Abstract

and specific aims): Angiotensin 1 converting enzyme causes both vasoconstriction and vascular wall remodeling through the formation of angiotensin 2 and possibly by an activation of bradykinin. Alterations in ACE may participate in hypoxia-induced pulmonary hypertension. Thus, regulation of the synthesis of ACE is an important physiologic event in need of further study.
The specific aims of this proposal are: 1) To better define mechanisms by which elevations of ACE occur by analysis of ACE gene transcription using nuclear run-off and mRNA stability by half-life studies; 2) To determine the role of promoter regions of the gene in the stimulation of ACE mRNA synthesis, with particular reference to oxygen-sensing response elements, by functional promoter analysis in transfected cells; and 3) To delineate specific promoter elements by DNase footprinting and assess the factors that bind these elements by electrophoretic mobility shift assay.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL014456-27
Application #
6182838
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1975-09-01
Project End
2002-06-30
Budget Start
2000-07-01
Budget End
2002-06-30
Support Year
27
Fiscal Year
2000
Total Cost
$374,702
Indirect Cost

  Institution

Name
Tufts University
Department
Type
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111

  Publications

Day, R M; Yang, Y; Suzuki, Y J et al. (2001) Bleomycin upregulates gene expression of angiotensin-converting enzyme via mitogen-activated protein kinase and early growth response 1 transcription factor. Am J Respir Cell Mol Biol 25:613-9
Stevens, J; Yu, F S; Hassoun, P M et al. (1996) Quantification of polymerase chain reaction products: enzyme immunoassay based systems for digoxigenin- and biotin-labelled products that quantify either total or specific amplicons. Mol Cell Probes 10:31-41
Lazarus, D S; Aschoff, J; Fanburg, B L et al. (1994) Angiotensin converting enzyme (kininase II) mRNA production and enzymatic activity in human peripheral blood monocytes are induced by GM-CSF but not by other cytokines. Biochim Biophys Acta 1226:12-8
Lanzillo, J J; Kong, X J; Fanburg, B L (1994) A competitive deletion mutant quantitative PCR assay for angiotensin-converting enzyme mRNA in smooth muscle cells. PCR Methods Appl 4:167-71
Aschoff, J M; Lazarus, D; Fanburg, B L et al. (1994) Relative quantification of angiotensin-converting enzyme mRNA in human smooth muscle cells, monocytes, and lymphocytes by the polymerase chain reaction. Anal Biochem 219:218-23
Hassoun, P M; Yu, F S; Shedd, A L et al. (1994) Regulation of endothelial cell xanthine dehydrogenase xanthine oxidase gene expression by oxygen tension. Am J Physiol 266:L163-71
Dasarathy, Y; Lanzillo, J J; Fanburg, B L (1992) Stimulation of bovine pulmonary artery endothelial cell ACE by dexamethasone: involvement of steroid receptors. Am J Physiol 263:L645-9
Hassoun, P M; Shedd, A L; Lanzillo, J J et al. (1992) Inhibition of pulmonary artery smooth muscle cell growth by hypoxanthine, xanthine, and uric acid. Am J Respir Cell Mol Biol 6:617-24
White, A C; Das, S K; Fanburg, B L (1992) Reduction of glutathione is associated with growth restriction and enlargement of bovine pulmonary artery endothelial cells produced by transforming growth factor-beta 1. Am J Respir Cell Mol Biol 6:364-8
Dasarathy, Y; Fanburg, B L (1991) Involvement of second messenger systems in stimulation of angiotensin converting enzyme of bovine endothelial cells. J Cell Physiol 148:327-35

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