+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Oxidant-induced Interprotein Disulfide Formation in Cardiac Protein DJ-1 Occurs via an Interaction with Peroxiredoxin 2



Oxidant-induced Interprotein Disulfide Formation in Cardiac Protein DJ-1 Occurs via an Interaction with Peroxiredoxin 2



Journal of Biological Chemistry 291(19): 10399-10410



The role and responses of the dimeric DJ-1 protein to cardiac oxidative stress is incompletely understood. H2O2 induces a 50-kDa DJ-1 interprotein homodimer disulfide, known to form between Cys-53 on each subunit. A trimeric 75-kDa DJ-1 complex that mass spectrometry shows contained 2-Cys peroxiredoxin also formed and precedes the appearance of the disulfide dimer. These observations may represent peroxiredoxin sensing and transducing the oxidant signal to DJ-1. The dimeric disulfide DJ-1 complex was stabilized by auranofin, suggesting that thioredoxin recycles it in cells. Higher concentrations of H2O2 concomitantly induce DJ-1 Cys-106 hyperoxidation (sulfination or sulfonation) in myocytes, perfused heart, or HEK cells. An oxidation-resistant C53A DJ-1 shows potentiated H2O2-induced Cys-106 hyperoxidation. DJ-1 also forms multiple disulfides with unknown target proteins during H2O2 treatment, the formation of which is also potentiated in cells expressing the C53A mutant. This suggests that the intersubunit disulfide induces a conformational change that limits Cys-106 forming heterodisulfide protein complexes or from hyperoxidizing. High concentrations of H2O2 also induce cell death, with DJ-1 Cys-106 sulfonation appearing causal in these events, as expressionof C53A DJ-1 enhanced both Cys-106 sulfonation and cell death. Nonetheless, expression of the DJ-1 C106A mutant, which fully prevents hyperoxidation, also showed exacerbated cell death responses to H2O2 A rational explanation for these findings is that DJ-1 Cys-106 forms disulfides with target proteins to limit oxidant-induced cell death. However, when Cys-106 is hyperoxidized, formation of these potentially protective heterodimeric disulfide complexes is limited, and so cell death is exacerbated.

(PDF emailed within 0-6 h: $19.90)

Accession: 058488160

Download citation: RISBibTeXText

PMID: 26945066

DOI: 10.1074/jbc.M115.699850


Related references

Oxidant-induced activation of type I protein kinase A is mediated by RI subunit interprotein disulfide bond formation. Journal of Biological Chemistry 281(31): 21827-21836, 2006

Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo: the protective effect of allopurinol. Journal of Pharmacology and Experimental Therapeutics 255(3): 935-941, 1990

Activation of the heterodimeric central complex SoxYZ of chemotrophic sulfur oxidation is linked to a conformational change and SoxY-Y interprotein disulfide formation. Biochemistry 46(38): 10990-8, 2007

Protein-disulfide isomerase-mediated reduction of two disulfide bonds of HIV envelope glycoprotein 120 occurs post-CXCR4 binding and is required for fusion. Journal of Biological Chemistry 278(5): 3131-3136, 2002

Hyperoxidized peroxiredoxin 2 interacts with the protein disulfide- isomerase ERp46. Biochemical Journal 453(3): 475-485, 2013

Peroxiredoxin Ahp1 acts as a receptor for alkylhydroperoxides to induce disulfide bond formation in the Cad1 transcription factor. Journal of Biological Chemistry 285(14): 10597-10604, 2010

The effect of calmodulin inhibitors and the new cardiotonic drug DPI 201-106 on the formation of interprotein bonds in the cardiac troponin complex. Biokhimiia 55(7): 1251-1256, 1990

Effect of calmodulin inhibitors and the new cardiotonic drug dpi 201 106 on interprotein bond formation within the cardiac troponin complex. Biokhimiya 55(7): 1251-1256, 1990

Prion protein interaction with glycosaminoglycan occurs with the formation of oligomeric complexes stabilized by Cu(II) bridges. Journal of Molecular Biology 319(2): 527-540, 2002

Oxidant injury occurs rapidly after cardiac arrest, cardiopulmonary resuscitation, and reperfusion. Critical Care Medicine 33(9): 2043-2048, 2005

The interaction of thioredoxin with Txnip. Evidence for formation of a mixed disulfide by disulfide exchange. Journal of Biological Chemistry 281(31): 21884-21891, 2006

Oxidant sensing by reversible disulfide bond formation. Journal of Biological Chemistry 288(37): 26489-26496, 2013

Increased cardiac protein synthesis occurs acutely however decreased degradation occurs chronically in aortic regurgitation. Clinical Research 36(3): 543A, 1988

Streptozotocin-induced diabetes increases disulfide bond formation on cardiac ryanodine receptor (RyR2). Journal of Pharmacology and Experimental Therapeutics 305(3): 989-998, 2003

Ascorbate oxidase, protein disulfide isomerase, ascorbic acid, dehydroascorbic acid and protein levels in developing wheat kernels and their relationship to protein disulfide bond formation. Cereal Chemistry 80(1): 35-39, 2003