Does Ataxia Telangiectasia Mutated (ATM) protect testicular and germ cell DNA integrity by regulating the redox status?
A balanced redox homeostasis in the testis is essential for genetic integrity of sperm. Reactive oxygen species can disturb this balance by oxidation of glutathione, which is regenerated using NADPH, formed by glucose-6-phosphate dehydrogenase (G6PDH). G6PDH is regulated by the Ataxia Telangiectasia Mutated (Atm) protein. Therefore, we studied the redox status and DNA damage in testes and sperm of mice that carried a deletion in Atm. The redox status in heterozygote mice, reflected by glutathione levels and antioxidant capacity, was lower than in wild type mice, and in homozygotes the redox status was even lower. The redox status correlated with oxidative DNA damage that was highest in mice that carried Atm deletions. Surprisingly, G6PDH activity was highest in homozygotes carrying the deletion. These data indicate that defective Atm reduces the redox homeostasis of the testis and genetic integrity of sperm by regulating glutathione levels independently from G6PDH activity.
Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, The Netherlands. Electronic address: r.godschalk@maastrichtuniversity.nl.
Roger W L
RW
Godschalk
Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, The Netherlands.
Kimberly
K
Vanhees
Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, The Netherlands.
Lou
L
Maas
Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, The Netherlands.
Marie-Jose
MJ
Drittij
Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, The Netherlands.
Daniëlle
D
Pachen
Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, The Netherlands.
Sahar van Waalwijk
Sv
van Doorn-Khosrovani
Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, The Netherlands.
Frederik J
FJ
van Schooten
Department of Pharmacology & Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, The Netherlands.
Guido R M M
GR
Haenen
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics; D020552:Comet Assay; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005838:Genotype; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D008297:Male; D051379:Mice; D009154:Mutation; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*
D000080242:8-Hydroxy-2'-Deoxyguanosine; D005954:Glucosephosphate Dehydrogenase; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D003849:Deoxyguanosine; D005978:Glutathione
Ataxia Telangiectasia Mutated; DNA damage; Glucose-6-phosphate dehydrogenase; Glutathione; Oxidative stress; Testis