Methionine Sulfoxide Reductases Preferentially Reduce Unfolded Oxidized Proteins and Protect Cells from Oxidative Protein Unfolding

Tarrago, Lionel; Kaya, Alaattin; Weerapana, Eranthie; Marino, Stefano M.; Gladyshev, Vadim N.

doi:10.1074/jbc.m112.374520

Cited by 79 publications

(117 citation statements)

References 46 publications

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“…MsrA has historically been considered a reductase, not an ROS scavenger (41,59). In spite of its impressive cytoprotection and antioxidation (5,42,44,72,73), the precise mechanisms and fundamental chemical principles for MsrAmediated antioxidation remain largely unclear.…”

Section: Discussionmentioning

confidence: 99%

Methionine Sulfoxide Reductase A Negatively Controls Microglia-Mediated Neuroinflammation via Inhibiting ROS/MAPKs/NF-κB Signaling Pathways Through a Catalytic Antioxidant Function

Fan

Zhang

et al. 2015

Antioxidants & Redox Signaling

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Aims: Oxidative burst is one of the earliest biochemical events in the inflammatory activation of microglia. Here, we investigated the potential role of methionine sulfoxide reductase A (MsrA), a key antioxidant enzyme, in the control of microglia-mediated neuroinflammation. Results: MsrA was detected in rat microglia and its expression was upregulated on microglial activation. Silencing of MsrA exacerbated lipopolysaccharide (LPS)-induced activation of microglia and the production of inflammatory markers, indicating that MsrA may function as an endogenous protective mechanism for limiting uncontrolled neuroinflammation. Application of exogenous MsrA by transducing Tat-rMsrA fusion protein into microglia attenuated LPS-induced neuroinflammatory events, which was indicated by an increased Iba1 (a specific microglial marker) expression and the secretion of pro-inflammatory cytokines, and this attenuation was accompanied by inhibiting multiple signaling pathways such as p38 and ERK mitogen-activated protein kinases (MAPKs) and nuclear factor kappaB (NF-jB). These effects were due to MsrA-mediated reactive oxygen species (ROS) elimination, which may be derived from a catalytic effect of MsrA on the reaction of methionine with ROS. Furthermore, the transduction of Tat-rMsrA fusion protein suppressed the activation of microglia and the expression of pro-inflammatory factors in a rat model of neuroinflammation in vivo. Innovation: This study provides the first direct evidence for the biological significance of MsrA in microglia-mediated neuroinflammation. Conclusion: Our data provide a profound insight into the role of endogenous antioxidative defense systems such as MsrA in the control of microglial function. Antioxid. Redox Signal. 22, 832-847.

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Section: Discussionmentioning

confidence: 99%

Methionine Sulfoxide Reductase A Negatively Controls Microglia-Mediated Neuroinflammation via Inhibiting ROS/MAPKs/NF-κB Signaling Pathways Through a Catalytic Antioxidant Function

Fan

Zhang

et al. 2015

Antioxidants & Redox Signaling

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“…These protective effects were dependent upon MsrA, indicating that the antioxidant effects of AS-IV are associated with MsrA. Previous studies have demonstrated that the loss of MsrA renders cells hypersensitive to damage by H 2 O 2 , nitrite and S-nitrosogluthatione, and results in the accumulation of higher levels of oxidized proteins (13,15,17,18,42). In addition, AS-IV has been identified to confer increased resistance to oxidative stress (18,21).…”

Section: Discussionmentioning

confidence: 98%

“…MsrA repairs oxidatively-damaged proteins and functions as an antioxidant enzyme (16,18). To investigate whether MsrA is associated with the protective effect of AS-IV, protein levels of MsrA after MPP + -induced oxidative damage with or without AS-IV were measured using western blotting (Fig.…”

Section: As-iv Rescues Msra Protein Expression After Mppmentioning

confidence: 99%

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Astragaloside IV rescues MPP+-induced mitochondrial dysfunction through upregulation of methionine sulfoxide reductase A

Liu

et al. 2017

Experimental and Therapeutic Medicine

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“…Met oxidation can be reversed by NADPHdependent MetO reductases (Msr), which have been identified in all organisms from bacteria to mammals [11]. Currently, three classes of Msr are discovered:…”

Section: Met Oxidation (Met Sulfoxide)mentioning

confidence: 99%

Methionine And Antioxidant Potential

Yin

2016

JAA

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Methionine (Met) is a nutritionally essential amino acid and has been widely demonstrated to improve cellular oxidative balance and mediate oxidative stress. Met targets reactive oxygen species (ROS) directly by being oxidized to Met sulfoxide (MetO) [1]. Met can be metabolized to cysteine (Cys) through transsulfuration pathway, which is further metabolized to glutathione (GSH), taurine, and hydrogen sulfide (H 2 S). All these metabolites exhibit antioxidant functions in various models (reviewed at [2]). More recently, Met also has been demonstrated to enhance cellular oxidative tolerance via pentose phosphate pathway (PPP) [3], which contributes to the balance of cellular reducing power and accelerates the reduction reaction of MetO and GSH oxidative product GSSH back to Met and GSH.

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Methionine Sulfoxide Reductases Preferentially Reduce Unfolded Oxidized Proteins and Protect Cells from Oxidative Protein Unfolding

Cited by 79 publications

References 46 publications

Methionine Sulfoxide Reductase A Negatively Controls Microglia-Mediated Neuroinflammation via Inhibiting ROS/MAPKs/NF-κB Signaling Pathways Through a Catalytic Antioxidant Function

Methionine Sulfoxide Reductase A Negatively Controls Microglia-Mediated Neuroinflammation via Inhibiting ROS/MAPKs/NF-κB Signaling Pathways Through a Catalytic Antioxidant Function

Astragaloside IV rescues MPP+-induced mitochondrial dysfunction through upregulation of methionine sulfoxide reductase A

Methionine And Antioxidant Potential

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