Regarding COX-2 which of the following is its function aEUR'
Cell proliferation ? ? ? The enzymes that conve arachidonic acid to prostaglandin H2 are named cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) (original name was prostaglandin H synthase). The propeies of COX-1 are different from those of COX-2. It was originally thought that the. function of COX-1 was involved in physiological phenomena where as that of COX-2 was involved in various pathologies. COX-1 is considered as the constitutive enzyme or the housekeeping enzyme that is naturally expressed on all cell surfaces. COX-2 is known as inducible enzyme which is not naturally expressed on the cells but is expressed on stimulation of cells. Functions of COX-1 and COX-2 Inflammation During inflammation, COX-1 mRNA, protein and activity levels do not change, but COX-2 levels increase dramatically, and as a result prostaglandin production increases. - Moreover, when COX-2 specific inhibitors are administered, prostaglandin production and subsequent inflammation are significantly reduced. - These data have lead to the conclusion that COX-2 is involved in inflammation whereas COX-1 is not. - During the inflammation process, COX-I is though to contribute to resolution. The COX-2 gene is paicularly responsive to mediators of inflammation. - For example, IL-la, IL-I b, TNF-a and LPS induce COX-2 gene expression and subsequent prostaglandin production. Therefore COX-2 inhibitors have been used to attenuate the symptoms of inflammation such as osteoahritis, rheumatoid ahritis and musculoskeletal pains. Cardiovascular system It is well known that the platelet has COX-1 protein alone (no COX-2). The thromboxane A2 produced COX-1 has an impoant role in thrombosis. - It has been thought that vascular endothelial cells and smooth muscle cells have COX-1 and that prostacyclin formed COX-1 has an impoant role in blood flow, blood pressure and antiaggregation of platelets. However, a recent work has shown that prostacyclin in vascular cells is produced by COX-2 as well as COX-1 under both physiological and pathological conditions. - These results raised the possibility of an increased risk of cardiovascular events associated with COX-2 specific inhibitors. However, trials have not confirmed these results. Tumorigenesis COX-2 causes tumorigenesis and tumour growth. - Overexpression of COX-2 in tumor cells causes cells to escape from apoptosis and to invade the matrix. - The contribution of COX-2 to tumorigenesis is mainly through three processes. a) Induction of angiogenic,factors such as VEGF b) Antiapoptosis and c) Development of malignancy In vivo, tumour associated macrophages as well as tumor cells produce "PGE2 COX-2" and the PGE2 produced, induces VEGF and finally VEGF stimulates angiogenesis. Renal function COX-1 is primarily expressed in podocytes and collecting duct cells and is involved in glomerulogenesis. COX-2 is detected in renal vasculature, medullary interstitial cells and the macula densa. COX-2 is involved in renal perfusion and glomerular hemodynamics. Cyclooxygenase function can also be assessed by disrupting COX-1 and COX-2 genes in mice COX-2 deficient mice demonstrates following :- Defect in female reproductive functions including ovulation, feilization and implantation and decidualization Reduction in brain injury induced by ischemia Suppression of tumorigenesis Renal nephropathy Cardiac.fibrosis Peritonitis Failure of ductus aeriosus closure Even after this extensive discussion, 1 am not sure about the answer. Since COX-2 has a role in the development of twnorigenesis, cell proliferation seems to be the appropriate answer. COX-2 causes tumorigenesis by induction of VEGF. VEGF is vascular endothelial growth factor and it causes endothelial proliferation. We are not sure of the answer. Go through the .following sites on internet. http//www.ncbi.nlm.gov/pubmed/18039779; http/Avvvw.ncbi.nlin.nih.gov/pubmed/12045254; Jun invest 2002 June 109 (11/1405=15); www.ncbi.nlm. gov/pubmed/16219005; http//www.ncbi.nlm. nih.gov/pubmed/12444028 COX-2 seems to regulate all the ,functions mentioned in the question. We have looked into numerous texts and internet sites for this one. But we cannot come up with some conclusive material on this one. There are ceain texts which say that COX-2 is implicated in tumors genesis through all the following mechanisms Cellular proliferation Antiapoptosis Cellular differentiation Cellular migration Cellular adhesion If the question is repeated again with the same options we would go for cellular proliferation.
Cell adhesion
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Cell migration
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