|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 95 No. 4 (February 15), 2000:
pp. 1427-1434
Apoptosis of leukemic cells accompanies reduction in intracellular
pH after targeted inhibition of the Na+/H+
exchanger
Ivan N. Rich,
Diana Worthington-White,
Oliver A. Garden, and
Philip Musk
From the Division of Transplantation Medicine, South Carolina Cancer
Center, Palmetto Richland Memorial Hospital, Columbia, SC.
The Na+/H+ exchanger isoform 1 (NHE1) is
primarily responsible for the regulation of intracellular pH
(pHi). It is a ubiquitous, amiloride-sensitive, growth
factor-activatable exchanger whose role has been implicated in
cell-cycle regulation, apoptosis, and neoplasia. Here we demonstrate
that leukemic cell lines and peripheral blood from primary patient
leukemic samples exhibit a constitutively and statistically higher
pHi than normal hematopoietic tissue. We then show that a
direct correlation exists between pHi and cell-cycle status
of normal hematopoietic and leukemic cells. Advantage was taken of this
relationship by treating leukemic cells with the
Na+/H+ exchanger inhibitor, 5-(N,
N-hexamethylene)-amiloride (HMA), which decreases the pHi
and induces apoptosis. By incubating patient leukemic cells in vitro
with pharmacologic doses of HMA for up to 5 hours, we show, using flow
cytometry and fluorescent ratio imaging microscopy, that when the
pHi decreases, apoptosis measured by annexin-V and TUNEL
methodologiesrapidly increases so that more than 90% of the
leukemic cells are killed. The differential sensitivity exhibited
between normal and leukemic cells allows consideration of NHE1
inhibitors as potential antileukemic agents.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. HARGUINDEY, J. L. ARRANZ, M. L. WAHL, G. ORIVE, and S. J. RESHKIN
Proton Transport Inhibitors as Potentially Selective Anticancer Drugs
Anticancer Res,
June 1, 2009;
29(6):
2127 - 2136.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Schelling and B. G. Abu Jawdeh
Regulation of cell survival by Na+/H+ exchanger-1
Am J Physiol Renal Physiol,
September 1, 2008;
295(3):
F625 - F632.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Rebillard, X. Tekpli, O. Meurette, O. Sergent, G. LeMoigne-Muller, L. Vernhet, M. Gorria, M. Chevanne, M. Christmann, B. Kaina, et al.
Cisplatin-Induced Apoptosis Involves Membrane Fluidification via Inhibition of NHE1 in Human Colon Cancer Cells
Cancer Res.,
August 15, 2007;
67(16):
7865 - 7874.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. De Milito, E. Iessi, M. Logozzi, F. Lozupone, M. Spada, M. L. Marino, C. Federici, M. Perdicchio, P. Matarrese, L. Lugini, et al.
Proton Pump Inhibitors Induce Apoptosis of Human B-Cell Tumors through a Caspase-Independent Mechanism Involving Reactive Oxygen Species
Cancer Res.,
June 1, 2007;
67(11):
5408 - 5417.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Xue, D. Zhou, H. Yao, O. Gavrialov, M. J. McConnell, B. D. Gelb, and G. G. Haddad
Novel functional interaction between Na+/H+ exchanger 1 and tyrosine phosphatase SHP-2
Am J Physiol Regulatory Integrative Comp Physiol,
June 1, 2007;
292(6):
R2406 - R2416.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. F. Pedersen, M. E. O'Donnell, S. E. Anderson, and P. M. Cala
Physiology and pathophysiology of Na+/H+ exchange and Na+-K+-2Cl- cotransport in the heart, brain, and blood
Am J Physiol Regulatory Integrative Comp Physiol,
July 1, 2006;
291(1):
R1 - R25.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Gonzalez-Gronow, U. K. Misra, G. Gawdi, and S. V. Pizzo
Association of Plasminogen with Dipeptidyl Peptidase IV and Na+/H+ Exchanger Isoform NHE3 Regulates Invasion of Human 1-LN Prostate Tumor Cells
J. Biol. Chem.,
July 22, 2005;
280(29):
27173 - 27178.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Humez, M. Monet, F. van Coppenolle, P. Delcourt, and N. Prevarskaya
The role of intracellular pH in cell growth arrest induced by ATP
Am J Physiol Cell Physiol,
December 1, 2004;
287(6):
C1733 - C1746.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. L. Wu, S. Khan, S. Lakhe-Reddy, L. Wang, G. Jarad, R. T. Miller, M. Konieczkowski, A. M. Brown, J. R. Sedor, and J. R. Schelling
Renal tubular epithelial cell apoptosis is associated with caspase cleavage of the NHE1 Na+/H+ exchanger
Am J Physiol Renal Physiol,
April 1, 2003;
284(4):
F829 - F839.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Pang, S. Wakabayashi, and M. Shigekawa
Expression of Calcineurin B Homologous Protein 2 Protects Serum Deprivation-induced Cell Death by Serum-independent Activation of Na+/H+ Exchanger
J. Biol. Chem.,
November 8, 2002;
277(46):
43771 - 43777.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Coakley, C. Taggart, N. G. McElvaney, and S. J. O'Neill
Cytosolic pH and the inflammatory microenvironment modulate cell death in human neutrophils after phagocytosis
Blood,
October 16, 2002;
100(9):
3383 - 3391.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Marches, E. S. Vitetta, and J. W. Uhr
A role for intracellular pH in membrane IgM-mediated cell death of human B lymphomas
PNAS,
February 22, 2001;
(2001)
61028998.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
R. Marches, E. S. Vitetta, and J. W. Uhr
A role for intracellular pH in membrane IgM-mediated cell death of human B lymphomas
PNAS,
March 13, 2001;
98(6):
3434 - 3439.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
