Sulfinylation on Superoxide Dismutase 1 Cys111: Novel Mechanism for 1-Nitropyrene to Promote Acute Reactive Oxygen Species Generation

Guangshan Xie, Lin Zhu, Yanhao Zhang, Yuanyuan Song, Hongna Zhang, Zhu Yang, Zongwei Cai*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

9 Citations (Scopus)

Abstract

1-Nitropyrene (1-NP) is one of the most representative diesel exhaust-sourced components existing in fine particulate matter (PM2.5) and a potential carcinogen. 1-NP demonstrates a significant higher cytotoxicity than its structural analogs and precursor. Herein, 1-NP with its structural analog 3-nitrofluoranthene and precursor pyrene in human lung epithelial cell lines are compared. An acute reactive oxygen species (ROS) accompanied with cell death is observed for 1-NP. Using compound-centric redox proteomics analysis, it is shown that 1-NP significantly remodeled the redox proteome and specifically targeted on ROS reduction pathway. Superoxide dismutase 1 (SOD1) is identified as a potential target. It is demonstrated that 1-NP directly acts on cysteine residue Cys111 and inhibits SOD activity. The position of nitroxide determines its direct target and contributes to the unique mechanism of 1-NP. A novel mechanism for 1-NP cytotoxicity and ROS induction is therefore proposed.
Original languageEnglish
Article number2000123
Number of pages11
JournalSmall Structures
Volume2
Issue number3
Early online date5 Jan 2021
DOIs
Publication statusPublished - Mar 2021

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