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Regulation of endothelial cell xanthine dehydrogenase xanthine oxidase gene expression by oxygen tension.
Am J Physiol. 1994 Feb; 266(2 Pt 1):L163-71.AJ

Abstract

Recent studies have demonstrated that xanthine dehydrogenase/xanthine oxidase (XD/XO) activities of bovine endothelial cells (EC) are inversely regulated by O2 tensions to which the cells are exposed. We have confirmed these reports and extended the observation to a variety of cells from other sources. All EC that had detectable XD/XO activity demonstrated the greatest activity at the lowest O2 level. Bovine pulmonary artery smooth muscle cells showed XD/XO activity only under hypoxic conditions. The ratio of XO to XO+XD did not change significantly under various O2 concentrations for all cell types tested. Treatment of bovine pulmonary artery and rat epididymal fat pad EC with actinomycin D (1 microgram/ml), an inhibitor of transcription, suppressed XO and XO+XD activities in cells exposed both to 20 and 3% O2. High-dose cycloheximide (5 micrograms/ml), an inhibitor of translation, also reduced XO and XO+XD activities in these cells, whereas low-dose cycloheximide (0.5 microgram/ml) enhanced the stimulatory effect of hypoxia on XO+XD activity. We developed a digoxigenin-labeled probe that recognizes and hybridizes to rat XD cDNA and used it to examine the effect of O2 concentration on XD/XO mRNA expression of rat epididymal fat pad EC. XD/XO mRNA concentration was increased in cells exposed to hypoxia and decreased in cells exposed to hyperoxia compared with normoxic cells. The increase in mRNA concentration resulting from exposure to hypoxia was enhanced by cycloheximide. There was no change in XD/XO mRNA stability in cells exposed to hypoxia compared with normoxia. We conclude that the regulation of XD/XO by oxygen tension most likely occurs at the transcriptional level.

Authors+Show Affiliations

Department of Medicine, New England Medical Center/Tufts University School of Medicine, Boston, Massachusetts 02111.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8141312

Citation

Hassoun, P M., et al. "Regulation of Endothelial Cell Xanthine Dehydrogenase Xanthine Oxidase Gene Expression By Oxygen Tension." The American Journal of Physiology, vol. 266, no. 2 Pt 1, 1994, pp. L163-71.
Hassoun PM, Yu FS, Shedd AL, et al. Regulation of endothelial cell xanthine dehydrogenase xanthine oxidase gene expression by oxygen tension. Am J Physiol. 1994;266(2 Pt 1):L163-71.
Hassoun, P. M., Yu, F. S., Shedd, A. L., Zulueta, J. J., Thannickal, V. J., Lanzillo, J. J., & Fanburg, B. L. (1994). Regulation of endothelial cell xanthine dehydrogenase xanthine oxidase gene expression by oxygen tension. The American Journal of Physiology, 266(2 Pt 1), L163-71.
Hassoun PM, et al. Regulation of Endothelial Cell Xanthine Dehydrogenase Xanthine Oxidase Gene Expression By Oxygen Tension. Am J Physiol. 1994;266(2 Pt 1):L163-71. PubMed PMID: 8141312.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of endothelial cell xanthine dehydrogenase xanthine oxidase gene expression by oxygen tension. AU - Hassoun,P M, AU - Yu,F S, AU - Shedd,A L, AU - Zulueta,J J, AU - Thannickal,V J, AU - Lanzillo,J J, AU - Fanburg,B L, PY - 1994/2/1/pubmed PY - 1994/2/1/medline PY - 1994/2/1/entrez SP - L163 EP - 71 JF - The American journal of physiology JO - Am J Physiol VL - 266 IS - 2 Pt 1 N2 - Recent studies have demonstrated that xanthine dehydrogenase/xanthine oxidase (XD/XO) activities of bovine endothelial cells (EC) are inversely regulated by O2 tensions to which the cells are exposed. We have confirmed these reports and extended the observation to a variety of cells from other sources. All EC that had detectable XD/XO activity demonstrated the greatest activity at the lowest O2 level. Bovine pulmonary artery smooth muscle cells showed XD/XO activity only under hypoxic conditions. The ratio of XO to XO+XD did not change significantly under various O2 concentrations for all cell types tested. Treatment of bovine pulmonary artery and rat epididymal fat pad EC with actinomycin D (1 microgram/ml), an inhibitor of transcription, suppressed XO and XO+XD activities in cells exposed both to 20 and 3% O2. High-dose cycloheximide (5 micrograms/ml), an inhibitor of translation, also reduced XO and XO+XD activities in these cells, whereas low-dose cycloheximide (0.5 microgram/ml) enhanced the stimulatory effect of hypoxia on XO+XD activity. We developed a digoxigenin-labeled probe that recognizes and hybridizes to rat XD cDNA and used it to examine the effect of O2 concentration on XD/XO mRNA expression of rat epididymal fat pad EC. XD/XO mRNA concentration was increased in cells exposed to hypoxia and decreased in cells exposed to hyperoxia compared with normoxic cells. The increase in mRNA concentration resulting from exposure to hypoxia was enhanced by cycloheximide. There was no change in XD/XO mRNA stability in cells exposed to hypoxia compared with normoxia. We conclude that the regulation of XD/XO by oxygen tension most likely occurs at the transcriptional level. SN - 0002-9513 UR - https://www.unboundmedicine.com/medline/citation/8141312/Regulation_of_endothelial_cell_xanthine_dehydrogenase_xanthine_oxidase_gene_expression_by_oxygen_tension_ L2 - https://journals.physiology.org/doi/10.1152/ajplung.1994.266.2.L163?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -