Exogenous pyruvate facilitates ultraviolet B-induced DNA damage repair by promoting H3K9 acetylation in keratinocytes and melanocytes

Biomed Pharmacother. 2020 Jun:126:110082. doi: 10.1016/j.biopha.2020.110082. Epub 2020 Mar 9.

Abstract

Ultraviolet radiation (UVR) is the major cause of numerous skin diseases, including sunburn, skin aging, and skin cancers. Pyruvate is a key intermediate in cellular metabolic pathways, which has shown protective effects against oxidative stress and apoptosis, but its role in UV protection remains unclear. Here we established human and mice in vivo model and found that pyruvate protects both human and mouse skin from UVB-induced DNA damage. Moreover, assays in primary keratinocytes and melanocytes further supported the protective role of exogenous pyruvate against UVB-induced DNA damage. Mechanically, pyruvate stimulates the activation of Histone H3 Lysine 9 (H3K9) acetylation, which is an essential step for nucleotide excision repair (NER) pathway. In conclusion, our results suggest that treatment of pyruvate might be an effective strategy to prevent UVB-induced skin diseases.

Keywords: DNA damage repair; H3K9; Histone acetylation; Keratinocyte; Melanocyte; Pyruvate; UVB.

MeSH terms

  • Acetylation
  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • DNA Damage / drug effects*
  • DNA Damage / radiation effects*
  • DNA Repair / drug effects*
  • Histones / metabolism*
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Keratinocytes / radiation effects
  • Melanocytes / drug effects*
  • Melanocytes / metabolism
  • Melanocytes / radiation effects
  • Mice
  • Oxidative Stress
  • Pyruvic Acid / pharmacology*
  • Skin / drug effects
  • Skin / metabolism
  • Skin / pathology
  • Skin / radiation effects
  • Ultraviolet Rays / adverse effects*

Substances

  • Histones
  • Pyruvic Acid