Chemiexcited Neurotransmitters and Hormones Create DNA Photoproducts in the Dark

Autor(es)

Goncalves, Leticia C. P. ; Angele-Martinez, Carlos ; Premi, Sanjay ; Palmatier, Meg A. ; Prado, Fernanda Manso ; Di Mascio, Paolo ; Bastos, Erick L. ; Brash, Douglas E.

• Tipo de documento: Artigo Científico
• Fonte: ACS Chemical Biology; v. N/A, p. 10-pg., 2023-02-12.

Resumo

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 catechol-amine 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 O2 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. (AU)

• Processo FAPESP: 18/25842-8 - Fontes, Alvos e Respostas Biológicas de Espécies Tripletes e Oxigênio Singlete: Patogenicidade e Supressão.
• Beneficiário: Leticia Christina Pires Gonçalves
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/15412-9 - Conjugados de pigmentos de flores e sílica: materiais híbridos inteligentes e biocompatíveis
• Beneficiário: Erick Leite Bastos
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/12663-1 - Oxigênio singlete e peróxidos em química biológica
• Beneficiário: Paolo Di Mascio
• Modalidade de apoio: Auxílio à Pesquisa - Temático