Molecular and Cellular Biochemistry

, Volume 298, Issue 1–2, pp 139–150 | Cite as

Inhibition of CDC2/Cyclin B1 in response to selenium-induced oxidative stress during spermatogenesis: potential role of Cdc25c and p21

Original Paper
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Abstract

Various cell cycle regulators control and coordinate the process of cell cycle. Because of the crucial involvement of CDC2, Cyclin B1, Cdc25c, and p21 in cell cycle regulation, the present study was aimed to investigate the possibility that selenium (Se)-induced oxidative stress mediated alterations in Cdc25c and p21 may cause modulations in the CDC2/Cyclin B1 complex responsible for G2/M phase checkpoint during meiosis I of spermatogenesis. To create different Se status-deficient, adequate and excess Se, male Balb/c mice were fed yeast based Se deficient diet (group I) and deficient diet supplemented with Se as sodium selenite at 0.2 and 1 ppm Se (group II and III) for a period of 8 weeks. After completion of the diet feeding schedule, a significant decrease in the Se and glutathione peroxidase levels were observed in the Se deficient group (I), whereas Se excess group (III) demonstrated an increase in Se levels. Increased levels of lipid peroxidation (LPO) were seen in both group I and group III when compared to group II, thus indicating oxidative stressed conditions. The mRNA and protein expression of CDC2, Cyclin B1, and Cdc25c were found to be significantly decreased in groups I and III. However, the expression of p21, a kinase inhibitor, was found to be elevated in Se deficient and Se excess fed groups. A statistically significant decrease in the CDC2 kinase activity was also seen in the Se deficient and excess groups. These findings suggest that under the influence of Se-induced oxidative stress, the down regulation of CDC2/Cyclin B1 complex is mediated through changes in Cdc25c and p21 leading to the cell cycle arrest and thus providing new dimensions to the molecular mechanisms underlying male infertility.

Keywords

Selenium Oxidative stress CDC2 Cyclin B1 Cdc25c p21 
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Notes

Acknowledgement

Authors acknowledge the financial support provided by Indian council of medical research (ICMR), Government of India, New Delhi (India).

References

  1. 1.
    Pines J (1994) The cell cycle kinases Semin. Cancer Biol 5:305–313Google Scholar
  2. 2.
    Taylor WR, Stark GR (2001) Regulation of G2/M transition by p53. Oncogene 20:1803–1815PubMedCrossRefGoogle Scholar
  3. 3.
    Morgan DO (1997) Cyclin dependent kinases: engines clocks and microprocessors. Annu Rev Cell Dev Biol 13:261–291Google Scholar
  4. 4.
    Solomon MJ (1994) The Function(s) of CDK the p34cdc2-activating kinase. Trends Biochem Sci 19:498–500CrossRefGoogle Scholar
  5. 5.
    Nilsson I, Hoffmann I (2000) Cell cycle regulation by the CDC25 phosphatase family. Prog Cell Cycle Res 4:107–114PubMedGoogle Scholar
  6. 6.
    Sanchez Y, Wong C, Thoma RS, Richman R, Wu Z, Piwnica-Worms H, Elledge SJ (1997) Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science 277:1497–1501PubMedCrossRefGoogle Scholar
  7. 7.
    Savitsky PA, Finkel T (2002) Redox regulation of Cdc 25c. J Biol Chem 277:20535–20540PubMedCrossRefGoogle Scholar
  8. 8.
    Baus F, Gire V, fisher D, Piette J, Dulic V. (2003) Permanent cell cycle exit in G2 phase after DNA damage in normal human fibroblasts. EMBO J 22:3992–4002PubMedCrossRefGoogle Scholar
  9. 9.
    Charrier-Savournin FB, Chateau MT, Gire V, Sedivy J, fisher D, Piette J, Dulic V (2004) P21-mediated nuclear retention of cyclin B1-CDK1 in response to genotoxic stress. Mol Biol Cell 15:3965–3976PubMedCrossRefGoogle Scholar
  10. 10.
    West A, Priante G, Lahdetie J (2002) Stage-specific expression of Gadd45 induced by X-irradiation in rat spermatogenesis. Int J Radiat Biol 78(1):29–39PubMedCrossRefGoogle Scholar
  11. 11.
    Schwartz D, Goldfinger N, Kam Z, Rotter V (1999) P53 controls low DNA damage-dependent premeiotic checkpoint and facilitates DNA repair during spermatogenesis. Cell Growth Differ 10:665–675PubMedGoogle Scholar
  12. 12.
    Agarwal A, Said TM (2003) Role of sperm chromatin abnormalities DNA damage in male infertility. Human Reprod Update 9:331–345CrossRefGoogle Scholar
  13. 13.
    Shackelford RE, Kaufmann WK, Paules RS (2000) Oxidative stress and cell cycle checkpoint function. Free Radical Biol Med 28(9):1387–1404CrossRefGoogle Scholar
  14. 14.
    Sundaram N, Pahwa AK, Ard MD, Lin N, Perkins E, Bowles AP Jr. (2000) Selenium causes growth inhibition and apoptosis in human brain tumor cell lines. J Neurooncol 46:125–133PubMedCrossRefGoogle Scholar
  15. 15.
    Stewart MS, Spallholz JE, Neidner KH, Pence BC (1999) Selenium compounds have disparate abilities to impose oxidative stress and induce apoptosis. Free Rad Biol Med 26:42–48PubMedCrossRefGoogle Scholar
  16. 16.
    Kaur P, Bansal MP (2003) Effect of oxidative stress on the spermatogenic process and hsp70 expressions in mice testes. Ind J Biochem Biophys 40:246–251Google Scholar
  17. 17.
    Rao L, Puschner B, Prolla TA (2001) Gene expression profiling of low selenium status in the mouse intestine: transcriptional activation of genes linked to DNA damage, cell cycle control and oxidative stress. J Nutrition 131:3175–3181Google Scholar
  18. 18.
    Ip C, Thompson HJ, Ganther HE (2000) Selenium modulation of cell proliferation and cell cycle biomarkers in normal and premalignant cells of the rat mammary gland. Cancer Epidemiol Biomark Prev 9:49–54Google Scholar
  19. 19.
    Burk RF (1987) Production of selenium deficiency in the rat. Methods Enzymol 143:307–313PubMedCrossRefGoogle Scholar
  20. 20.
    Hasunuma R, Ogawi T, Kawaniska Y (1986) Fourimetric determination of selenium in nanogram amounts in biological materials using 2, 3-diaminonapthalene. Anal Biochem 126:242–245CrossRefGoogle Scholar
  21. 21.
    Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–168PubMedGoogle Scholar
  22. 22.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  23. 23.
    Wills ED (1966) Mechanisms of lipid peroxide formation in animal tissues. Biochem J 99(3):667–676PubMedGoogle Scholar
  24. 24.
    Driver AS, Rao P, Kodavanti S, Mundy WR (2000) Age-related changes in the reactive oxygen species production in rat brain homogenates. Neurotoxicol Teratol 22:175–181PubMedCrossRefGoogle Scholar
  25. 25.
    Takahashi M, Seki N, Ozaki T, Kato M, Kuno T, Nakagawa T, Watanabe K et al (2002) Identification of the p33ING1-regulated genes that include Cyclin b1 and proto-oncogene DEK by using cDNA microarray in a mouse mammary epithelial cell line NMuMG. Cancer Res 62:2203–2209PubMedGoogle Scholar
  26. 26.
    Jiao X, Trifillis P, Kiledjan M (2002) Identification of target messenger RNA substrates for the murine deleted in azoospermia-like RNA-binding protein. Biol Reprod 66:475–485PubMedCrossRefGoogle Scholar
  27. 27.
    Yamada K, Takane-Gyotoku N, Yuan X, Ichikawa F, Inada C, Nonaka K (1996) Mouse islet cell lysis mediated by interleukin-1-induced Fas. Diabetologia 39:1306–1312PubMedCrossRefGoogle Scholar
  28. 28.
    Zhu D, Dix DJ, Eddy EM (1997) HSP70-2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes. Development 124:3007–3014PubMedGoogle Scholar
  29. 29.
    Olson EG, Winfrey VP, Hill KE, Burk RF (2004) Sequential development of flagellar defects in spermatids and epididymal spermatozoa of selenium-deficient rats. Reproduction 127:335–342PubMedCrossRefGoogle Scholar
  30. 30.
    Kaur P, Bansal MP (2005) Effect of selenium-induced oxidative stress on the cell kinetics in testis and reproductive ability of male mice. Nutrition 21:351–357PubMedCrossRefGoogle Scholar
  31. 31.
    Spallholz JE (2001) Selenium and the prevention of cancer. Part II: mechanism for the carcinostatic activity of Se compounds. Bull Se-Te Develop Assoc: 1–12Google Scholar
  32. 32.
    Nayernia K, Diaconu M, Aunuller G, Wennemuth G, Schwandt I, Kleene K, Kuehn H, Engel W (2004) Phospholipid hydroperoxide glutathione peroxidase: expression pattern during testicular development in mouse and evolutionary conservation in spermatozoa. Mol Reprod Develop 67:458–464CrossRefGoogle Scholar
  33. 33.
    Lei XG, Evenson JK, Thompson KM, Sunde RA (1995) Glutathione peroxidase and phospholipids hydroperoxide glutathione peroxidase are differentially regulated in rats by dietary selenium. J Nutr 125:1438–1446PubMedGoogle Scholar
  34. 34.
    Muller AS, Pallauf J (2002) Down regulation of GPx1mRNA and the loss of GPx1activity causes cellular damage in the liver of selenium deficient rabbits. J Anim Physiol Anim Nutr 86:273–287CrossRefGoogle Scholar
  35. 35.
    Shen HM, Yang DM, Ding WX, Liu J, Ong DN (2001) Superoxide radical-initiated apoptotic signaling pathways in selenite-treated HEPR2 cells: Mitochondria serve as the main target. Free Radical Biol Med 30:9–21CrossRefGoogle Scholar
  36. 36.
    Aitken RJ, Clarkson JS (1987) Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J Reprod Fertil 81:459–469PubMedCrossRefGoogle Scholar
  37. 37.
    Alvarez JG, Touchstone JC, Blasco L, Storey BT (1987) Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa. Superoxide dismutase as a major enzyme protectant against oxygen toxicity. J Androl 8:338–348PubMedGoogle Scholar
  38. 38.
    Saito Y, Yoshida Y, Akazawa T, Takahashi K, Niki E (2003) Cell death caused by Selenium deficiency and protective effect of antioxidants. J Biol Chem 278(41):39428–39434PubMedCrossRefGoogle Scholar
  39. 39.
    Saleh RL, Agarwal A (2002) Oxidative stress and male infertility: from research bench to clinical practice. J Androl 23:737–752PubMedGoogle Scholar
  40. 40.
    Saleh RA, Agarwal A, Sharma RK, Nelson DR, Thomas AJ (2002) Effect of cigarette smoking levels of seminal oxidative stress in infertile men; a perspective study. Fertil Steril 78:491–499PubMedCrossRefGoogle Scholar
  41. 41.
    Ongkeko W, Ferguson JP, Harris AL, Norbury C (1995) Inactivation of Cdc2 increases the level of apoptosis induced by DNA damage. J Cell Sci 108:2897–2904PubMedGoogle Scholar
  42. 42.
    Shi L, Nishioka WK, Th’ng J, Bradbury EM, Litchfield DW, Greenberg AH (1994) Premature p34cdc2 activation required for apoptosis. Science 263:1143–1145PubMedCrossRefGoogle Scholar
  43. 43.
    Zeng H (2002) Selenite and selenomethionine promote HL-60 cell cycle progression. J Nutr 132:674–679PubMedGoogle Scholar
  44. 44.
    Zeng H (2001) Arsenic suppresses necrosis induced by selenite in human leukemia HL-60 cells. Biol Trace Elem Res 83:1–15PubMedCrossRefGoogle Scholar
  45. 45.
    Maity A, Mckenna WG, Muschel RJ (1995) Evidence for post-transcriptional regulation of cyclin B1 mRNA in the cell cycle and following irradiation in HeLa cells. EMBO J 14:603–609PubMedGoogle Scholar
  46. 46.
    Innocente SA, Abrahamson JL, Cogswell JP, Lee JM (1999) P53 regulates a G2 checkpoint through cyclin B1. Proc Natl Acad Sci USA 96:2147–2152PubMedCrossRefGoogle Scholar
  47. 47.
    Ji C, Rouzer CA, Marnett LJ, Pietenpol JA (1998) Induction of cell cycle arrest by the endogeneous product of lipid peroxidation, malondialdehyde. Carcinogenesis 19(7):1275–1283PubMedCrossRefGoogle Scholar
  48. 48.
    Chigbrow M, Nelson M (2001) Inhibition of mitotic cyclin B and cdc2 kinase activity by selenomethionine in synchronized colon cancer cells. Anti-cancer Drugs 12:43–50PubMedCrossRefGoogle Scholar
  49. 49.
    Blasina A, Price BD, Turenne GA, McGowan CH (1999) Caffeine inhibits the checkpoint kinase ATM. Curr Biol 9:1135–1138PubMedCrossRefGoogle Scholar
  50. 50.
    Xiao D, Herman-Antosiewicz A, Antosiewicz J, Xiao H, Brisson M, Lazo JS, Singh SV (2005) Diallyl trisulfide-induced G2-M phase cell cycle arrest in human prostate canacer cells is caused by reactive oxygen species-dependent destruction and hyperphosphorylation of Cdc25c. Oncogene 24:6256–6268Google Scholar
  51. 51.
    Russo T, Zamrano N, Esposito F, Ammendola R, Cimino F, Fiscella M, Jackman J, O’Connor PM, Anderson CW, Apella F (1995) A p53-independent Pathway for Activation of WAF1/CIP1 Expression Following Oxidative Stress. J Biol Chem 270:29386–29391PubMedCrossRefGoogle Scholar
  52. 52.
    Qiu X, Forman HJ, Schonthal AH, Cadenas E (1996) Induction of p21 Mediated by Reactive Oxygen Species Formed during the Metabolism of Aziridinylbenzoquinones by HCT116 Cells. J Biol Chem 271:31915–31921PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  1. 1.Department of BiophysicsPanjab UniversityChandigarhIndia

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