|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 March 2001, Vol. 97, No. 5, pp. 1306-1313
HEMATOPOIESIS
Unique effects of zinc protoporphyrin on HO-1 induction
and apoptosis
Guang Yang,
Xuandai Nguyen,
Judy Ou,
Prasad Rekulapelli,
David K. Stevenson, and
Phyllis A. Dennery
From the Department of Pediatrics, Stanford University
School of Medicine, Stanford, CA 94305.
Zinc protoporphyrin (ZnPP), a naturally occurring molecule, is
increased in iron deficiency and lead intoxication. ZnPP can also
induce heme oxygenase (HO-1), the enzyme it competitively inhibits. In
cultured cells (HA-1), ZnPP was the strongest HO-1 inducer of any
metalloporphyrin (MP) tested. This was not due to increased oxidative
stress, enhanced binding at metal response element, nor increased
binding at activator protein-1 (AP-1) or SP-1 sites on HO-1.
Only ZnPP, however, increased binding of nuclear proteins to early
growth response-1 (Egr-1) protein consensus sequence. Pretreatment of
HA-1 with cycloheximide inhibited ZnPP-induced HO-1 messenger RNA
(mRNA) by 55%. Incubation with antisense Egr-1 oligomers decreased
ZnPP-induced HO-1 expression by 47%. Furthermore, the level of HO-1
mRNA induction by ZnPP was 2-fold less in Egr-1-deficient fibroblasts
than in wild-type cells. Because no Egr-1 binding site was previously
identified on the HO-1 promoter, HA-1 cells were transfected with HO-1
CAT constructs containing segments of a 12.5-kb enhancer region of
HO-1. A 196-bp fragment (RH) located approximately 9.5 kb upstream of
the transcription start site mediated HO-1 induction by ZnPP alone.
DNase I footprinting analysis further revealed that nuclear proteins
bound to a 50-bp sequence in the RH. Within this sequence, a novel 9-bp
region with 78% homology to the Egr-1 consensus sequence was
identified further suggesting that Egr-1 partially mediates HO-1
induction by ZnPP. Lastly, increased apoptosis and nuclear localization
were only seen with ZnPP, suggesting that increased ZnPP in disease
states may serve as a cellular signaling mechanism.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. D. Mattaliano, C. Huard, W. Cao, A. A. Hill, W. Zhong, R. V. Martinez, D. C. Harnish, J. E. Paulsen, and H. H. Shih
LOX-1-dependent transcriptional regulation in response to oxidized LDL treatment of human aortic endothelial cells
Am J Physiol Cell Physiol,
June 1, 2009;
296(6):
C1329 - C1337.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. El Fadili, M. Imbeault, N. Messier, G. Roy, B. Gourbal, M. Bergeron, M. J. Tremblay, D. Legare, and M. Ouellette
Modulation of Gene Expression in Human Macrophages Treated with the Anti-Leishmania Pentavalent Antimonial Drug Sodium Stibogluconate
Antimicrob. Agents Chemother.,
February 1, 2008;
52(2):
526 - 533.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Gasparyan, G. Hovhannisyan, R. Ghazaryan, L. Sahakyan, A. Tovmasyan, R. Grigoryan, N. Sarkissyan, S. Haroutiunian, and R. Aroutiounian
In Vitro Testing of Cyto- and Genotoxicity of New Porphyrin Water-Soluble Metal Derivatives
International Journal of Toxicology,
November 1, 2007;
26(6):
497 - 502.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Yang, P. J. Lee, L. Long, R. C. Trembath, and N. W. Morrell
BMP4 Induces HO-1 via a Smad-Independent, p38MAPK-Dependent Pathway in Pulmonary Artery Myocytes
Am. J. Respir. Cell Mol. Biol.,
November 1, 2007;
37(5):
598 - 605.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Uc, K. J. Reszka, G. R. Buettner, and J. B. Stokes
Tin protoporphyrin induces intestinal chloride secretion by inducing light oxidation processes
Am J Physiol Cell Physiol,
May 1, 2007;
292(5):
C1906 - C1914.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. W. Ryter, J. Alam, and A. M. K. Choi
Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications
Physiol Rev,
April 1, 2006;
86(2):
583 - 650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. B. Blumenthal, A. K. Kiemer, G. Tiegs, S. Seyfried, M. Holtje, B. Brandt, H.-D. Holtje, S. Zahler, and A. M. Vollmar
Metalloporphyrins inactivate caspase-3 and -8
FASEB J,
August 1, 2005;
19(10):
1272 - 1279.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Lang, S. Reuter, T. Buzescu, C. August, and S. Heidenreich
Heme-induced heme oxygenase-1 (HO-1) in human monocytes inhibits apoptosis despite caspase-3 up-regulation
Int. Immunol.,
February 1, 2005;
17(2):
155 - 165.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Ning, C.-J. Li, N. Kaminski, C. A. Feghali-Bostwick, S. M. Alber, Y. P. Di, S. L. Otterbein, R. Song, S. Hayashi, Z. Zhou, et al.
Comprehensive gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease
PNAS,
October 12, 2004;
101(41):
14895 - 14900.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Kronke, V. N. Bochkov, J. Huber, F. Gruber, S. Bluml, A. Furnkranz, A. Kadl, B. R. Binder, and N. Leitinger
Oxidized Phospholipids Induce Expression of Human Heme Oxygenase-1 Involving Activation of cAMP-responsive Element-binding Protein
J. Biol. Chem.,
December 19, 2003;
278(51):
51006 - 51014.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Fang, T. Sawa, T. Akaike, T. Akuta, S. K. Sahoo, G. Khaled, A. Hamada, and H. Maeda
In Vivo Antitumor Activity of Pegylated Zinc Protoporphyrin: Targeted Inhibition of Heme Oxygenase in Solid Tumor
Cancer Res.,
July 1, 2003;
63(13):
3567 - 3574.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. A. Tulis, W. Durante, X. Liu, A. J. Evans, K. J. Peyton, and A. I. Schafer
Adenovirus-Mediated Heme Oxygenase-1 Gene Delivery Inhibits Injury-Induced Vascular Neointima Formation
Circulation,
November 27, 2001;
104(22):
2710 - 2715.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
