ORIGINAL PAPER
Inhibition of CDC2/Cyclin B1 in response to selenium-induced
oxidative stress during spermatogenesis: potential role of Cdc25c
and p21
Naveen Kaushal Æ M. P. Bansal
Received: 15 July 2006 / Accepted: 25 October 2006 / Published online: 12 December 2006
Ó
Springer Science+Business Media B.V. 2006
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 ex-
cess 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 defi-
cient and Se excess fed groups. A statistically signifi-
cant 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 pro-
viding new dimensions to the molecular mechanisms
underlying male infertility.
Keywords Selenium Á Oxidative stress Á CDC2 Á
Cyclin B1 Á Cdc25c Á p21
Introduction
The control of the progression of the cell cycle is vital
to the terminal differentiation, growth, and develop-
ment of any cell [1]. The proper execution of cell cycle
events is ensured through regulation at the cell cycle
checkpoints. Cdc2/cyclin B1 complex called maturation
promotion factor (MPF) synchronizes the activity of
one of these critical checkpoints known as G2/M phase
transition of the cell cycle [2]. The activity of these
kinases is further coordinated by CDK-inhibitory
proteins called CDKIs [3] and the mechanisms
involving phosphorylation and dephosphorylation of
residues on the CDK subunit [4]. Cdc25 and p21 con-
stitute two of the most important cell cycle regulators
that affect the cell cycle progression by modulating the
cell cycle checkpoints through cyclin-dependent kin-
ases.
Cdc25c is a member of protein phosphatase family,
which affects G2/M phase transition of cell cycle
through dephosphorylation and hence activation of
Cdc2 [5]. In response to oxidative stress, the protein
Cdc25c gets phosphorylated and this prevents the
activation of Cdc2/Cyclin B1 complex, thereby leading
to the arrest of G2/M transition [6]. Conversely, the
N. Kaushal Á M. P. Bansal (&)
Department of Biophysics, Panjab University,
Chandigarh 160014, India
e-mail: mpbansal@pu.ac.in
123
Mol Cell Biochem (2007) 298:139–150
DOI 10.1007/s11010-006-9360-y