COX2 cyclooxygenase

CYP5 synthesizes thromboxane A2, a fatty acid in the arachidonic acid cascade that causes platelet aggregation. Aspirin prevents platelet aggregation because it blocks the cyclooxygenases COX1 and COX2 which catalyze the initial step of the biotransformation of arachidonic acid to thromboxane and prostaglandins. 

Despite the clinical evidence implicating the involvement of inflammatory processes in the pathology of AD, the mechanisms behind the accumulation of inflammatory mediators is complex. Nevertheless, it would appear that cyclooxygenase 2 (COX2) plays a crucial role. It is known that COX2 activity is elevated in the brain of the patient with AD and that there is an increased expression of COX2 mRNA in the frontal cortex of such patients. Furthermore, the severity of the symptoms correlates with both the COX2 activity and the increased expression of Ab. 

Figure 14.2 The two isoforms of cyclooxygenase (COX1 and COX2) produce identical products but different effects. COX1 is constitutively produced in many tissues, such as the kidney and the gastrointestinal tract, whereas COX2 is an inducible enzyme produced primarily in inflammatory settings. The two isoforms are involved in production of eicosanoids that have various roles. PG, prostaglandin ...

Structures of cyclooxygenase-2 (COX2) selective inhibitors. (A) Celecoxib and (B) Rofecoxib. 

This concept has led to market isoenzyme selective inhibitors, that is, monoamine oxidase (MAO) inhibitors (moclobemide for MAO-A as an antidepressive drug, selegiline for MAO-B in Parkinson disease), selective inhibitors for various cyclic nucleotide phosphodiesterases (sildenafil for PDE5), and selective cyclooxygenase inhibitors (celecoxib for cox2). 

Most research has focused on the ability of salicylates to suppress the synthesis of prostaglandins, hormones thought to play an integral role in pain, inflammation, and fever. Two specific enzymes, cyclooxygenase 1 and 2 (COXl and COX2), are considered to be predominant in this process. COXl occurs in platelets, blood vessels, and other organs COX2 acts primarily in inflamed tissue. 

The two main cyclooxygenase enzymes, the constitutive COXl and inflammation-induced COX2, are primarily involved in the conversion of ARA to prostaglandins and related eicosanoids. However, in the presence of aspirin these enzymes behave differently. Although aspirin acetylates the active site serine of both COXl and COX2, only COXl becomes completely inhibited by aspirin. Despite being unable... 

Both cyclooxygenase-2 and inducible nitric oxide synthase were expressed in 30 human mesothelioma tissues but were not detectable in non-reactive mesothelial tissues from the same individuals (Marrogi et al. 2000). In vitro exposure of human mesothelioma cell lines to the COX2 inhibitor, NS398, revealed dose- and time-dependent antiproliferative activity, whereas the NOS2 inhibitor, 1400 W, had no detectable inhibitory effect. 

Cyclooxygenase 2 (COX2) Immune, CV Anti-inflammatory, anti-mitogenic, hypertension... 

Cyclooxygenase type 2 (COX2) is an important mediator of inflammation involved in prostaglandin synthesis (Fig. 17.3). Arachidonic acid, released from... 

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