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Vol. 293, Issue 2, 494-500, May 2000
The Rockefeller University, New York, New York (N.G.A., S.J.,
G.S.D., A.K.); and Department of Pharmacology, New York Medical
College, Valhalla, New York (L.Y., B.A.Z., M.L.-S., J.M.)
Intravenous administration of an adenovirus human heme oxygenase (HO)-1
gene construct to rats resulted in functional expression of human HO-1
in brain, heart, lung, liver, and kidney. Because accurate assessment
of human HO-1 mRNA in various tissues by Northern analysis is not
sufficiently sensitive, we developed a method for quantifying human
HO-1 mRNA copies with quantitative reverse transcription- polymerase
chain reaction techniques; this allowed us to use the same primers for
both the sample and internal standard. Administration of the adenovirus
human HO-1 gene resulted in the detection of human HO-1 mRNA in various
tissues with the highest levels seen in the kidney followed, in order,
by lung > liver > brain > heart. Human HO-1 was
detectable for up to 4 weeks in all tissues studied. Administration of
adenovirus human HO-1 resulted in maximal increase of HO activity after
1 to 2 weeks in rats. The increase in HO activity due to gene transfer
also was associated with a parallel decrease (~25%) in cytochrome
P-450 (CYP) content and in CYP-dependant arachidonic acid metabolism.
In addition, we investigated the possibility that the human HO-1 gene
altered the expression of the endogenous rat enzyme after
administration of cobalt chloride s.c.. Cobalt chloride administration
resulted in increased HO activity in all tissues examined in rats
transduced with the human HO-1 gene to the same degree as in
nontransduced rats. The metal was a more potent inducer of renal HO
activity than was the adenoviral-mediated human HO-1 vector. The
increase in HO activity after adenoviral-mediated human HO-1 transfer
was associated with a decrease in microsomal heme-CYP and CYP activity. The increase in HO-1 activity after adenovirus-mediated human HO-1 gene
transfer may prove useful as a means of selectively increasing enzyme
activity in a specific organ and regulating homeostasis by modulation
of vasoactive molecules such as carbon monoxide and bilirubin and, in
addition, providing a means of delivering the human HO-1 gene for
experimental purposes.
This article has been cited by other articles:
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  N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF]
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 J.-S. Wang, H. Singh, F. Zhang, T. Ishizuka, H. Deng, R. Kemp, M. S. Wolin, T. H. Hintze, N. G. Abraham, A. Nasjletti, et al. Endothelial Dysfunction and Hypertension in Rats Transduced With CYP4A2 Adenovirus Circ. Res., April 14, 2006; 98(7): 962 - 969. [Abstract] [Full Text] [PDF]
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 N. G. Abraham, S. Quan, P. A. Mieyal, L. Yang, T. Burke-Wolin, C. J. Mingone, A. I. Goodman, A. Nasjletti, and M. S. Wolin Modulation of cGMP by human HO-1 retrovirus gene transfer in pulmonary microvessel endothelial cells Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L1117 - L1124. [Abstract] [Full Text] [PDF]
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 F. T. Botros, M. Laniado-Schwartzman, and N. G. Abraham Regulation of Cyclooxygenase- and Cytochrome P450-Derived Eicosanoids by Heme Oxygenase in the Rat Kidney Hypertension, February 1, 2002; 39(2): 639 - 644. [Abstract] [Full Text] [PDF]
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 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]
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 S. Quan, L. Yang, N. G. Abraham, and A. Kappas Regulation of human heme oxygenase in endothelial cells by using sense and antisense retroviral constructs PNAS, October 9, 2001; 98(21): 12203 - 12208. [Abstract] [Full Text] [PDF]
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