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The mechanism(s) of post-transcriptional regulation of the human constitutive endothelial nitric oxide synthase gene by tumor necrosis factor-alpha

Title:

The mechanism(s) of post-transcriptional regulation of the human constitutive endothelial nitric oxide synthase gene by tumor necrosis factor-alpha

Mohamed, Farida Y (2000) The mechanism(s) of post-transcriptional regulation of the human constitutive endothelial nitric oxide synthase gene by tumor necrosis factor-alpha. PhD thesis, Concordia University.

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Abstract

Endothelial nitric oxide synthase (eNOS) is an enzyme that catalyzes the formation of nitric oxide (NO) from the amino acid L-arginine and molecular oxygen, with the help of cofactors and a heme iron. It is one of three isoforms discovered as yet, and was first identified in endothelial cells lining the blood vessels. Its product, NO, plays a crucial role in the maintenance of vascular tone and homeostasis. Being a gas, NO can diffuse out of the endothelial cells into the underlying smooth muscle cells to cause vasodilation and into the lumen to prevent the blood platelets and leukocytes from clumping and adhering to the vessel wall. Since eNOS plays a vital role in cell biology, it needs to be tightly regulated. It is expressed constitutively in normal physiological conditions, but may be deregulated in pathophysiological conditions. The purpose of this thesis is to investigate the role of the inflammatory cytokine, tumor necrosis factor-alpha (TNFÌ), in the down-regulation of eNOS expression. It demonstrates that this process occurs at the post-transcriptional level, where TNFÌ is shown to affect the stability of the eNOS transcript, in that it reduces the half-life of the other-wise stable eNOS mRNA. Mechanisms of down-regulation by TNFÌ are explored, involving proteins that bind to the 3 ' untranslated region of the eNOS message.

Divisions:Concordia University > Faculty of Arts and Science > Chemistry and Biochemistry
Item Type:Thesis (PhD)
Authors:Mohamed, Farida Y
Pagination:xx, 224 leaves : ill. ; 29 cm.
Institution:Concordia University
Degree Name:Theses (Ph.D.)
Program:Chemistry and Biochemistry
Date:2000
Thesis Supervisor(s):English, Ann M.
ID Code:1286
Deposited By:Concordia University Libraries
Deposited On:27 Aug 2009 13:18
Last Modified:08 Dec 2010 10:19
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