COX-2

Related Reading

Prostaglandin-endop-eroxide synthase (PTGS), also known as cycloox-ygenase (COX), is the key enzyme in the initial step of prostaglandin (PG) synthesis in the organism. Biologically active lipid regulators include precursors of various families such as prostaglandins, thromboxanes and prostacyclins. There are two isozymes of PTGS: structural type (PTGS 1) and inducible type (PTGS2), both of which are at the expression level, gene regulation and molecular characteristics. There are very significant differences. As early as 20 years ago, the prostaglandin endoperoxidase synthase 1 gene was isolated and identified from the seminal vesicle glands of cattle and sheep. In recent years, the prostaglandin endoperoxidase 2 gene cloned from chick and mouse fibroblasts and purified from rat granulosa cells has been proven to play an important role in many pathophysiological processes.

Figure 1. Protein structure of COX2.

Biology

In terms of their molecular biology, COX-1 and COX-2 are of similar molecular weight, approximately 70 and 72 kDa, respectively, and having 65% amino acid sequence homology and near-identical catalytic sites. Both proteins have three domains: an N-terminal EGF-like domain, a small 4-helical membrane anchor, and a core heme-peroxidase catalytic domain. Both form dimers.The membrane anchor fixes the proteins into the endoplasmic reticulum (ER) and microsome membrane

Comparison of PTGS2 and PTGS1

Both PTGS1 and PTGS2 are integral membrane proteins. cDNA cloning analysis showed that the 2.8kb human PTGS1 gene mRNA encodes 599 or 600 amino acid residues, including a signal peptide consisting of 23 or 24 amino acid residues, while the 4-4.5kb human PTGS2 gene mRNA encodes 603 amino acid residues. Or 604 amino acids, including a signal peptide composed of 17 amino acid residues. The molecular masses of sheep PTGS1 and PTGS2 are about 72 kD on SDS-PAGE. Another site of the glycosylation of the PTGS 2 gene shows another band of 74 kD. The amino acid sequences determined by the two enzymes within species have approximately 59% to 61% homology, while PTGS2 has 90% homology between species. Compared with the PTGS1 gene, the PTGS2 gene contains an additional 18 amino acids at the C-terminus. These 18 amino acids may produce specific antibodies to inhibit the expression of PTGS2.

Conclusion

Prostaglandins have a wide range of biological effects in the body. Prostaglandin endoperoxidase 2 plays a key role in regulating the synthesis of prostaglandins. It is divided into two isozymes of structural type (PTGS1) and inducible type (PTGS2), nd there is a very significant difference between the two. Mutations in the PTGS2 gene generated by external stimuli lead to the lack of corpus luteum during ovarian development, the mutation of oocytes, and the failure to excrete the first polar body, resulting in the failure of many animals to reproduce. Therefore, in-depth study of the mechanism of PTGS2 gene in animal reproduction has important scientific significance.

Cardiovascular side effects of COX inhibitors

It has been found that even short-term use of COX-2 inhibitors can increase the risk of arterial thrombosis. An analysis of 138 randomized trials and nearly 150,000 participants in 2006 showed that selective COX-2 inhibitors were associated with a moderately increased risk of vascular events, which was mainly due to a two-fold increase in the risk of myocardial infarction. Times, and some traditional NSAIDs (such as diclofenac and ibuprofen, but not naproxen) in high-dose regimens are associated with similar increases in the risk of vascular events. It has been proposed that fish oils (for example, cod liver oil) are a reasonable alternative for the treatment of rheumatoid arthritis and other conditions because they provide lower cardiovascular risk than other therapies including NSAIDs.

Reference

1. Liu J.; et al. Prostaglandin endoperoxide H synthases: peroxidase hydroperoxide specificity and cyclooxygenase activation. The Journal of Biological Chemistry. 2007, 282 (25): 18233–44.