Chemiexcited neurotransmitters and hormones create DNA photoproducts in the dark
Open accessAbstract
In DNA, electron excitation allows adjacent pyrimidine bases to dimerize by [2 + 2] cycloaddition, creating chemically stable but lethal and mutagenic cyclobutane pyrimidine dimers (CPDs). The usual cause is ultraviolet radiation. Alternatively, CPDs can be made in the dark (dCPDs) via chemically mediated electron excitation of the skin pigment melanin, after it is oxidized by peroxynitrite formed from the stress-induced radicals superoxide and nitric oxide. We now show that the dark process is not limited to the unusual structural molecule melanin: signaling biomolecules such as indolamine and catecholamine neurotransmitters and hormones can also be chemiexcited to energy levels high enough to form dCPDs. Oxidation of serotonin, dopamine, melatonin, and related biogenic amines by peroxynitrite created triplet-excited species, evidenced by chemiluminescence, energy transfer to a triplet-state reporter, or transfer to O 2 resulting in singlet molecular oxygen. For a subset of these signaling molecules, triplet states created by peroxynitrite or peroxidase generated dCPDs at levels comparable to ultraviolet (UV). Neurotransmitter catabolism by monoamine oxidase also generated dCPDs. These results reveal a large class of signaling molecules as electronically excitable by biochemical reactions and thus potential players in deviant mammalian metabolism in the absence of light.
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Excited carbonyls differ from ground-state carbonyl stress protein adducts detected by Western blot, which are created by ground-state radicals or dicarbonyls and disrupt protein function by ground-state chemistry.
“Excited carbonyls differ from the ground-state “carbonyl stress” protein adducts detected by Western blot assays, which are created by ground-state radicals or dicarbonyls and then disrupt protein function by ground-state chemistry”
From Chemiexcitation: Mammalian Photochemistry in the Dark<sup>†</sup> (2023) · cites this paper as [45]
The Introduction (page unavailable) distinguishes triplet-excited carbonyl chemistry from ground-state reactions, stating that dark DNA photoproducts cannot be created by ground-state reactions. It does not address Western blot detection of carbonyl-stress protein adducts, their formation by radicals or dicarbonyls, or their effects on protein function. (LLM, conf=0.84)
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Chemiexcitation: Mammalian Photochemistry in the Dark<sup>†</sup>
Brash, D. E., & Goncalves, L. C. P. (2023) · Photochemistry and Photobiology · doi:10.1111/php.13781 · Cited by 16 · see citing works
Self-citation
- Authors
- Gonçalves, L. C. P., Angelé-Martínez, C., Premi, S., Palmatier, M. A., Prado, F. M., Di Mascio, P., Bastos, E. L., & Brash, D. E.
- Affiliations
- Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06520-8040, United States
- Yale University (US)
- Universidade de São Paulo (BR)
- Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-000 São Paulo, São Paulo, Brazil
- Yale Cancer Center (US)
- Corresponding author
- Brash, Douglas E.
- Venue
- ACS Chemical Biology
- Publisher
- American Chemical Society (ACS)
- Published
- 2023-02-13
- Volume
- 18
- Issue
- 3
- Pages
- 484-493
- ISSN
- 1554-8929 (ISSN-L)
- 1554-8937
- PMC
- PMC10276651
- OpenAlex
- W4320493590
- Cited by
- 15
- References
- 52
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 5
- FWCI
- 2.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- ACS Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Yale Cancer Center
- Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (302120/2018-1)
- Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo (2013/07937-8, ELB2019/15412-9, LCPG2018/25842-8, PDM2012/12663-1)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (1R01AR070851)
- John Simon Guggenheim Memorial Foundation
- Topics
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Photochemistry and Electron Transfer Studies
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- DNA photoproducts, cyclobutane pyrimidine dimers, chemiexcitation, peroxynitrite, indolamines, catecholamines, serotonin, dopamine, melatonin, biogenic amines, triplet state, singlet oxygen, melanin, monoamine oxidase, neurotransmitters, hormones, chemiluminescence
- MeSH terms
- Animals, DNA, DNA Damage, Hormones, Mammals, Melanins, Pyrimidine Dimers, Ultraviolet Rays, Neurotransmitter Agents, Peroxynitrous Acid
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