine ganglioside mixture (GM1:GD1a:GD1b:GT1a 2:4:4:2), the incorporation of radioactivity in both (14)C-sphingolipid and (14)C-ceramide was higher. However, at higher concentrations (20-100 microM), wherein apoptosis occurred in high frequency, the (14)C-incorporation decreased in both GSLs and ceramide. Apoptosis induction was monitored by the concomitant appearance of caspase-3 activation and the binding of a fluorescent dye PSS-380 to the outer leaflet of phosphatidyl-serine. These results indicated that, in addition to many unknown cell surface glycoconjugates GD3 or GD1b (disialosyl ganglioside) could play an important role in the regulation of breast carcinoma cell death.
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PMID:Apoptosis of human breast carcinoma cells in the presence of disialosyl gangliosides: II. Treatment of SKBR3 cells with GD3 and GD1b gangliosides. 1522 96

Breast cancer is the most common type of cancer, predominantly among women over 20, whereas colo-rectal cancer occurs in both men and women over the age of 50. Chemotherapy of both cancers affect rapidly growing normal as well as cancer cells. Cancer cells are non-apoptotic. Seven anti-cancer agents (cis -platin, Tamoxifen, Melphalan, Betulinic acid, D-PDMP, L-PPMP, and GD3) have been tested with human breast (SKBR3) and colon (Colo-205) carcinoma cells for their apoptotic effect and found to be positive by several assay systems. Colo-205 cells were obtained from ATCC, and the SKBR3 cells were a gift from the Cleveland Clinic. All of these six agents killed those two cell lines in a dose-dependent manner. In the early apoptotic stage (6 h), these cells showed only a flopping of phosphatidylserine on the outer lamella of the plasma membranes as evidenced by the binding of a novel fluorescent dye PSS-380. After 24 h of the treatment, those apoptotic cells showed damage of the plasma as well as the nuclear membrane as evidenced by binding of propidium iodide to the nuclear DNA. DNA laddering assay viewed further breakdown of DNA by 1% agarose gel electrophoresis analysis. It is concluded that during apoptosis the signaling by Mitochondrial Signaling Pathway (MSP) is stimulated by some of these agents. Caspase 3 was activated with the concomitant appearance of its p17 polypeptide as viewed by Westernblot analyses. Incorporation of radioactivity from [U-(14)C]-L-serine in total sphingolipid mixture was observed between 2 and 4 micromolar concentrations of most of the agents except ci s-platin. However, apoptosis in carcinoma cells in the presence of cis -platin is induced by a caspase 3 activation pathway without any increase in synthesis of ceramide.
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PMID:Apoptosis of human carcinoma cells in the presence of potential anti-cancer drugs: III. Treatment of Colo-205 and SKBR3 cells with: cis -platin, Tamoxifen, Melphalan, Betulinic acid, L-PDMP, L-PPMP, and GD3 ganglioside. 1545 95

Apoptosis of human breast carcinoma cells (SKBR-3, MCF-7, and MDA-468) has been observed after treatment of these cells with anti-cancer drug cis-platin and glycosphingolipid biosynthesis inhibitor L- and D-PPMP, respectively. These drugs initiated apoptosis in a dose-dependent manner as measured by phenotypic morphological changes, by binding of a fluorescent phophatidyl serine-specific dye (PSS-380) onto the outer leaflet of the cell membranes, and by activation of caspases, -3, -8, and -9. It was observed that in two hours very little apoptotic process had started but predominant biochemical changes occurred after 6 h. DNA degradation started after 24 hours of drug treatment. However, very little is known about the stability of the ';Replication Complexes'' during the apoptotic process. DNA helicases are motor proteins that catalyze the melting of genomic DNA during its replication, repair, and recombination processes. Previously, DNA helicase-III was characterized as a component of the replication complexes isolated from embryonic chicken brains as well as breast and colon carcinoma cells. Helicase activities were measured by a novel method (ROME assay), and DNA polymerase-alpha activities were determined by regular chain extension of the nicked ACT-DNA, by determining values obtained from +/- aphidicolin-treated incubation mixtures. In all three breast carcinoma cell lines, a common trend was observed: a decrease of activities of DNA polymerase-alpha and Helicase III. A sharp decrease of activities of the glycolipid sialyltransferases: SAT-2 (CMP-NeuAc; GD3 alpha2-8 sialyltransferase) and SAT-4 (CMP-NeuAc: GM1a alpha2-3 sialyltransferase) was observed in the apoptotic carcinoma cells treated with L-PPMP compared with cis-platin.
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PMID:Apoptosis of human breast carcinoma cells in the presence of cis-platin and L-/D-PPMP: IV. Modulation of replication complexes and glycolipid: Glycosyltransferases. 1669 1


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