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The Reactions of H$_{2}$O$_{2}$ and GSNO with the Zinc Finger Motif of XPA. Not A Regulatory Mechanism, but No Synergy with Cadmium Toxicity

Witkiewicz-Kucharczyk, Aleksandra; Goch, Wojciech; Olędzki, Jacek; Hartwig, Andrea; Bal, Wojciech

Abstract:
Tetrathiolate zinc fingers are potential targets of oxidative assault under cellular stress conditions. We used the synthetic 37-residue peptide representing the tetrathiolate zinc finger domain of the DNA repair protein XPA, acetyl-DYVICEECGKEFMSYLMNHFDLPTCDNCRDADDKHK-amide (XPAzf) as a working model to study the reaction of its Zn(II) complex (ZnXPAzf) with hydrogen peroxide and S-nitrosoglutathione (GSNO), as oxidative and nitrosative stress agents, respectively. We also used the Cd(II) substituted XPAzf (CdXPAzf) to assess the situation of cadmium assault, which is accompanied by oxidative stress. Using electrospray mass spectrometry (ESI-MS), HPLC, and UV-vis and circular dichroism spectroscopies we demonstrated that even very low levels of H$_{2}$O$_{2}$ and GSNO invariably cause irreversible thiol oxidation and concomitant Zn(II) release from ZnXPAzf. In contrast, CdXPAzf was more resistant to oxidation, demonstrating the absence of synergy between cadmium and oxidative stresses. Our results indicate that GSNO cannot act as a reversible modifier of XPA, and rather has a deleterious effect on DNA repair.

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Verlagsausgabe §
DOI: 10.5445/IR/1000126915
Veröffentlicht am 28.11.2020
Originalveröffentlichung
DOI: 10.3390/molecules25184177
Scopus
Zitationen: 1
Web of Science
Zitationen: 1
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Angewandte Biowissenschaften (IAB)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2020
Sprache Englisch
Identifikator ISSN: 1420-3049
KITopen-ID: 1000126915
Erschienen in Molecules
Band 25
Heft 18
Seiten Art. Nr.: 4177
Vorab online veröffentlicht am 12.09.2020
Schlagwörter zinc fingers, zinc, cadmium, hydrogen peroxide, S-nitrosoglutathione, oxidation
Nachgewiesen in Web of Science
Scopus
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