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Daniel Otzen

Early events in copper-ion catalyzed oxidation of α-synuclein

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Standard

Early events in copper-ion catalyzed oxidation of α-synuclein. / Tiwari, Manish K; Leinisch, Fabian; Sahin, Cagla et al.

In: Free Radical Biology & Medicine, Vol. 121, 06.2018, p. 38-50.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Tiwari, MK, Leinisch, F, Sahin, C, Møller, IM, Otzen, D, Davies, MJ & Bjerrum, MJ 2018, 'Early events in copper-ion catalyzed oxidation of α-synuclein', Free Radical Biology & Medicine, vol. 121, pp. 38-50. https://doi.org/10.1016/j.freeradbiomed.2018.04.559

APA

Tiwari, M. K., Leinisch, F., Sahin, C., Møller, I. M., Otzen, D., Davies, M. J., & Bjerrum, M. J. (2018). Early events in copper-ion catalyzed oxidation of α-synuclein. Free Radical Biology & Medicine, 121, 38-50. https://doi.org/10.1016/j.freeradbiomed.2018.04.559

CBE

Tiwari MK, Leinisch F, Sahin C, Møller IM, Otzen D, Davies MJ, Bjerrum MJ. 2018. Early events in copper-ion catalyzed oxidation of α-synuclein. Free Radical Biology & Medicine. 121:38-50. https://doi.org/10.1016/j.freeradbiomed.2018.04.559

MLA

Tiwari, Manish K et al. "Early events in copper-ion catalyzed oxidation of α-synuclein". Free Radical Biology & Medicine. 2018, 121. 38-50. https://doi.org/10.1016/j.freeradbiomed.2018.04.559

Vancouver

Tiwari MK, Leinisch F, Sahin C, Møller IM, Otzen D, Davies MJ et al. Early events in copper-ion catalyzed oxidation of α-synuclein. Free Radical Biology & Medicine. 2018 Jun;121:38-50. Epub 2018 Apr 21. doi: 10.1016/j.freeradbiomed.2018.04.559

Author

Tiwari, Manish K ; Leinisch, Fabian ; Sahin, Cagla et al. / Early events in copper-ion catalyzed oxidation of α-synuclein. In: Free Radical Biology & Medicine. 2018 ; Vol. 121. pp. 38-50.

Bibtex

@article{234981858d4f4c1196613f8595e0040b,
title = "Early events in copper-ion catalyzed oxidation of α-synuclein",
abstract = "Previous studies on metal-ion catalyzed oxidation of α-synuclein oxidation have mostly used conditions that result in extensive modification precluding an understanding of the early events in this process. In this study, we have examined time-dependent oxidative events related to α-synuclein modification using six different molar ratios of Cu2+/H2O2/protein and Cu2+/H2O2/ascorbate/protein resulting in mild to moderate extents of oxidation. For a Cu2+/H2O2/protein molar ratio of 2.3:7.8:1 only low levels of carbonyls were detected (0.078 carbonyls per protein), whereas a molar ratio of 4.7:15.6:1 gave 0.22 carbonyls per α-synuclein within 15min. With the latter conditions, rapid conversion of 3 out of 4 methionines (Met) to methionine sulfoxide, and 2 out of 4 tyrosines (Tyr) were converted to products including inter- and intra-molecular dityrosine cross-links and protein oligomers, as determined by SDS-PAGE and Western blot analysis. Limited histidine (His) modification was observed. The rapid formation of dityrosine cross-links was confirmed by fluorescence and mass-spectrometry. These data indicate that Met and Tyr oxidation are early events in Cu2+/H2O2-mediated damage, with carbonyl formation being a minor process. With the Cu2+/H2O2/ascorbate system, rapid protein carbonyl formation was detected with the first 5min, but after this time point, little additional carbonyl formation was detected. With this system, lower levels of Met and Tyr oxidation were detected (2 Met and 1 Tyr modified with a Cu2+/H2O2/ascorbate/protein ratio of 2.3:7.8:7.8:1), but greater His oxidation. Only low levels of intra- dityrosine cross-links and no inter- dityrosine oligomers were detected under these conditions, suggesting that ascorbate limits Cu2+/H2O2-induced α-synuclein modification.",
author = "Tiwari, {Manish K} and Fabian Leinisch and Cagla Sahin and M{\o}ller, {Ian Max} and Daniel Otzen and Davies, {Michael J} and Bjerrum, {Morten J}",
note = "Copyright {\textcopyright} 2018. Published by Elsevier Inc.",
year = "2018",
month = jun,
doi = "10.1016/j.freeradbiomed.2018.04.559",
language = "English",
volume = "121",
pages = "38--50",
journal = "Free Radical Biology & Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",

}

RIS

TY - JOUR

T1 - Early events in copper-ion catalyzed oxidation of α-synuclein

AU - Tiwari, Manish K

AU - Leinisch, Fabian

AU - Sahin, Cagla

AU - Møller, Ian Max

AU - Otzen, Daniel

AU - Davies, Michael J

AU - Bjerrum, Morten J

N1 - Copyright © 2018. Published by Elsevier Inc.

PY - 2018/6

Y1 - 2018/6

N2 - Previous studies on metal-ion catalyzed oxidation of α-synuclein oxidation have mostly used conditions that result in extensive modification precluding an understanding of the early events in this process. In this study, we have examined time-dependent oxidative events related to α-synuclein modification using six different molar ratios of Cu2+/H2O2/protein and Cu2+/H2O2/ascorbate/protein resulting in mild to moderate extents of oxidation. For a Cu2+/H2O2/protein molar ratio of 2.3:7.8:1 only low levels of carbonyls were detected (0.078 carbonyls per protein), whereas a molar ratio of 4.7:15.6:1 gave 0.22 carbonyls per α-synuclein within 15min. With the latter conditions, rapid conversion of 3 out of 4 methionines (Met) to methionine sulfoxide, and 2 out of 4 tyrosines (Tyr) were converted to products including inter- and intra-molecular dityrosine cross-links and protein oligomers, as determined by SDS-PAGE and Western blot analysis. Limited histidine (His) modification was observed. The rapid formation of dityrosine cross-links was confirmed by fluorescence and mass-spectrometry. These data indicate that Met and Tyr oxidation are early events in Cu2+/H2O2-mediated damage, with carbonyl formation being a minor process. With the Cu2+/H2O2/ascorbate system, rapid protein carbonyl formation was detected with the first 5min, but after this time point, little additional carbonyl formation was detected. With this system, lower levels of Met and Tyr oxidation were detected (2 Met and 1 Tyr modified with a Cu2+/H2O2/ascorbate/protein ratio of 2.3:7.8:7.8:1), but greater His oxidation. Only low levels of intra- dityrosine cross-links and no inter- dityrosine oligomers were detected under these conditions, suggesting that ascorbate limits Cu2+/H2O2-induced α-synuclein modification.

AB - Previous studies on metal-ion catalyzed oxidation of α-synuclein oxidation have mostly used conditions that result in extensive modification precluding an understanding of the early events in this process. In this study, we have examined time-dependent oxidative events related to α-synuclein modification using six different molar ratios of Cu2+/H2O2/protein and Cu2+/H2O2/ascorbate/protein resulting in mild to moderate extents of oxidation. For a Cu2+/H2O2/protein molar ratio of 2.3:7.8:1 only low levels of carbonyls were detected (0.078 carbonyls per protein), whereas a molar ratio of 4.7:15.6:1 gave 0.22 carbonyls per α-synuclein within 15min. With the latter conditions, rapid conversion of 3 out of 4 methionines (Met) to methionine sulfoxide, and 2 out of 4 tyrosines (Tyr) were converted to products including inter- and intra-molecular dityrosine cross-links and protein oligomers, as determined by SDS-PAGE and Western blot analysis. Limited histidine (His) modification was observed. The rapid formation of dityrosine cross-links was confirmed by fluorescence and mass-spectrometry. These data indicate that Met and Tyr oxidation are early events in Cu2+/H2O2-mediated damage, with carbonyl formation being a minor process. With the Cu2+/H2O2/ascorbate system, rapid protein carbonyl formation was detected with the first 5min, but after this time point, little additional carbonyl formation was detected. With this system, lower levels of Met and Tyr oxidation were detected (2 Met and 1 Tyr modified with a Cu2+/H2O2/ascorbate/protein ratio of 2.3:7.8:7.8:1), but greater His oxidation. Only low levels of intra- dityrosine cross-links and no inter- dityrosine oligomers were detected under these conditions, suggesting that ascorbate limits Cu2+/H2O2-induced α-synuclein modification.

U2 - 10.1016/j.freeradbiomed.2018.04.559

DO - 10.1016/j.freeradbiomed.2018.04.559

M3 - Journal article

C2 - 29689296

VL - 121

SP - 38

EP - 50

JO - Free Radical Biology & Medicine

JF - Free Radical Biology & Medicine

SN - 0891-5849

ER -