Chemiexcited Neurotransmitters and Hormones Create DNA Photoproducts in the Dark

ACS Chem Biol. 2023 Mar 17;18(3):484-493. doi: 10.1021/acschembio.2c00787. Epub 2023 Feb 12.

Abstract

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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA / chemistry
  • DNA Damage*
  • Hormones
  • Mammals / genetics
  • Mammals / metabolism
  • Melanins / genetics
  • Neurotransmitter Agents
  • Peroxynitrous Acid
  • Pyrimidine Dimers / chemistry
  • Ultraviolet Rays*

Substances

  • Melanins
  • Peroxynitrous Acid
  • Pyrimidine Dimers
  • Neurotransmitter Agents
  • Hormones
  • DNA