Discovery of the Involvement in DNA Oxidative Damage of Human Sperm Nuclear Basic Proteins of Healthy Young Men Living in Polluted Areas

Int J Mol Sci. 2020 Jun 12;21(12):4198. doi: 10.3390/ijms21124198.

Abstract

DNA oxidative damage is one of the main concerns being implicated in severe cell alterations, promoting different types of human disorders and diseases. For their characteristics, male gametes are the most sensitive cells to the accumulation of damaged DNA. We have recently reported the relevance of arginine residues in the Cu(II)-induced DNA breakage of sperm H1 histones. In this work, we have extended our previous findings investigating the involvement of human sperm nuclear basic proteins on DNA oxidative damage in healthy males presenting copper and chromium excess in their semen. We found in 84% of those males an altered protamines/histones ratio and a different DNA binding mode even for those presenting a canonical protamines/histones ratio. Furthermore, all the sperm nuclear basic proteins from these samples that resulted were involved in DNA oxidative damage, supporting the idea that these proteins could promote the Fenton reaction in DNA proximity by increasing the availability of these metals near the binding surface of DNA. In conclusion, our study reveals a new and unexpected behavior of human sperm nuclear basic proteins in oxidative DNA damage, providing new insights for understanding the mechanisms related to processes in which oxidative DNA damage is implicated.

Keywords: DNA oxidative damage; EMSA; fluorescence; heavy metals; human protamines; protein–DNA binding.

MeSH terms

  • Arginine / analysis*
  • Copper / analysis*
  • DNA / genetics*
  • DNA / metabolism
  • Environmental Pollution / adverse effects
  • Gene Expression Regulation
  • Healthy Volunteers
  • Histones / metabolism
  • Humans
  • Italy
  • Male
  • Nuclear Proteins / metabolism*
  • Oxidative Stress*
  • Protamines / metabolism
  • Protein Binding
  • Spermatozoa / chemistry*
  • Spermatozoa / metabolism
  • Young Adult

Substances

  • Histones
  • Nuclear Proteins
  • Protamines
  • sperm basic nuclear proteins
  • Copper
  • DNA
  • Arginine