The Reactions of H2O2 and GSNO with the Zinc Finger Motif of XPA. Not A Regulatory Mechanism, But No Synergy with Cadmium Toxicity
Autor: | Andrea Hartwig, Wojciech Bal, Aleksandra Witkiewicz-Kucharczyk, Jacek Olędzki, Wojciech Goch |
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Rok vydání: | 2020 |
Předmět: |
Life sciences
biology cadmium oxidation DNA repair Pharmaceutical Science chemistry.chemical_element hydrogen peroxide Zinc Oxidative phosphorylation medicine.disease_cause Analytical Chemistry lcsh:QD241-441 S-Nitrosoglutathione 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine lcsh:Organic chemistry ddc:570 Drug Discovery DNA Repair Protein medicine S-nitrosoglutathione Physical and Theoretical Chemistry 030304 developmental biology Zinc finger 0303 health sciences Cadmium zinc Organic Chemistry zinc fingers chemistry Chemistry (miscellaneous) Biophysics Molecular Medicine 030217 neurology & neurosurgery Oxidative stress |
Zdroj: | Molecules, 25 (18), Art. Nr.: 4177 Molecules Volume 25 Issue 18 Molecules, Vol 25, Iss 4177, p 4177 (2020) |
ISSN: | 1420-3049 |
Popis: | 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 H2O2 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. |
Databáze: | OpenAIRE |
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