Selenite activates the ATM kinase-dependent DNA repair pathway in human osteosarcoma cells with mitochondrial

Marta Wojewoda1, Jarosław Walczak1, Jerzy Duszyński1

  • 1Laboratory of Bioenergetics and Biomembranes, Department of Biochemistry, Nencki Institute of Experimental Biology, 3 Pasteur St, 02-993 Warsaw, Poland.

Insights

Selenium (selenite) may protect against DNA damage in certain cells. This study found selenite activated DNA repair mechanisms in cells with mitochondrial dysfunction, suggesting a protective role.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Mitochondrial dysfunction and reactive oxygen species (ROS) contribute to human diseases.
  • Previous studies showed increased ROS in NARP cybrids, with selenite reducing ROS levels.

Purpose of the Study:

  • To investigate the effects of selenite on oxidative and nitrosative damage in cells with mitochondrial dysfunction.
  • To explore selenite's impact on DNA damage and repair pathways.

Main Methods:

  • Comparison of NARP cybrids and Rho0 cells (lacking mitochondrial DNA) with control WT cells.
  • Assessment of oxidative/nitrosative damage to lipids, proteins, and DNA.
  • Measurement of histone γH2AX levels and ATM kinase activity.

Main Results:

  • No increased oxidative/nitrosative damage to lipids or proteins was observed in NARP or Rho0 cells.
  • Enhanced formation of DNA double-strand breaks, indicated by histone γH2AX, was found in NARP cybrids and Rho0 cells.
  • Selenite increased ATM kinase activity in NARP and Rho0 cells, but without a corresponding rise in histone γH2AX levels.

Conclusions:

  • Selenite's activation of ATM kinase in NARP and Rho0 cells is not linked to increased DNA damage.
  • Selenite may exert protective effects by activating ATM kinase-dependent DNA repair pathways in cells with mitochondrial dysfunction.

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