ArticleToxicology and applied pharmacology2019
Peroxynitrite contributes to arsenic-induced PARP-1 inhibition through ROS/RNS generation.
Article in Toxicology and applied pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Arsenic exposure and skin cancer: Mechanisms, clinical evidence and public health implications (Review).International journal of molecular medicine · 2026Review
- The first and second zinc finger domains from Poly-ADP-ribose polymerase 1 (PARP1) are modified by hydrogen sulfide.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026Article
- Liquid‒liquid phase separation and poly(ADP‒ribosyl)ation in the context of ultraviolet radiation-induced stress in mammalian cells.Biophysical reviews · 2025Review
- Update of the risk assessment of inorganic arsenic in food.EFSA journal. European Food Safety Authority · 2024Article
- Mechanisms of genotoxicity and proteotoxicity induced by the metalloids arsenic and antimony.Cellular and molecular life sciences : CMLS · 2023Review
- Arsenic and cancer: Evidence and mechanisms.Advances in pharmacology (San Diego, Calif.) · 2023Article
- Arsenic co-carcinogenesis: Inhibition of DNA repair and interaction with zinc finger proteins.Seminars in cancer biology · 2021Review
- Modulation of PARP activity by Monomethylarsonous (MMAToxicology and applied pharmacology · 2021Article
- Uranium directly interacts with the DNA repair protein poly (ADP-ribose) polymerase 1.Toxicology and applied pharmacology · 2021Article
- Molecular Mechanisms of Arsenic-Induced Disruption of DNA Repair.Chemical research in toxicology · 2020Review
- Biochemical Constituent ofJournal of toxicology · 2020Article
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Arsenic, in the trivalent form (AsIII), is a human co-carcinogen reported to enhance mutagenesis effects of other carcinogens such as UV radiation by inhibiting DNA repair. The zinc finger DNA repair protein Poly (ADP-ribose) polymerase 1 (PARP-1) is a sensitive target of AsIII and both reactive oxygen and nitrogen species (ROS/RNS) generated by AsIII contribute to PARP-1 inhibition. However, the mechanisms of ROS/RNS-mediated PARP inhibition and how AsIII-generated ROS/RNS may be interconnected are still unclear. In this study, we found AsIII exposure of normal human keratinocyte (HEKn) cells generated peroxynitrite through superoxide and nitric oxide production in an AsIII concentration dependent manner. Peroxynitrite inhibited PARP-1 activity and caused zinc loss from PARP-1 protein while scavenging peroxynitrite was protective of the impacts on PARP-1. We identified peroxynitrite was responsible for S-nitrosation on cysteine residues resulting in PARP-1 zinc finger conformational changes. Taken together, the evidence indicates AsIII generates peroxynitrite through superoxide and nitric oxide production, induces S-nitrosation on PARP-1, leading to zinc loss and activity inhibition of PARP-1, thus enhancing DNA damage caused by UV radiation. These findings highlight a role for peroxynitrite as a key molecule of ROS/RNS mediated DNA repair inhibition by AsIII which should inform the development of prevention and intervention strategies against AsIII co-carcinogenesis.
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