Protein Glycosylation: Oligosaccharyl Transferase and a Novel Recognition Protein

Noiva, Robert; Kaplan, Howard A.; Geetha-Habib, M; Lennarz, William J.

doi:10.1007/978-3-642-74194-4_11

Cited by 38 publications

(59 citation statements)

References 49 publications

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“…1B was consistent with the cellular distribution of an ER-associated protein. To further examine this point, we compared the localization of ACAT with that of PDI, a protein known to reside in the lumen of almost all of the subcompartments of the ER (22,23). Fig.…”

Section: Acat and Pdi Immunofluorescence Studies In Mousementioning

confidence: 99%

Immunolocalization of Acyl-Coenzyme A:CholesterolO-Acyltransferase in Macrophages

Khelef¹,

Buton²,

Beatini³

et al. 1998

Journal of Biological Chemistry

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Macrophages in atherosclerotic lesions accumulate large amounts of cholesteryl-fatty acyl esters ("foam cell" formation) through the intracellular esterification of cholesterol by acyl-coenzyme A:cholesterol O-acyltransferase (ACAT). In this study, we sought to determine the subcellular localization of ACAT in macrophages. Using mouse peritoneal macrophages and immunofluorescence microscopy, we found that a major portion of ACAT was in a dense reticular cytoplasmic network and in the nuclear membrane that colocalized with the luminal endoplasmic reticulum marker protein-disulfide isomerase (PDI) and that was in a similar distribution as the membrane-bound endoplasmic reticulum marker ribophorin. Remarkably, another portion of the macrophage ACAT pattern did not overlap with PDI or ribophorin, but was found in as yet unidentified cytoplasmic structures that were juxtaposed to the nucleus. Compartments containing labeled ␤-very low density lipoprotein, an atherogenic lipoprotein, did not overlap with the ACAT label, but rather were embedded in the dense reticular network of ACAT. Furthermore, cell-surface biotinylation experiments revealed that freshly harvested, non-attached macrophages, but not those attached to tissue culture dishes, contained ϳ10 -15% of ACAT on the cell surface. In summary, ACAT was found in several sites in macrophages: a cytoplasmic reticular/nuclear membrane site that overlaps with PDI and ribophorin and has the characteristics of the endoplasmic reticulum, a perinuclear cytoplasmic site that does not overlap with PDI or ribophorin and may be another cytoplasmic structure or possibly a unique subcompartment of the endoplasmic reticulum, and a cellsurface site in non-attached macrophages. Understanding possible physiological differences of ACAT in these locations may reveal an important component of ACAT regulation and macrophage foam cell formation.Macrophages enter atherosclerotic lesions at an early stage and are found at all stages of lesion development thereafter (1). Several studies have provided evidence that macrophages play an important role in both lesion initiation and late lesion complications (2, 3). A major property of lesional macrophages is their tendency to become massively loaded with cholesteryl ester, a process known as foam cell formation because the numerous cholesteryl ester droplets give the cells a foamy appearance (1). The pathway by which macrophages accumulate cholesteryl ester is complex and not completely understood. Data from several laboratories suggest that macrophages internalize cholesterol through the uptake of certain "atherogenic" lipoproteins or by direct uptake of lipoprotein cholesterol. When the cellular cholesterol content increases to a certain threshold level, mixed pools of lipoprotein-derived and cellular cholesterol gain access to an integral membrane enzyme called ACAT, 1 which then catalyzes the esterification of the cholesterol to fatty acid via a fatty acyl-CoA intermediate (4).Given the importance of macrophage foam cells in atheroscleros...

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Section: Acat and Pdi Immunofluorescence Studies In Mousementioning

confidence: 99%

Immunolocalization of Acyl-Coenzyme A:CholesterolO-Acyltransferase in Macrophages

Khelef¹,

Buton²,

Beatini³

et al. 1998

Journal of Biological Chemistry

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“…This raises ,~ the question of possible effectors involved in the mechanism of inhibition of the ethanolamine BE activity by prooxidants, especially the importance of the level of lipid hydroxyperoxides and aldehydes (for example 4-hydroxynon-2-enal). It is ~::~o-well known that 4-hydroxyalkenals block thiol groups of pepo ~ ~o " " r~ tides, thus preventing formation of disulfide bridges essential ro o~ o for the enzymatic activity of integral ER proteins [11][12][13]30]. …”

Section: Inhibition Of Enzyme Activity (% Of Control)mentioning

confidence: 99%

“…Introduction capacity to bind to the amino groups of phospholipids and proteins [10], while various lipid peroxidation intermediates, Phosphatidylethanolamine (PE) is one of the major class of by interacting with the evolutionarily conserved redox amino phospholipids in eukaryotic cells, where it constitutes 20~0% acid sequence (-Cys-Gly-Pro-Cys-) of peptides [11], may influof the total phospholipid content of various membranes. Deence enzymatic and transport activities of several integral ER spite de novo synthesis and decarboxylation of phosphatidylmembrane proteins such as thioredoxin [11,12], and protein serine (PS) [1], PE is formed from phosphatidylcholine (PC) disulfide isomerase [13]. or PS by a phospholipid base exchange (BE) reaction, specific…”

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confidence: 99%

Nonenzymatically evoked and cytochrome P450‐dependent lipid peroxidation inhibits synthesis of phosphatidylethanolamine via the ethanolamine base exchange reaction in rat liver microsomes

et al. 1996

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In the present study the relationship between lipid sole pathway for PS formation. Sundler et al. [3] reported that peroxidation, changes in the redox state of membrane and in isolated rat hepatocytes, at physiological concentrations of phosphatidylethanolamine (PE) synthesis via base exchange ethanolamine (25 ~tM), 8-9% of the total PE synthesis could reaction in rat liver microsomes was investigated. It was found be attributed to Ca2+-dependent incorporation of ethanolthat PE synthesis is enhanced in the presence of antioxidants, amine via the BE reaction. The reaction does not result in a butylated hydroxytoluene (BHT), or unsaturated free fatty acids, net increase of the total PE content, but is rather responsible Prooxidants, tert-butyl hydroxyperoxide (BHP), ferrous ions for significant remodelling of preexisting membrane phosphocombined with ascorbate or NADPH (via cytochrome P450-lipids. The most abundant molecular species of PS and PE are dependent proteins), increased the amount of lipid peroxidation known to contain long-chain polyunsaturated fatty acids: araproducts in the membrane, and in consequence inhibited the chidonic (20:4), docosatetraenoic (22:4)and docosahexaenoic reaction. The effect of BHP was fully reversed by reduced (22:6) in the sn-2 position of their glycerol moiety [4]. glutathione and dithiothreitol (DTT), whereas the effect of other compounds could be reversed only by BHT. In contrast, a Furthermore, Ellingson and Seenaiah [5] have documented reversal of the inhibitory effect of cadmium ions on base that stearoyl-polyunsaturated molecular species of PE and exchange activity was observed in the presence of DTT, but PC are preferentially converted to PS by the phospholipid not BHT. Therefore, both the -SH/-S-S-ratio in the membrane, BE reaction in rat liver microsomes. affected by BlIP and cadmium ions, and the lipid hydroxyper-PE, kept in a bilayer configuration by interactions with oxides (rather than aldehydes), generated by ferrous ions and other membrane phospholipid molecules, is able to induce ascorbate or NADPH, are equally responsible for the inactivalocal nonbilayer structures by creating hexagonal phases [6]. tion of the ethanolamine base exchange enzyme in rat liverThis property of PE may be responsible for regulation of the microsomes. This may suggest that the synthesis of PE via the activity of many membranous enzymes, for example cytobase exchange reaction may be considered an element of the chrome P450 [7]. The latter class of enzymes participates in superfine cellular machinery involved in the repair of damage to unsaturated fatty acid chains of phospholipids caused by reactive hydroxylation processes of different hydrophobic molecules, oxygen species under oxidative stress, like fatty and bile acids, phospholipids, steroid hormones and/or xenobiotics [8]. Moreover, the PE hexagonal phase

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“…Although large levels of this enzyme are found in the endoplasmic reticulum, PDI is secreted from cells in which it associates electrostatically with the cell surface (2,3). One of the most studied functions of PDI is its ability to catalyze isomerization and rearrangement of disulfide bonds in the endoplasmic reticulum, contributing to a proper folding of nascent proteins (4). Cell surface PDI was initially discovered in platelets (5), in which it plays a dual role in integrin-mediated adhesion and aggregation (6,7), RSNO-mediated platelet inhibition, and GSNO denitrosation (8).…”

mentioning

confidence: 99%

Characterization of the S-Denitrosation Activity of Protein Disulfide Isomerase

Sliskovic¹,

Raturi²,

Mutus

2005

Journal of Biological Chemistry

142

125

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S-Nitrosoglutathione (GSNO) denitrosation activity of recombinant human protein disulfide isomerase (PDI) has been kinetically characterized by monitoring the loss of the S-NO absorbance, using a NO electrode, and with the aid of the fluorogenic NO x probe 2,3-diaminonaphthalene. The initial rates of denitrosation as a function of [GSNO] displayed hyperbolic behavior irrespective of the method used to monitor denitrosation. The K m values estimated for GSNO were 65 ؎ 5 M and 40 ؎ 10 M for the loss in the S-NO bond and NO production (NO electrode or 2,3-diaminonaphthalene), respectively. Hemoglobin assay provided additional evidence that the final product of PDI-dependent GSNO denitrosation was NO ⅐ . A catalytic mechanism, involving a nitroxyl disulfide intermediate stabilized by imidazole (His 160 a-domain or His 589 a-domain), which after undergoing a one-electron oxidation decomposes to yield NO plus dithiyl radical, has been proposed. Evidence for the formation of thiyl/dithiyl radicals during PDI-catalyzed denitrosation was obtained with 4-((9-acridinecarbonyl)-amino)-2,2,6,6-tetramethylpiperidine-1-oxyl. Evidence has also been obtained showing that in a NO-and O 2 -rich environment, PDI can form N 2 O 3 in its hydrophobic domains. This "NO-charged PDI" can perform intra-and intermolecular S-nitrosation reactions similar to that proposed for serum albumin. Interestingly, reduced PDI was able to denitrosate S-nitrosated PDI (PDI-SNO) resulting in the release of NO. PDI-SNO, once formed, is stable at room temperature in the absence of reducing agent over the period of 2 h. It has been established that PDI is continuously secreted from cells that are net producers of NO-like endothelial cells. The present demonstration that PDI can be S-nitrosated and that PDI-SNO can be denitrosated by PDI suggests that this enzyme could be intimately involved in the transport of intracellular NO equivalents to the cell surface as well as the previous demonstration of PDI in the transfer of S-nitrosothiol-bound NO to the cytosol. Protein disulfide isomerase (PDI)1 was identified about 40 years ago (1). Although large levels of this enzyme are found in the endoplasmic reticulum, PDI is secreted from cells in which it associates electrostatically with the cell surface (2, 3). One of the most studied functions of PDI is its ability to catalyze isomerization and rearrangement of disulfide bonds in the endoplasmic reticulum, contributing to a proper folding of nascent proteins (4). Cell surface PDI was initially discovered in platelets (5), in which it plays a dual role in integrin-mediated adhesion and aggregation (6, 7), RSNO-mediated platelet inhibition, and GSNO denitrosation (8).S-Nitrosothiols (RSNOs) are known nitric oxide (NO) donors. RSNOs range in size from low molecular weight, such as cysteine-NO and homocysteine-NO, to high molecular weight nitrosated proteins, such as serum albumin-NO. They are known to prolong NO half-life (9) and to act as a NO transport system in a cellular environment (10 -12).An additional novel...

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Protein Glycosylation: Oligosaccharyl Transferase and a Novel Recognition Protein

Cited by 38 publications

References 49 publications

Immunolocalization of Acyl-Coenzyme A:CholesterolO-Acyltransferase in Macrophages

Immunolocalization of Acyl-Coenzyme A:CholesterolO-Acyltransferase in Macrophages

Nonenzymatically evoked and cytochrome P450‐dependent lipid peroxidation inhibits synthesis of phosphatidylethanolamine via the ethanolamine base exchange reaction in rat liver microsomes

Characterization of the S-Denitrosation Activity of Protein Disulfide Isomerase

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