|
|
Prepublished online as a Blood First Edition Paper on May 24, 2002; DOI 10.1182/blood-2001-11-0073.
 Previous Article | Table of Contents | Next Article 
Blood, 1 September 2002, Vol. 100, No. 5, pp. 1802-1809
NEOPLASIA
Modulation of the activity of calcium-activated neutral proteases
(calpains) in chronic lymphocytic leukemia (B-CLL) cells
Jacek M. Witkowski,
Emilia Zmuda-Trzebiatowska,
Jakub M. Swiercz,
Miroslawa Cichorek,
Hanna Ciepluch,
Krzysztof Lewandowski,
Ewa Bryl, and
Andrzej Hellmann
From the Department of Pathophysiology, Department of
Embryology, Department of Hematology, and Department of
Immunopathology, Medical University of Gdansk, Poland.
Decreased susceptibility to apoptosis and impaired proliferative
control are thought to be responsible for prolonged life span and
accumulation of chronic lymphocytic leukemia (B-CLL) cells. The
activity of calpains (calcium-dependent, neutral proteases, active in
the cells responding to signals inducing a rise of cytoplasmic Ca++) is involved in the regulation of apoptosis of some
cell types by interaction with caspase-3. This work verifies the
hypothesis of the abnormal activity of calpains and its role in reduced
apoptosis of the B-CLL cells. Casein zymography, reverse
transcriptase-polymerase chain reaction, and Western blotting were
used for identification and quantification of the activity and
expression of calpains in B-CLL cells and purified normal B
lymphocytes. The activity and expression of µ-calpain (requiring
micromolar Ca++ for activation) are significantly higher in
the leukemic than in nonmalignant cells. Contrarily, the activity and
expression of m-calpain (requiring millimolar Ca++) as
well as the expression of calpastatin (an endogenous inhibitor of
calpains) are unchanged or reduced in the B-CLL lymphocytes. Correspondingly, the activity of caspase-3 is many times lower in the
B-CLL cells than in normal B lymphocytes. Inhibition of overexpressed
µ-calpain in living B-CLL cells in vitro results in doubling of the
proportion of the cells undergoing spontaneous apoptosis. This
observation suggests a possible role for calpains in longer survival of
the B-CLL cells and may open new therapeutic possibilities.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S.-R. A. Hussain, D. M. Lucas, A. J. Johnson, T. S. Lin, A. P. Bakaletz, V. X. Dang, S. Viatchenko-Karpinski, A. S. Ruppert, J. C. Byrd, P. Kuppusamy, et al.
Flavopiridol causes early mitochondrial damage in chronic lymphocytic leukemia cells with impaired oxygen consumption and mobilization of intracellular calcium
Blood,
March 15, 2008;
111(6):
3190 - 3199.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Nuzzi, M. A. Senetar, and A. Huttenlocher
Asymmetric Localization of Calpain 2 during Neutrophil Chemotaxis
Mol. Biol. Cell,
March 1, 2007;
18(3):
795 - 805.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Xu and X. Deng
Suppression of Cancer Cell Migration and Invasion by Protein Phosphatase 2A through Dephosphorylation of {micro}- and m-Calpains
J. Biol. Chem.,
November 17, 2006;
281(46):
35567 - 35575.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Fettucciari, I. Fetriconi, R. Mannucci, I. Nicoletti, A. Bartoli, S. Coaccioli, and P. Marconi
Group B streptococcus induces macrophage apoptosis by calpain activation.
J. Immunol.,
June 15, 2006;
176(12):
7542 - 7556.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Xu and X. Deng
Protein Kinase C{iota} Promotes Nicotine-induced Migration and Invasion of Cancer Cells via Phosphorylation of {micro}- and m-Calpains
J. Biol. Chem.,
February 17, 2006;
281(7):
4457 - 4466.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Lakshmikuttyamma, P. Selvakumar, R. Kanthan, S. C. Kanthan, and R. K. Sharma
Overexpression of m-Calpain in Human Colorectal Adenocarcinomas
Cancer Epidemiol. Biomarkers Prev.,
October 1, 2004;
13(10):
1604 - 1609.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Wada, S. H. Schurman, G. J. Jagadeesh, E. K. Garabedian, D. L. Nelson, and F. Candotti
Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome family
Blood,
September 1, 2004;
104(5):
1270 - 1272.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. W. Neumar, Y. A. Xu, H. Gada, R. P. Guttmann, and R. Siman
Cross-talk between Calpain and Caspase Proteolytic Systems During Neuronal Apoptosis
J. Biol. Chem.,
April 11, 2003;
278(16):
14162 - 14167.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
