Why there are two cyclooxygenase isozymes

Abstract

Prostaglandins and their precursorsSince the discovery in 1991 of a second isoform of prostaglandin endoperoxide H synthase (PGHS, or cyclooxygenase), there has been considerable interest in the question of why two isoforms of this enzyme are necessary and what roles they might play. PGHS-1-deficient (1) and PGHS-2-deficient (2, 3) mice and isoform-specific inhibitors have been developed and used to investigate the physiological functions of PGHS-1 and PGHS-2. These studies suggest that there are processes in which each isozyme is uniquely involved (e.g., platelet aggregation for PGHS-1, ovulation for PGHS-2) and others in which both isozymes function coordinately (e.g., carcinogenesis, inflammation). There are also physiological events in which one PGHS isozyme normally functions but for which the other can compensate when the first is lacking (e.g., parturition and remodeling of the ductus arteriosus). Biochemical studies indicate that each isoform can function independently; namely, that there are distinct PGHS-1 and PGHS-2 prostanoid biosynthetic pathways. Thus, the unique physiological roles for each isozyme can be rationalized by what is known about the biochemistry of the enzymes.To facilitate discussion of the physiological functions of PGHS-1 and PGHS-2 and to point out those functions for which PGHS-1 and PGHS-2 can substitute for one another, we describe the following in sequence: (a) physiological processes that depend solely or primarily on PGHS-1, (b) physiological processes that depend solely or primarily on PGHS-2, and (c) processes in which both PGHS-1 and PGHS-2 are involved and act coordinately. We then summarize the biochemical evidence for distinct PGHS-1 and PGHS-2 biosynthetic pathways.

Protective effect of the G-765C COX-2 polymorphism on subclinical atherosclerosis and inflammatory markers in asymptomatic subjects with cardiovascular risk factors

“…COX-1 is a widely expressed constitutive enzyme that participates in tissue homeostasis. By contrast, COX-2, the inducible isoform, is expressed at low levels in most tissues but can be stimulated by LPS, growth factors and cytokines, such as TNF-a and interleukin-6 (IL-6) [3,4], being implicated in inflammatory processes, including atherosclerosis, rheumatoid diseases and carcinogenesis [5 -7]. A direct role for COX-2 in atherosclerosis can be inferred from studies showing significant expression in human atherosclerotic lesions [8][9][10], as well as COX-2-derived PGE 2 increase in subclinical atherosclerosis [11,12].…”

Wound Inflammation in Diabeticob/obMice

“…Besides the typical protein-type mediators, resident and invading cells in wound tissue communicate the initiation and resolution of the inflammatory process through the production of a variety of eicosanoids (19,20). Especially the prostaglandins (PGs), which are derived by enzymatically coupled biosynthetic pathways involving phospholipase A 2 , cyclooxygenase (COX), and PG synthase isoenzymes, are discussed to be central to these processes (19,20). In line with this, the COX-2 isoenzyme is rapidly induced under inflammatory conditions (21).…”

Hyperbaric oxygenation and the genic expression related to oxidative stress in the heart of mice during intestinal ischemia and reperfusion

“…is stimulated by inflammation; it is expressed by monocytes and macrophages that are activated by cytokines (IL-1 and IL-6), tumor necrosis factor (TNF), and other mediators at sites of inflammation 19,20 . The activity of HBO was dependent on the period of application, and it reduced oxidative stress in the HBO-IG and HBO-IRG in a manner that was suggestive of a probable anti-inflammatory and antioxidant effect during these periods.…”