Methionine oxidation as a major cause of the functional impairment of oxidized actin

Dalle‐Donne, Isabella; Rossi, Ranieri; Giustarini, Daniela; Gagliano, Nicoletta; Simplicio, P. Di; Colombo, Roberto; Milzani, Aldo

doi:10.1016/s0891-5849(02)00799-2

Cited by 127 publications

(111 citation statements)

References 42 publications

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“…Our list of identified oxidation sites contains known sites such as methionines 44, 47, and 190 from cytoplasmic actin (P60709). Met-44 and 47 are the first sites that are oxidized by hydrogen peroxide, and further oxidation of Met-190 causes depolymerization of actin filaments (31). Of note is that we here noticed that Met-44 and 47 were oxidized to about 20% and Met-190 only to 10%.…”

Section: A Cofradic Methods For Isolating Peptides Containingsupporting

confidence: 49%

Redox Proteomics of Protein-bound Methionine Oxidation

Ghesquière

Jonckheere

Colaert

et al. 2011

Molecular & Cellular Proteomics

127

160

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We here present a new method to measure the degree of protein-bound methionine sulfoxide formation at a proteome-wide scale. In human Jurkat cells that were stressed with hydrogen peroxide, over 2000 oxidationsensitive methionines in more than 1600 different proteins were mapped and their extent of oxidation was quantified. Meta-analysis of the sequences surrounding the oxidized methionine residues revealed a high preference for neighboring polar residues. Using synthetic methionine sulfoxide containing peptides designed according to the observed sequence preferences in the oxidized Jurkat proteome, we discovered that the substrate specificity of the cellular methionine sulfoxide reductases is a major determinant for the steady-state of methionine oxidation. This was supported by a structural modeling of the MsrA catalytic center. Finally, we applied our method onto a serum proteome from a mouse sepsis model and identi- Reactive oxygen species (ROS)1 are involved in a broad range of processes including signal transduction and gene expression (1), receptor activation (2), antimicrobial and cytotoxic actions of immune cells (3), and aging and age-related degenerative diseases (4). Cellular oxidative stress is associated with increased levels of reactive oxygen species and the molecular damages they cause (5). Of interest here is that some reactive oxygen species specifically modify targeted biomolecules, whereas others cause nonspecific damage. Peroxides for instance are generally more selective compared with hydroxyl radicals (6). Major ROS targets are proteins, with oxidation occurring both at the peptide backbone and at amino acid side-chains (6). The major oxidation product of protein-bound methionine is methionine sulfoxide, further oxidation of which can lead to methionine sulfone, albeit to a much lesser extent (7). The (patho)physiological importance of this modification is reflected by the methionine sulfoxide reductases (Msr) that are present in nearly all organisms (8, 9): decreased activity of these enzymes was associated with aging and Alzheimer disease (10), and abnormal dopamine signaling was recently found in the methionine sulfoxide reductase A knockout mouse (11). Oxidation of methionine can lead to loss of enzyme activity as shown for a brain voltagedependent potassium channel (12). Other studies suggest that methionine oxidation prevents methylation (13) or has an effect on phosphorylation on serines and threonines proximate to the oxidized site (14). In this respect, protein kinases are also targeted by methionine oxidation affecting their activity (e.g. (15)). Further, oxidation of surface methionines increases the protein surface hydrophobicity (16) and may perturb native protein folding, and such oxidized proteins further often become targets for degradation by the proteasome (17).Although methionines are utmost susceptible to oxidation by several types of ROS (18), no adequate proteomic methodologies exist to characterize the exact sites of oxidation and quantify the degree of oxidation. ...

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Section: A Cofradic Methods For Isolating Peptides Containingsupporting

confidence: 49%

Redox Proteomics of Protein-bound Methionine Oxidation

Ghesquière

Jonckheere

Colaert

et al. 2011

Molecular & Cellular Proteomics

127

160

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“…In this context, reactive oxygen species produced on epidermal growth factor stimulation increased G-actin deglutathionylation in A431 cells (50), a modification that increases the rate of actin polymerization, F-actin content, and barbed-end exposure (50,51). As well, it is possible that C2-ceramide may not work in the same manner as endogenous ceramides in inducing insulin resistance, and exogenous C2-ceramide may perturb the membrane structure.…”

Section: Discussionmentioning

confidence: 99%

Ceramide- and Oxidant-Induced Insulin Resistance Involve Loss of Insulin-Dependent Rac-Activation and Actin Remodeling in Muscle Cells

et al. 2007

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In muscle cells, insulin elicits recruitment of the glucose transporter GLUT4 to the plasma membrane. This process engages sequential signaling from insulin receptor substrate (IRS)-1 to phosphatidylinositol (PI) 3-kinase and the serine/threonine kinase Akt. GLUT4 translocation also requires an Akt-independent but PI 3-kinase-and Racdependent remodeling of filamentous actin. Although IRS-1 phosphorylation is often reduced in insulin-resistant states in vivo, several conditions eliciting insulin resistance in cell culture spare this early step. Here, we show that insulin-dependent Rac activation and its consequent actin remodeling were abolished upon exposure of L6 myotubes beginning at doses of C2-ceramide or oxidant-producing glucose oxidase as low as 12.5 mol/l and 12.5 mU/ml, respectively. At 25 mol/l and 25 mU/ml, glucose oxidase and C2-ceramide markedly reduced GLUT4 translocation and glucose uptake and lowered Akt phosphorylation on Ser473 and Thr308, yet they affected neither IRS-1 tyrosine phosphorylation nor its association with p85 and PI 3-kinase activity. Small interfering RNA-dependent Rac1 knockdown prevented actin remodeling and GLUT4 translocation but spared Akt phosphorylation, suggesting that Rac and actin remodeling do not contribute to overall Akt activation. We propose that ceramide and oxidative stress can each affect two independent arms of insulin signaling to GLUT4 at distinct steps, Rac-GTP loading and Akt phosphorylation. Diabetes 56:394 -403, 2007 I nsulin promotes dietary glucose disposal into skeletal muscle through recruitment of GLUT4-containing vesicles to the cell surface. Signaling to GLUT4 requires tyrosine phosphorylation of the insulin receptor substrate (IRS)-1 isoform, which recruits and activates phosphatidylinositol (PI) 3-kinase (1). The latter triggers activation of several serine/threonine kinases, notably Akt, which, through its substrate AS160, regulates GLUT4 vesicle mobilization to and/or fusion with the plasma membrane (2).Along with proper signaling, GLUT4 translocation and stimulation of glucose uptake require dynamic changes in the actin cytoskeleton. Insulin induces actin filament remodeling in mature skeletal muscle (3) and muscle cells in culture (4) that manifest as mesh-like structures beneath the plasma membrane. Actin filament-disrupting drugs (e.g., cytochalasin D and latrunculin B) and actin-stabilizing drugs (e.g., jasplakinolide) inhibit GLUT4 translocation and its consequent glucose uptake in muscle (4,5) and adipose (6,7) cells, as do toxins that inhibit Rho family GTPases that control actin dynamics (8). Interestingly, under these conditions, IRS-1 phosphorylation and PI 3-kinase activity remain unaffected (9 -11). In muscle cells, actin remodeling was also prevented by wortmannin or expression of a dominant-negative mutant of the p85 subunit of class I PI 3-kinase (5), but not by a dominantnegative Akt mutant (12). Hence, insulin signaling bifurcates downstream of PI 3-kinase, one arm leading to actin remodeling and another to Akt activation, bo...

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“…For example, G-actin oxidized by air (41) results in disulfide-bonded dimers that may be incorporated into F-actin filaments during assembly and allow for cross-linking between filaments. In vitro studies of exposure of G-actin to H 2 O 2 showed that several methionine residues may also be oxidized (43,44). Furthermore, oxidation of methionine and cysteine residues produces conformational changes within the actin molecule that may affect the integrity of the assembled F-actin.…”

Section: Discussionmentioning

confidence: 99%

Structure and activity of the axon guidance protein MICAL

Nadella

Bianchet

Gabelli

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

132

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During development, neurons are guided to their targets by shortand long-range attractive and repulsive cues. MICAL, a large multidomain protein, is required for the combined action of semaphorins and plexins in axon guidance. Here, we present the structure of the N-terminal region of MICAL (MICAL fd) determined by x-ray diffraction to 2.0 Å resolution. The structure shows that MICAL fd is an FAD-containing module structurally similar to aromatic hydroxylases and amine oxidases. In addition, we present biochemical data that show that MICAL fd is a flavoenzyme that in the presence of NADPH reduces molecular oxygen to H 2O2 (Km,NAPDH ‫؍‬ 222 M; kcat ‫؍‬ 77 sec ؊1 ), a molecule with known signaling properties. We propose that the H 2O2 produced by this reaction may be one of the signaling molecules involved in axon guidance by MICAL.hydrogen peroxide ͉ hydroxylase ͉ monooxygenase ͉ x-ray diffraction

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Methionine oxidation as a major cause of the functional impairment of oxidized actin

Cited by 127 publications

References 42 publications

Redox Proteomics of Protein-bound Methionine Oxidation

Redox Proteomics of Protein-bound Methionine Oxidation

Ceramide- and Oxidant-Induced Insulin Resistance Involve Loss of Insulin-Dependent Rac-Activation and Actin Remodeling in Muscle Cells

Structure and activity of the axon guidance protein MICAL

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