Cyclooxygenase in biology and disease

Abstract

Cyclooxygenase (COX), the key enzyme required for the conversion of arachidonic acid to prostaglandins was first identified over 20 years ago. Drugs, like aspirin, that inhibit cyclooxygenase activity have been available to the public for about 100 years. In the past decade, however, more progress has been made in understanding the role of cyclooxygenase enzymes in biology and disease than at any other time in history. Two cyclooxygenase isoforms have been identified and are referred to as COX-1 and COX-2. Under many circumstances the COX-1 enzyme is produced constitutively (i.e., gastric mucosa) whereas COX-2 is inducible (i.e., sites of inflammation). Here, we summarize the current understanding of the role of cyclooxygenase-1 and -2 in different physiological situations and disease processes ranging from inflammation to cancer. We have attempted to include all of the most relevant material in the field, but due to the rapid progress in this area of research we apologize that certain recent findings may have been left out.

Oncogenic mutant of Gα12 stimulates cell proliferation through cycloxygenase-2 signaling pathway

“…Arachidonic acid is converted into other biologically active metabolites such as leukotrienes, lipoxins, prostaglandins and thromboxanes by di erent enzymes. The most important pathway is the sequential conversion of arachidonic acid into prostaglandin G 2 and prostaglandin H 2 by the enzyme prostaglandin endoperoxide synthase or cycloxygenase Dubois et al, 1998). There are two distinct isoforms of cycloxygenase known as cycloxygenase-1 (COX-1) and cycloxygenase-2 (COX-2).…”

“…There are two distinct isoforms of cycloxygenase known as cycloxygenase-1 (COX-1) and cycloxygenase-2 (COX-2). Cycloxygenase 1 is ubiquitously expressed in all the cell types and is involved in cellular`housekeeping' functions of various tissues and organs Dubois et al, 1998;Vane et al, 1998). In contrast, cycloxygenase-2 is an inducible enzyme whose induction and expression is dynamically regulated by growth factors, mitogens, tumor promoters, and physiological stress stimuli Dubois et al, 1998;Vane et al, 1998).…”

“…Cycloxygenase 1 is ubiquitously expressed in all the cell types and is involved in cellular`housekeeping' functions of various tissues and organs Dubois et al, 1998;Vane et al, 1998). In contrast, cycloxygenase-2 is an inducible enzyme whose induction and expression is dynamically regulated by growth factors, mitogens, tumor promoters, and physiological stress stimuli Dubois et al, 1998;Vane et al, 1998). The persistent activation of COX-2 has been shown to be associated with oncogenesis as well as the invasive potential of tumor cells (Dubois et al, 1998;Vane et al, 1998;Tsujii et al, 1997).…”

“…In contrast, cycloxygenase-2 is an inducible enzyme whose induction and expression is dynamically regulated by growth factors, mitogens, tumor promoters, and physiological stress stimuli Dubois et al, 1998;Vane et al, 1998). The persistent activation of COX-2 has been shown to be associated with oncogenesis as well as the invasive potential of tumor cells (Dubois et al, 1998;Vane et al, 1998;Tsujii et al, 1997). It is signi®cant to note that prostaglandin H 2 , the ®nal product of COX-2, acts as the immediate precursor for other prostaglandins and thromboxanes that are involved in various autocrine as well as paracrine control mechanisms .…”

Synthesis and characterization of novel oxazines and demonstration that they specifically target cyclooxygenase 2

“…The entanglement of cyclooxygenase (COX) as one of the key proinflammatory mediators has been well-demonstrated and found to be the good therapeutic target in treating several proinflammatory diseases. 7,8 COX1 and COX2 are the two isoforms of cyclooxygenase in which the former is constitutively expressed in normal tissues to maintain homeostasis and latter is renowned to express on cytokine induction in inflammatory cells. 9 Unfortunately, during chronic inflammation, COX2 is overexpressed which leads to exaggerated way of immune response and ultimately results in developing proinflammatory diseases.…”