|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 May 2002, Vol. 99, No. 9, pp. 3205-3212
HEMATOPOIESIS
Vitamin C inhibits granulocyte macrophage-colony-stimulating
factor-induced signaling pathways
Juan M. Cárcamo,
Oriana Bórquez-Ojeda, and
David W. Golde
From the Program in Molecular Pharmacology and
Therapeutics, and the Departments of Clinical Chemistry and Medicine,
Memorial Sloan-Kettering Cancer Center, New York, NY.
Vitamin C is present in the cytosol as ascorbic acid, functioning
primarily as a cofactor for enzymatic reactions and as an antioxidant
to scavenge free radicals. Human granulocyte
macrophage-colony-stimulating factor (GM-CSF) induces an increase in
reactive oxygen species (ROS) and uses ROS for some signaling
functions. We therefore investigated the effect of vitamin C on
GM-CSF-mediated responses. Loading U937 cells with vitamin C decreased
intracellular levels of ROS and inhibited the production of ROS induced
by GM-CSF. Vitamin C suppressed GM-CSF-dependent phosphorylation of
the signal transducer and activator of transcription 5 (Stat-5) and
mitogen-activated protein (MAP) kinase (Erk1 and Erk2) in a
dose-dependent manner as was phosphorylation of MAP kinase induced by
both interleukin 3 (IL-3) and GM-CSF in HL-60 cells. In 293T cells
transfected with alpha and beta GM-CSF receptor subunits ( GMR and
 GMR), GM-CSF-induced phosphorylation of GMR and Jak-2 activation
was suppressed by vitamin C loading. GM-CSF-mediated transcriptional activation of a luciferase reporter construct containing STAT-binding sites was also inhibited by vitamin C. These results substantiate the
importance of ROS in GM-CSF signaling and indicate a role for vitamin C
in downmodulating GM-CSF signaling responses. Our findings point to
vitamin C as a regulator of cytokine redox-signal transduction in host
defense cells and a possible role in controlling inflammatory responses.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. Wang, G. Muxin, H. Nishida, C. Shirakawa, S. Sato, and T. Konishi
Psychological Stress-Induced Oxidative Stress as a Model of Sub-Healthy Condition and the Effect of TCM
Evid. Based Complement. Altern. Med.,
June 1, 2007;
4(2):
195 - 202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. K. Chun, S. J. Chung, and W. O. Song
Estimated Dietary Flavonoid Intake and Major Food Sources of U.S. Adults
J. Nutr.,
May 1, 2007;
137(5):
1244 - 1252.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Piccoli, R. Ria, R. Scrima, O. Cela, A. D'Aprile, D. Boffoli, F. Falzetti, A. Tabilio, and N. Capitanio
Characterization of Mitochondrial and Extra-mitochondrial Oxygen Consuming Reactions in Human Hematopoietic Stem Cells: NOVEL EVIDENCE OF THE OCCURRENCE OF NAD(P)H OXIDASE ACTIVITY
J. Biol. Chem.,
July 15, 2005;
280(28):
26467 - 26476.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Karasavvas, J. M. Carcamo, G. Stratis, and D. W. Golde
Vitamin C protects HL60 and U266 cells from arsenic toxicity
Blood,
May 15, 2005;
105(10):
4004 - 4012.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. J. DeYulia Jr., J. M. Carcamo, O. Borquez-Ojeda, C. C. Shelton, and D. W. Golde
Hydrogen peroxide generated extracellularly by receptor-ligand interaction facilitates cell signaling
PNAS,
April 5, 2005;
102(14):
5044 - 5049.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Carcamo, A. Pedraza, O. Borquez-Ojeda, B. Zhang, R. Sanchez, and D. W. Golde
Vitamin C Is a Kinase Inhibitor: Dehydroascorbic Acid Inhibits I{kappa}B{alpha} Kinase {beta}
Mol. Cell. Biol.,
August 1, 2004;
24(15):
6645 - 6652.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ebner, A. Bandion, B. R. Binder, R. de Martin, and J. A. Schmid
GMCSF activates NF-{kappa}B via direct interaction of the GMCSF receptor with I{kappa}B kinase {beta}
Blood,
July 1, 2003;
102(1):
192 - 199.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Perez-Cruz, J. M. Carcamo, and D. W. Golde
Vitamin C inhibits FAS-induced apoptosis in monocytes and U937 cells
Blood,
July 1, 2003;
102(1):
336 - 343.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. W. Golde
Vitamin C in Cancer
Integr Cancer Ther,
June 1, 2003;
2(2):
158 - 159.
[PDF]
|
|
|
|
|
|
|
M. Dhar-Mascareno, J. Chen, R. H. Zhang, J. M. Carcamo, and D. W. Golde
Granulocyte-Macrophage Colony-stimulating Factor Signals for Increased Glucose Transport via Phosphatidylinositol 3-Kinase- and Hydrogen Peroxide-dependent Mechanisms
J. Biol. Chem.,
March 21, 2003;
278(13):
11107 - 11114.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. Gardai, R. Hoontrakoon, C. D. Goddard, B. J. Day, L. Y. Chang, P. M. Henson, and D. L. Bratton
Oxidant-Mediated Mitochondrial Injury in Eosinophil Apoptosis: Enhancement by Glucocorticoids and Inhibition by Granulocyte-Macrophage Colony-Stimulating Factor
J. Immunol.,
January 1, 2003;
170(1):
556 - 566.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
