Involvement of Glycosylphosphatidylinositol-linked Ceruloplasmin in the Copper/Zinc-Nitric Oxide-dependent Degradation of Glypican-1 Heparan Sulfate in Rat C6 Glioma Cells

Mani, Katrin; Cheng, Fang; Havsmark, Birgitta; David, Samuel; Fransson, Lars‐Âke

doi:10.1074/jbc.m313678200

Cited by 28 publications

(22 citation statements)

References 26 publications

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“…S-nitrosylation is another important post-transcriptional modification of the APPs and their peptides, which may be involved in NO-dependent signal transductions. For example, a recent study indicates that S-nitrosylation can be effectively catalyzed by the copper ion of ceruloplasmin, a major multicopper-containing plasma protein, under physiological conditions (Mani et al, 2004). It is now also conceivable that nitrosylation of thiols is involved in modulation of various biological events, such as functional regulation of receptors, ion channels and synaptic vesicle fusion (Miyamoto et al, 2000).…”

Section: Oxidized and Nitrosylated Forms Of Appsmentioning

confidence: 99%

Acute Phase Proteins: Structure and Function Relationship

Janciauskiene¹,

Welte²,

Mahadeva³

2011

Acute Phase Proteins - Regulation and Functions of Acute Phase Proteins

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Section: Oxidized and Nitrosylated Forms Of Appsmentioning

confidence: 99%

Acute Phase Proteins: Structure and Function Relationship

Janciauskiene¹,

Welte²,

Mahadeva³

2011

Acute Phase Proteins - Regulation and Functions of Acute Phase Proteins

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“…For example, binding of iNOS to COX2 is required for S-nitrosylation and activation of prostaglandin synthesis (13), whereas the subcellular localization of endothelial NOS is a major determinant of S-nitrosylation-mediated protein trafficking (25). Moreover, although it is generally assumed that S-nitrosylation reactions are nonenzymatic, there is precedence for hemoglobin-dependent S-nitrosylation of the anion exchanger protein AE1 (26) and ceruloplasmin-dependent S-nitrosylation of glypican-1 (27) and GSH (28), consistent with a recent report that metalloproteins may play a general role in SNO synthesis (29).…”

mentioning

confidence: 99%

Thioredoxin-interacting Protein (Txnip) Is a Feedback Regulator of S-Nitrosylation

Forrester

Seth

Hausladen

et al. 2009

Journal of Biological Chemistry

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Nitric oxide exerts a plethora of biological effects via protein S-nitrosylation, a redox-based reaction that converts a protein Cys thiol to a S-nitrosothiol. However, although the regulation of protein S-nitrosylation has been the subject of extensive study, much less is known about the systems governing protein denitrosylation. Most recently, thioredoxin/thioredoxin reductases were shown to mediate both basal and stimulus-coupled protein denitrosylation. We now demonstrate that protein denitrosylation by thioredoxin is regulated dynamically by thioredoxin-interacting protein (Txnip), a thioredoxin inhibitor. Endogenously synthesized nitric oxide represses Txnip, thereby facilitating thioredoxin-mediated denitrosylation. Autoregulation of denitrosylation thus allows cells to survive nitrosative stress. Our findings reveal that denitrosylation of proteins is dynamically regulated, establish a physiological role for thioredoxin in protection from nitrosative stress, and suggest new approaches to manipulate cellular S-nitrosylation.It has become increasingly appreciated that protein S-nitrosylation, the covalent attachment of a nitroso group to a cysteine thiol side chain, is a principle mechanism by which nitric oxide modulates numerous cellular functions and phenotypes (1, 2). These include G-protein-coupled receptor signaling (3-5), death receptor-mediated apoptosis (6 -9), vesicular trafficking (10 -12), stimulation of prostaglandin synthesis (13-15), hypoxia-dependent control of blood flow (16 -18), and the unfolded protein response (19). In addition, aberrant S-nitrosylation is implicated in pathologies such as tumor initiation and growth (20, 21), neurodegeneration (19,22,23), and pulmonary hypertension (24).The three isoforms of nitric-oxide synthase (neuronal NOS/ NOS1, iNOS/NOS2, 2 and endothelial NOS/NOS3) are well established mediators of S-nitrosylation, and numerous studies have demonstrated that their localization is critical for S-nitrosylation of target proteins. For example, binding of iNOS to COX2 is required for S-nitrosylation and activation of prostaglandin synthesis (13), whereas the subcellular localization of endothelial NOS is a major determinant of S-nitrosylation-mediated protein trafficking (25). Moreover, although it is generally assumed that S-nitrosylation reactions are nonenzymatic, there is precedence for hemoglobin-dependent S-nitrosylation of the anion exchanger protein AE1 (26) and ceruloplasmin-dependent S-nitrosylation of glypican-1 (27) and GSH (28), consistent with a recent report that metalloproteins may play a general role in SNO synthesis (29).By contrast with progress in elucidating the enzymatic determinants of S-nitrosylation, the intracellular mediators of denitrosylation and their possible contributions to overall Snitrosylation status have only recently gained attention. By analogy to phosphorylation (where kinases and phosphatases together regulate phosphorylation), the steady-state level of S-nitrosylation is the net difference between nitrosylation and denitros...

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“…First, cysteines in the Gpc-1 core protein are S-nitrosylated (nitric oxide (NO) is added) by endogenously formed nitric oxide (NO) in a Cu(II)-dependent redox reaction (33)(34)(35). Free copper ions are scarce in vivo, but Cu(II)-loaded cuproproteins, such as the glycosylphosphatidylinositol-anchored ceruloplasmin (36) and prion proteins (34,37) as well as APP, can support S-nitrosylation of Gpc-1. Moreover, APP and Gpc-1 colocalize in subcellular compartments of neuroblastoma cells (38).…”

mentioning

confidence: 99%

Suppression of Amyloid β A11 Antibody Immunoreactivity by Vitamin C

Cheng

Cappai

Ciccotosto

et al. 2011

Journal of Biological Chemistry

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Amyloid ␤ (A␤) is generated from the copper-and heparan sulfate (HS)-binding amyloid precursor protein (APP) by proteolytic processing. APP supports S-nitrosylation of the HS proteoglycan glypican-1 (Gpc-1). In the presence of ascorbate, there is NO-catalyzed release of anhydromannose (anMan)-containing oligosaccharides from Gpc-1-nitrosothiol. We investigated whether these oligosaccharides interact with A␤ during APP processing and plaque formation. anMan immunoreactivity was detected in amyloid plaques of Alzheimer (AD) and APP transgenic (Tg2576) mouse brains by immunofluorescence microscopy. APP/APP degradation products detected by antibodies to the C terminus of APP, but not A␤ oligomers detected by the anti-A␤ A11 antibody, colocalized with anMan immunoreactivity in Tg2576 fibroblasts. A 50 -55-kDa anionic, sodium dodecyl sulfate-stable, anMan-and A␤-immunoreactive species was obtained from Tg2576 fibroblasts using immunoprecipitation with anti-APP (C terminus). anMan-containing HS oligo-and disaccharide preparations modulated or suppressed A11 immunoreactivity and oligomerization of A␤42 peptide in an in vitro assay. A11 immunoreactivity increased in Tg2576 fibroblasts when Gpc-1 autoprocessing was inhibited by 3-␤[2(diethylamino)ethoxy]androst-5-en-17-one (U18666A) and decreased when Gpc-1 autoprocessing was stimulated by ascorbate. Neither overexpression of Gpc-1 in Tg2576 fibroblasts nor addition of copper ion and NO donor to hippocampal slices from 3xTg-AD mice affected A11 immunoreactivity levels. However, A11 immunoreactivity was greatly suppressed by the subsequent addition of ascorbate. We speculate that temporary interaction between the A␤ domain and small, anMan-containing oligosaccharides may preclude formation of toxic A␤ oligomers. A portion of the oligosaccharides are co-secreted with the A␤ peptides and deposited in plaques. These results support the notion that an inadequate supply of vitamin C could contribute to late onset AD in humans. The amyloid ␤ (A␤)3 peptides that have a central role in Alzheimer disease (AD) are derived from the amyloid precursor protein (APP). APP is a copper-and heparan sulfate (HS)-binding membrane protein, which is expressed in many cell types, including neural cells and fibroblasts (1-4). Processing of APP involves several proteases and regulatory proteins, collectively designated ␣-, ␤-, and ␥-secretases (supplemental Fig. S1, a-c). Single ␣-or ␤-cleavages result in the release of the large ectodomain, whereas the C-terminal fragments (APP-CTF-␣ and APP-CTF-␤, respectively) remain tethered to the membrane. Combined ␤-and ␥-cleavages are amyloidogenic and lead to release of the C-terminal cytoplasmic domain of APP and the generation of A␤ peptides, mostly A␤40 and A␤42. A␤ peptides first form soluble oligomers and then insoluble aggregates that accumulate as amyloid fibrils and senile plaques in the brain of AD patients. Soluble A␤ oligomers formed at early stages of AD are believed to be particularly toxic and responsible for early memory failure (5-9).Cell ...

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Involvement of Glycosylphosphatidylinositol-linked Ceruloplasmin in the Copper/Zinc-Nitric Oxide-dependent Degradation of Glypican-1 Heparan Sulfate in Rat C6 Glioma Cells

Cited by 28 publications

References 26 publications

Acute Phase Proteins: Structure and Function Relationship

Acute Phase Proteins: Structure and Function Relationship

Thioredoxin-interacting Protein (Txnip) Is a Feedback Regulator of S-Nitrosylation

Suppression of Amyloid β A11 Antibody Immunoreactivity by Vitamin C

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