Biochem Biophys Res Commun. 2006 Oct 20;349(2):759-68. Epub 2006
Aug 28.Dividing roles of prion protein in
staurosporin-mediated apoptosis.
Zhang Y, Qin K, Wang J, Hung T,
Zhao RY.
Institute of Basic Medical Sciences, Peking Union Medical
College, Chinese Academy of Medical Sciences, Beijing 100005,
People's Republic of China.
Prion protein (PrPC) is a normal cellular glycoprotein that
is expressed in almost all tissues including the central nervous
system. Much attention has been focused on this protein because
conversion of the normal PrPC to the diseased form (PrPSc) plays
an essential role in transmissible spongiform encephalopathies
such as mad cow disease and Creutzfeldt-Jakob disease. In spite
of the extensive effort, the normal physiological function of
PrPC remains elusive. Emerging evidence suggestaurosporin
that PrPC plays a protective role against cellular stresses
including apoptosis induced by various pro-apoptotic agents such
as Bax and staurosporin, however, other reports showed
overexpression of PrPC enhances staurosporin -mediated
apoptosis. In this study, we took a different approach by
depleting endogenous PrPC using specific interfering RNA
technique and compared the depleting and overproducing effects
of PrPC on staurosporin -induced apoptosis in neuro-2a (N2a)
cells. We demonstrate here that down-regulation of PrPC
sensitizes N2a cells to staurosporin -induced
cytotoxicity and apoptosis. The enhanced apoptosis induced by
staurosporin was shown by increased DNA
fragmentation, immunoreactivity of Bax, and caspase-3 cleavage.
We also showed that overproduction of PrPC had little or no
effect on staurosporin -mediated DNA fragmentation in N2a
cells but it augments staurosporin -mediated apoptosis in
HEK293 cells, suggesting a cell line-specific effect. In
addition, the inhibitory effect of PrPC on staurosporin
-mediated cellular stress appears to be modulated in part
through induction of cell cycle G2 accumulation. Together, our
data suggest that physiological level of endogenous PrPC plays a
protective role against staurosporin -mediated cellular
stress. Loss of this protection could render cells more prone to
cellular insults such as staurosporin .
PMID: 16950206 |
