Advances in the pharmacology of cyclooxygenase

17 3 2005 6 Chinese Bulletin of Life Sciences Vol. 17, No.3 Jun., 2005 1004-0374(2005)03-0231-05 201203 (cyclooxygenase COX) (prostaglandins PGs) COX COX-1 COX-2 COX-1 COX-2 Q55 A Advances in the pharmacology of cyclooxygenase ZHANG Wei-Yu, ZHU Xing-Zu* (Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of CAS, Shanghai 201203, China) Abstract: Cyclooxygenase (COX), a rate-limited enzyme in arachidonic acid metabolic pathways, can catalyse the synthesis of cyclic endoperoxides from arachidonic acid to form prostaglandins (PGs). Two cyclooxygenase isoforms have been identified and referred to as constitutive COX-1 and inducible COX-2. According to a popular hypothesis, COX-1 generates good prostaglandins for physiological housekeeping functions, while COX-2 forms the bad prostaglandins responsible for inflammatory symptoms. However, recent data show that the biological functions of prostanoids formed by the two enzymes are much more complex and interrelated than previously appreciated. The objective of the article is to provide an overview of recent developments in the field about the role of COX in various diseases, and to discuss the feasibility as a potential target for therapeutic treatment. Key words: cyclooxygenase; prostaglandins; inflammation; neurodegenerative disease; cardiovascular disease; cancer; non-steroidal anti-inflammatory drugs (COX)(prostaglandins, PGs) (thromboxane, TX) COX (1) G 2 (PGG 2 ); (2) PGG 2 H 2 (PGH 2 ) COX COX-1 COX-2 COX-1 COX-2 COX-1 2005-01-13 2005-02-21 No. 04DZ14005 (1973 ) (1946 ) *

232 COX-2 (nonsteroidal anti-inflammatory drugs, NSAIDs) COX NSAIDs COX-1 COX-2 COX-1 NSAIDs NSAIDs COX-2 celecoxib rofecoxib COX-1 COX-2 [1] COX 1 COX COX-2 COX-2 COX-2 [2] celecoxib COX-1 [3] COX-1 [4 8] COX-2 E 2 (PGE 2 ) COX-1 COX-2 COX-1 COX-2 COX-1 COX COX-2 [9] COX-2 2 h 48 h 2 h 3.5 PGE 2 48 h 15- deoxy-d 12 14 -PGJ 2 COX-2 2 h 48 h COX-2 2 COX COX-1 PG (LPS) -1(IL-1) COX-2 PGE 2 [10 11] COX-2 NSAIDs (Alzheimer s disease, AD) [12] COX-2 [13] AD COX-2 β- (β-amyloid, Aβ) SH-SY5Y COX-2 [14] 1- -4- -1 2 3 6- (1-methyl- 4-phenyl-1,2,3,6- tetrahydropyridine, MPTP) COX-2 JNK/c-Jun [15] COX-2 COX-2 (reactive oxygenase species, ROS) [16] ROS (Parkinson s disease, PD) ROS COX-2 D 2 (PGD 2 ) J 2 (PGJ 2 ) COX-2 [17] PGJ 2

233 [18] COX-2 COX-2 COX-2 MPTP PD [19] COX NSAIDs AD [20] NSAIDs (ibuprofen) (indomethacin) Aβ42 [21] COX PGE 2 Aβ NSAIDs γ- (γ-secretase) [22] COX-2 3 COX (atherosclerosis) COX-1 A 2 (TXA 2 ) COX-2 I 2 (PGI 2 ) [23] COX-1 TXA 2 PGI 2 COX-2 PGI 2 TXA 2 COX-2 PGI 2 PGE 2 [24] Baker [25] / COX-2 COX-2 COX-2 apoe [26] [27] (LDL) X (LXR) COX-2 [28~29] COX-2 COX-2 TXA 2 COX-2 [30] 4 COX COX-2 COX-1 COX-2 mrna [31] C(PKC) Ras COX-2 AP-1 NF-IL6 NF-κB NFAT PEA3 COX-2 TATA TATA (TATA box) p53 COX-2 [32] p53 COX-2 COX-2 COX-2 COX-2 mrna 3' AU (AU-enriched elements) COX-2 mrna COX-2 mrna COX-2 mrna [31] COX-2 COX-2 COX-2 [32] COX-2 [33] COX-2 (knock out) COX-2 COX-1 [34~35] COX-2 COX-2 COX-2 COX-2

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