Omega-Class Glutathione Transferases Protect DNA from Oxidative Stress in Pathogenic Helminth Reproductive Cells

Area of Science:

• Parasitology
• Molecular Biology
• Biochemistry

Background:

• Pathogenic helminths survive host immune responses by preserving reproductive function.
• Antioxidant enzymes are proposed to protect against DNA degradation, but evidence is limited.
• Omega-class glutathione transferases (GSTOs) are key in cellular defense mechanisms.

Purpose of the Study:

• To investigate the role of GSTOs in protecting the reproductive cell DNA of *Clonorchis sinensis* from oxidative stress.
• To elucidate the mechanisms by which CsGSTOs regulate redox balance and prevent DNA damage.

Main Methods:

• Assessed *Clonorchis sinensis* GSTO (CsGSTO) activity under varying glutathione (GSH/GSSG) and NADPH/NADP+ ratios.
• Utilized gliotoxin to disrupt CsGSTO function in living parasites and observed effects on protein glutathionylation and DNA integrity.
• Investigated nuclear translocation of CsGSTOs and their modification by glutathionylation using specific antibodies.

Main Results:

• CsGSTOs regulated reactive oxygen species production by modulating GSH/GSSG and NADPH/NADP+ ratios.
• CsGSTO1 and CsGSTO2 catalyzed deglutathionylation under low stress and glutathionylation under high stress.
• Disruption of CsGSTOs led to DNA degradation, indicating their critical role in DNA protection via glutathionylation.

Conclusions:

• CsGSTOs are essential for maintaining parasite viability by protecting reproductive cell DNA from oxidative damage.
• The glutathione system, regulated by CsGSTOs, plays a vital role in preventing DNA degradation in *C. sinensis*.
• CsGSTO-mediated glutathionylation serves as a protective mechanism against DNA damage in helminths.