|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 December 2001, Vol. 98, No. 12, pp. 3315-3323
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Redox cycling of diaspirin cross-linked hemoglobin induces G2/M
arrest and apoptosis in cultured endothelial cells
Felice D'Agnillo and
Abdu
I. Alayash
From the Laboratory of Plasma Derivatives, Division of
Hematology, Center for Biologics Evaluation and Research, Food and Drug
Administration, Bethesda, MD.
It is hypothesized that oxidative reactions of hemoglobin driven by
reactive oxygen species in the vasculature lead to endothelial cell
injury or death. Bovine aortic endothelial cells were incubated with
diaspirin cross-linked hemoglobin (DBBF-Hb), developed as a
hemoglobin-based oxygen carrier, and hydrogen peroxide
(H2O2), generated by the glucose oxidase
system. The low steady flux of H2O2 oxidizes
the ferrous form of DBBF-Hb and drives the redox cycling of ferric and
ferryl DBBF-Hb. Cells underwent rounding, swelling and detachment, and
accumulated in the G2/M phase of the cell cycle. G2/M arrest preceded
the onset of apoptosis as determined by increases in phosphatidylserine
(PS) externalization and sub-G1 events. Redox cycling of unmodified
hemoglobin also led to G2/M arrest and apoptosis. The rate and extent
of DBBF-Hb oxidation correlated with the onset and extent of G2/M
arrest and apoptosis and induced significant decreases in soluble
reduced thiols. Earlier depletion of glutathione by pretreatment with buthionine sulfoximine rendered cells more susceptible to G2/M arrest
and apoptosis. The caspase inhibitor, z-VAD-fmk, had no effect on the
induction of G2/M arrest but completely inhibited the subsequent
increases in PS externalization and sub-G1 events. Catalase
inhibited DBBF-Hb oxidation, the loss of thiols, and the onset of
G2/M arrest and apoptosis. These data support a causative role for the
ferric-ferryl redox cycle in the development of endothelial cell injury.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
P. W. Buehler, B. Abraham, F. Vallelian, C. Linnemayr, C. P. Pereira, J. F. Cipollo, Y. Jia, M. Mikolajczyk, F. S. Boretti, G. Schoedon, et al.
Haptoglobin preserves the CD163 hemoglobin scavenger pathway by shielding hemoglobin from peroxidative modification
Blood,
March 12, 2009;
113(11):
2578 - 2586.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Brisson, T. Nguyen, P. Wipf, B. Joo, B. W. Day, J. S. Skoko, E. M. Schreiber, C. Foster, P. Bansal, and J. S. Lazo
Redox Regulation of Cdc25B by Cell-Active Quinolinediones
Mol. Pharmacol.,
December 1, 2005;
68(6):
1810 - 1820.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Cabrales, A. G. Tsai, and M. Intaglietta
Increased tissue PO2 and decreased O2 delivery and consumption after 80% exchange transfusion with polymerized hemoglobin
Am J Physiol Heart Circ Physiol,
December 1, 2004;
287(6):
H2825 - H2833.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. D'Agnillo
Redox active hemoglobin enhances lipopolysaccharide-induced injury to cultured bovine endothelial cells
Am J Physiol Heart Circ Physiol,
October 1, 2004;
287(4):
H1875 - H1882.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. I. Ginsburg and A. L. Baldwin
Disodium cromoglycate stabilizes mast cell degranulation while reducing the number of hemoglobin-induced microvascular leaks in rat mesentery
Am J Physiol Heart Circ Physiol,
May 1, 2004;
286(5):
H1750 - H1756.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Baldwin, E. B. Wiley, and A. I. Alayash
Comparison of effects of two hemoglobin-based O2 carriers on intestinal integrity and microvascular leakage
Am J Physiol Heart Circ Physiol,
October 1, 2002;
283(4):
H1292 - H1301.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Savitsky and T. Finkel
Redox Regulation of Cdc25C
J. Biol. Chem.,
May 31, 2002;
277(23):
20535 - 20540.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
