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Low concentrations of hydrogen peroxide activate the antioxidant defense system in human sperm cells

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Abstract

The effect of low concentrations of hydrogen peroxide (10–100 µM) on sperm motility and on the activity of the sperm enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDS) was investigated. Incubation of semen samples with 10 and 100 µM hydrogen peroxide increased the content of spermatozoa with progressive motility by 20 and 18%, respectively, and enhanced the activity of GAPDS in the sperm cells by 27 and 20% compared to a semen sample incubated without additions. It was also found that incubation with 10 µM hydrogen peroxide increased the content of reduced glutathione (GSH) in sperm cells by 50% on average compared to that in the control samples. It is supposed that low concentrations of hydrogen peroxide activate the pentose phosphate pathway, resulting in NADPH synthesis and the reduction of the oxidized glutathione by glutathione reductase yielding GSH. The formed GSH reduces the oxidized cysteine residues of the GAPDS active site, increasing the activity of the enzyme, which in turn enhances the content of sperm cells with progressive motility. Thus, the increase in motile spermatozoa in the presence of low concentrations of hydrogen peroxide can serve as an indicator of normal functioning of the antioxidant defense system in sperm cells.

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Abbreviations

ATM:

serine/threonine protein kinase

dN-GAPDS:

recombinant GAPDS without N-terminal domain

GAPDS:

sperm-specific glyceraldehyde-3-phosphate dehydrogenase

G6PD:

glucose-6-phosphate dehydrogenase

PPP:

pentose phosphate pathway

ROS:

reactive oxygen species

References

  1. Mazzilli, F., Rossi, T., Marchesini, M., Ronconi, C., and Dondero, F. (1994) Superoxide anion in human semen related to seminal parameters and clinical aspects, Fertil. Steril., 62, 862–868.

    CAS  PubMed  Google Scholar 

  2. Sharma, R. K., and Agarwal, A. (1996) Role of reactive oxygen species in male infertility, Urology, 48, 835–850.

    Article  CAS  PubMed  Google Scholar 

  3. Aitken, R. J., and Sawyer, D. (2003) The human spermatozoon — not waving but drowning, Adv. Exp. Med. Biol., 518, 85–98.

    Article  PubMed  Google Scholar 

  4. Agarwal, A., Saleh, R. A., and Bedaiwy, M. A. (2003) Role of reactive oxygen species in the pathophysiology of human reproduction, Fertil. Steril., 79, 829–843.

    Article  PubMed  Google Scholar 

  5. Elkina, Yu. L., Atroshchenko, M. M., Bragina, E. E., Muronetz, V. I., and Schmalhausen, E. V. (2011) Oxidation of glyceraldehyde-3-phosphate dehydrogenase decreases sperm motility, Biochemistry (Moscow), 76, 268–272.

    Article  CAS  Google Scholar 

  6. Westhoff, W., and Kamp, G. (1997) Glyceraldehyde 3phosphate dehydrogenase is bound to the fibrous sheath of mammalian spermatozoa, J. Cell Sci., 110, 1821–1829.

    CAS  PubMed  Google Scholar 

  7. Welch, J. E., Brown, P. L., O’ Brien, D. A., Magyar, P. L., Bunch, D. O., Mori, C., and Eddy, E. M. (2000) Human glyceraldehyde 3-phosphate dehydrogenase-2 gene is expressed specifically in spermatogenic cells, J. Androl., 21, 328–338.

    CAS  PubMed  Google Scholar 

  8. Tanii, I., Yagura, T., Inagaki, N., and Yoshinaga, K. (2007) Preferential localization of rat GAPDS on the ribs of fibrous sheath of sperm flagellum and its expression during flagellar formation, Acta Histochem. Cytochem., 40, 19–26.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Miki, K., Ou, W., Goulding, E., Willis, W. D., Bunch, D. O., Stadler, L. F., Perreault, S. D., Eddy, E. M., and O’Brien, D. A. (2004) Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility, Proc. Natl. Acad. Sci. USA, 101, 16501–16506.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Little, C., and O’Brien, P. J. (1969) Mechanism of peroxide-inactivation of the sulfhydryl enzyme glyceraldehyde3-phosphate dehydrogenase, Eur. J. Biochem., 10, 533–538.

    Article  CAS  PubMed  Google Scholar 

  11. Schmalhausen, E. V., Nagradova, N. K., Boschi-Muller, S., Branlant, G., and Muronetz, V. I. (1999) Mildly oxidized GAPDH: the coupling of the dehydrogenase and acyl phosphatase activities, FEBS Lett., 452, 219–222.

    Article  CAS  PubMed  Google Scholar 

  12. Elkina, Yu. L., Kuravsky, M. L., El’darov, M. A., Stogov, S. V., Muronetz, V. I., and Schmalhausen, E. V. (2010) Recombinant human sperm-specific glyceraldehyde-3phosphate dehydrogenase: structural basis for enhanced stability, Biochim. Biophys. Acta, 1804, 2207–2212.

    Article  CAS  PubMed  Google Scholar 

  13. Aitken, R. J., Paterson, M., Fisher, H., Buckingham, D. W., and van Duin, M. (1995) Redox regulation of tyrosine phosphorylation in human spermatozoa and its role in the control of human sperm function, J. Cell Sci., 108, 2017–2025.

    CAS  PubMed  Google Scholar 

  14. Rivlin, J., Mendel, J., Rubinstein, S., Etkovitz, N., and Breitbart, H. (2004) Role of hydrogen peroxide in sperm capacitation and acrosome reaction, Biol. Reprod., 70, 518–522.

    Article  CAS  PubMed  Google Scholar 

  15. Shahar, S., Wiser, A., Ickowicz, D., Lubart, R., Shulman, A., and Breitbart, H. (2011) Light-mediated activation reveals a key role for protein kinase A and sarcoma protein kinase in the development of sperm hyper-activated motility, Hum. Reprod., 26, 2274–2282.

    Article  CAS  PubMed  Google Scholar 

  16. Dan’shina, P. V., Schmalhausen, E. V., Avetisyan, A. V., and Muronetz, V. I. (2001) Mildly oxidized glyceraldehyde-3-phosphate dehydrogenase as a possible regulator of glycolysis, IUBMB Life, 51, 309–314.

    Article  Google Scholar 

  17. Bradford, M. M. (1976) A rapid and sensitive method of quantitation of microgram quantities of protein utilizing the principle of protein-due binding, Anal. Biochem., 72, 248–254.

    Article  CAS  PubMed  Google Scholar 

  18. Shchutskaya, Y. Y., Elkina, Y. L., Kuravsky, M. L., Bragina, E. E., and Schmalhausen, E. V. (2008) Investigation of glyceraldehyde-3-phosphate dehydrogenase from human sperms, Biochemistry (Moscow), 73, 185–191.

    Article  CAS  Google Scholar 

  19. Williams, A. C., and Ford, W. C. L. (2004) Functional significance of the pentose phosphate pathway and glutathione reductase in the antioxidant defenses of human sperm, Biol. Reprod., 71, 1309–1316.

    Article  CAS  PubMed  Google Scholar 

  20. Stanton, R. S. (2012) Glucose-6-phosphate dehydrogenase, NADPH, and cell survival, IUBMB Life, 64, 362–369.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Rotman, G., and Shiloh, Y. (1997) The ATM gene and protein: possible roles in genome surveillance, checkpoint controls and cellular defense against oxidative stress, Cancer Surv., 29, 285–304.

    CAS  PubMed  Google Scholar 

  22. Rotman, G., and Shiloh, Y. (1997) Ataxia-telangiectasia: is ATM a sensor of oxidative damage and stress? BioEssays, 19, 911–917.

    Article  CAS  PubMed  Google Scholar 

  23. Shiloh, Y. (2006) The ATM-mediated DNA-damage response: taking shape, Trends Biochem. Sci., 31, 402–410.

    Article  CAS  PubMed  Google Scholar 

  24. Reichenbach, J., Schubert, R., Schindler, D., Muller, K., Bohles, H., and Zielen, S. (2002) Elevated oxidative stress in patients with ataxia telangiectasia, Antioxid. Redox Signal., 4, 465–469.

    Article  CAS  PubMed  Google Scholar 

  25. Guo, Z., Kozlov, S., Lavin, M. F., Person, M. D., and Paull, T. T. (2010) ATM activation by oxidative stress, Science, 330, 517–521.

    Article  CAS  PubMed  Google Scholar 

  26. Preville, X., Salvemini, F., Giraud, S., Chaufour, S., Paul, C., Stepien, G., Ursini, M. V., and Arrigo, A. P. (1999) Mammalian small stress proteins protect against oxidative stress through their ability to increase glucose-6-phosphate dehydrogenase activity and by maintaining optimal cellular detoxifying machinery, Exp. Cell Res., 247, 61–78.

    Article  CAS  PubMed  Google Scholar 

  27. Cosentino, C., Grieco, D., and Costanzo, V. (2011) ATM activates the pentose phosphate pathway promoting antioxidant defense and DNA repair, EMBO J., 30, 546–555.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Stanton, R. C., Seifter, J. L., Boxer, D. C., Zimmerman, E., and Cantley, L. C. (1991) Rapid release of bound glucose-6-phosphate dehydrogenase by growth factors. Correlation with increased enzymatic activity, J. Biol. Chem., 266, 12442–12448.

    CAS  PubMed  Google Scholar 

  29. Swezey, R. R., and Epel, D. (1986) Regulation of glucose6-phosphate dehydrogenase activity in sea urchin eggs by reversible association with cell structural elements, J. Cell Biol., 103, 1509–1515.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to E. V. Schmalhausen.

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Published in Russian in Biokhimiya, 2015, Vol. 80, No. 9, pp. 1431–1439.

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Evdokimov, V.V., Barinova, K.V., Turovetskii, V.B. et al. Low concentrations of hydrogen peroxide activate the antioxidant defense system in human sperm cells. Biochemistry Moscow 80, 1178–1185 (2015). https://doi.org/10.1134/S0006297915090084

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  • DOI: https://doi.org/10.1134/S0006297915090084

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