Abstract
Changes in endothelial nitric oxide synthase (eNOS) expression may be involved in the endothelium-dependent vasorelaxation dysfunction associated with several vascular diseases. In the present work, we demonstrate that eNOS mRNA contains a previously undescribed cis element in the 3' untranslated region (3' UTR). A U+C-rich segment in the 3' UTR is critical in complex formation with bovine aortic endothelial cell cytosolic proteins. Tumor necrosis factor alpha (TNF-alpha), which destabilizes eNOS mRNA, increased the binding activity of the cytosolic proteins in a time-dependent manner. These data suggest that endothelial cytosolic proteins bind to the 3' UTR of eNOS mRNA. These proteins may play a role in TNF-alpha-induced eNOS mRNA destabilization.
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- Akashi M., Shaw G., Hachiya M., Elstner E., Suzuki G., Koeffler P. Number and location of AUUUA motifs: role in regulating transiently expressed RNAs. Blood. 1994 Jun 1;83(11):3182–3187. [PubMed] [Google Scholar]
- Barath P., Fishbein M. C., Cao J., Berenson J., Helfant R. H., Forrester J. S. Tumor necrosis factor gene expression in human vascular intimal smooth muscle cells detected by in situ hybridization. Am J Pathol. 1990 Sep;137(3):503–509. [PMC free article] [PubMed] [Google Scholar]
- Bickel M., Iwai Y., Pluznik D. H., Cohen R. B. Binding of sequence-specific proteins to the adenosine- plus uridine-rich sequences of the murine granulocyte/macrophage colony-stimulating factor mRNA. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10001–10005. doi: 10.1073/pnas.89.21.10001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bohjanen P. R., Petryniak B., June C. H., Thompson C. B., Lindsten T. An inducible cytoplasmic factor (AU-B) binds selectively to AUUUA multimers in the 3' untranslated region of lymphokine mRNA. Mol Cell Biol. 1991 Jun;11(6):3288–3295. doi: 10.1128/mcb.11.6.3288. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brewer G. An A + U-rich element RNA-binding factor regulates c-myc mRNA stability in vitro. Mol Cell Biol. 1991 May;11(5):2460–2466. doi: 10.1128/mcb.11.5.2460. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carter B. Z., Malter J. S. Regulation of mRNA stability and its relevance to disease. Lab Invest. 1991 Dec;65(6):610–621. [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- Czyzyk-Krzeska M. F., Dominski Z., Kole R., Millhorn D. E. Hypoxia stimulates binding of a cytoplasmic protein to a pyrimidine-rich sequence in the 3'-untranslated region of rat tyrosine hydroxylase mRNA. J Biol Chem. 1994 Apr 1;269(13):9940–9945. [PubMed] [Google Scholar]
- Dodson R. E., Shapiro D. J. An estrogen-inducible protein binds specifically to a sequence in the 3' untranslated region of estrogen-stabilized vitellogenin mRNA. Mol Cell Biol. 1994 May;14(5):3130–3138. doi: 10.1128/mcb.14.5.3130. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Geneste O., Raffalli F., Lang M. A. Identification and characterization of a 44 kDa protein that binds specifically to the 3'-untranslated region of CYP2a5 mRNA: inducibility, subcellular distribution and possible role in mRNA stabilization. Biochem J. 1996 Feb 1;313(Pt 3):1029–1037. doi: 10.1042/bj3131029. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jackson R. J. Cytoplasmic regulation of mRNA function: the importance of the 3' untranslated region. Cell. 1993 Jul 16;74(1):9–14. doi: 10.1016/0092-8674(93)90290-7. [DOI] [PubMed] [Google Scholar]
- Le Cras T. D., Xue C., Rengasamy A., Johns R. A. Chronic hypoxia upregulates endothelial and inducible NO synthase gene and protein expression in rat lung. Am J Physiol. 1996 Jan;270(1 Pt 1):L164–L170. doi: 10.1152/ajplung.1996.270.1.L164. [DOI] [PubMed] [Google Scholar]
- Levine B., Kalman J., Mayer L., Fillit H. M., Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med. 1990 Jul 26;323(4):236–241. doi: 10.1056/NEJM199007263230405. [DOI] [PubMed] [Google Scholar]
- Ludmer P. L., Selwyn A. P., Shook T. L., Wayne R. R., Mudge G. H., Alexander R. W., Ganz P. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986 Oct 23;315(17):1046–1051. doi: 10.1056/NEJM198610233151702. [DOI] [PubMed] [Google Scholar]
- López Farré A., Mosquera J. R., Sánchez de Miguel L., Millás I., de Frutos T., Montón M., Sierra M. P., Riesco A., Casado S. Endothelial cells inhibit NO generation by vascular smooth muscle cells. Role of transforming growth factor-beta. Arterioscler Thromb Vasc Biol. 1996 Oct;16(10):1263–1268. doi: 10.1161/01.atv.16.10.1263. [DOI] [PubMed] [Google Scholar]
- López Farré A., Riesco A., Espinosa G., Digiuni E., Cernadas M. R., Alvarez V., Montón M., Rivas F., Gallego M. J., Egido J. Effect of endothelin-1 on neutrophil adhesion to endothelial cells and perfused heart. Circulation. 1993 Sep;88(3):1166–1171. doi: 10.1161/01.cir.88.3.1166. [DOI] [PubMed] [Google Scholar]
- López-Farré A., Caramelo C., Esteban A., Alberola M. L., Millás I., Montón M., Casado S. Effects of aspirin on platelet-neutrophil interactions. Role of nitric oxide and endothelin-1. Circulation. 1995 Apr 1;91(7):2080–2088. doi: 10.1161/01.cir.91.7.2080. [DOI] [PubMed] [Google Scholar]
- López-Farré A., Sánchez de Miguel L., Caramelo C., Gómez-Macías J., Garcia R., Mosquera J. R., de Frutos T., Millás I., Rivas F., Echezarreta G. Role of nitric oxide in autocrine control of growth and apoptosis of endothelial cells. Am J Physiol. 1997 Feb;272(2 Pt 2):H760–H768. doi: 10.1152/ajpheart.1997.272.2.H760. [DOI] [PubMed] [Google Scholar]
- Ma X. L., Weyrich A. S., Lefer D. J., Lefer A. M. Diminished basal nitric oxide release after myocardial ischemia and reperfusion promotes neutrophil adherence to coronary endothelium. Circ Res. 1993 Feb;72(2):403–412. doi: 10.1161/01.res.72.2.403. [DOI] [PubMed] [Google Scholar]
- Marsden P. A., Schappert K. T., Chen H. S., Flowers M., Sundell C. L., Wilcox J. N., Lamas S., Michel T. Molecular cloning and characterization of human endothelial nitric oxide synthase. FEBS Lett. 1992 Aug 3;307(3):287–293. doi: 10.1016/0014-5793(92)80697-f. [DOI] [PubMed] [Google Scholar]
- Mohamed F., Monge J. C., Gordon A., Cernacek P., Blais D., Stewart D. J. Lack of role for nitric oxide (NO) in the selective destabilization of endothelial NO synthase mRNA by tumor necrosis factor-alpha. Arterioscler Thromb Vasc Biol. 1995 Jan;15(1):52–57. doi: 10.1161/01.atv.15.1.52. [DOI] [PubMed] [Google Scholar]
- Moncada S., Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med. 1993 Dec 30;329(27):2002–2012. doi: 10.1056/NEJM199312303292706. [DOI] [PubMed] [Google Scholar]
- Müllner E. W., Kühn L. C. A stem-loop in the 3' untranslated region mediates iron-dependent regulation of transferrin receptor mRNA stability in the cytoplasm. Cell. 1988 Jun 3;53(5):815–825. doi: 10.1016/0092-8674(88)90098-0. [DOI] [PubMed] [Google Scholar]
- Port J. D., Huang L. Y., Malbon C. C. Beta-adrenergic agonists that down-regulate receptor mRNA up-regulate a M(r) 35,000 protein(s) that selectively binds to beta-adrenergic receptor mRNAs. J Biol Chem. 1992 Nov 25;267(33):24103–24108. [PubMed] [Google Scholar]
- Radomski M. W., Palmer R. M., Moncada S. Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium. Lancet. 1987 Nov 7;2(8567):1057–1058. doi: 10.1016/s0140-6736(87)91481-4. [DOI] [PubMed] [Google Scholar]
- Ross J. mRNA stability in mammalian cells. Microbiol Rev. 1995 Sep;59(3):423–450. doi: 10.1128/mr.59.3.423-450.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seiser C., Posch M., Thompson N., Kühn L. C. Effect of transcription inhibitors on the iron-dependent degradation of transferrin receptor mRNA. J Biol Chem. 1995 Dec 8;270(49):29400–29406. doi: 10.1074/jbc.270.49.29400. [DOI] [PubMed] [Google Scholar]
- Sessa W. C., Pritchard K., Seyedi N., Wang J., Hintze T. H. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res. 1994 Feb;74(2):349–353. doi: 10.1161/01.res.74.2.349. [DOI] [PubMed] [Google Scholar]
- Sessa W. C. The nitric oxide synthase family of proteins. J Vasc Res. 1994 May-Jun;31(3):131–143. doi: 10.1159/000159039. [DOI] [PubMed] [Google Scholar]
- Stephens J. M., Carter B. Z., Pekala P. H., Malter J. S. Tumor necrosis factor alpha-induced glucose transporter (GLUT-1) mRNA stabilization in 3T3-L1 preadipocytes. Regulation by the adenosine-uridine binding factor. J Biol Chem. 1992 Apr 25;267(12):8336–8341. [PubMed] [Google Scholar]
- Vakalopoulou E., Schaack J., Shenk T. A 32-kilodalton protein binds to AU-rich domains in the 3' untranslated regions of rapidly degraded mRNAs. Mol Cell Biol. 1991 Jun;11(6):3355–3364. doi: 10.1128/mcb.11.6.3355. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang X., Kiledjian M., Weiss I. M., Liebhaber S. A. Detection and characterization of a 3' untranslated region ribonucleoprotein complex associated with human alpha-globin mRNA stability. Mol Cell Biol. 1995 Mar;15(3):1769–1777. doi: 10.1128/mcb.15.3.1769. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wong G. G., Witek J. S., Temple P. A., Wilkens K. M., Leary A. C., Luxenberg D. P., Jones S. S., Brown E. L., Kay R. M., Orr E. C. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985 May 17;228(4701):810–815. doi: 10.1126/science.3923623. [DOI] [PubMed] [Google Scholar]
- Yoshizumi M., Perrella M. A., Burnett J. C., Jr, Lee M. E. Tumor necrosis factor downregulates an endothelial nitric oxide synthase mRNA by shortening its half-life. Circ Res. 1993 Jul;73(1):205–209. doi: 10.1161/01.res.73.1.205. [DOI] [PubMed] [Google Scholar]