title: Inhibition of CDC2/Cyclin B1 in response to selenium-induced oxidative stress during spermatogenesis: potential role of Cdc25c and p21.
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.
authors.affiliation: Department of Biophysics, Panjab University, Chandigarh, 160014, India.
authors.forename: Naveen
authors.initials: N
authors.lastname: Kaushal
authors.forename: M P
authors.initials: MP
authors.lastname: Bansal
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D019926:Cyclin B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D005786:Gene Expression Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects*; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012643:Selenium / Q000378:metabolism / Q000494:pharmacology*; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000201:enzymology; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism*
chemical_list: C534700:Ccnb1 protein, mouse; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D011494:Protein Kinases; C102333:histone H1 kinase; D016203:CDC2 Protein Kinase; C517010:Cdc25c protein, mouse; D020687:cdc25 Phosphatases; D012643:Selenium