The pleiotropic functions of aspirin: mechanisms of action

被引:41
作者
Amin, AR
Attur, MG
Pillinger, M
Abramson, SB
机构
[1] Hosp Joint Dis & Med Ctr, Dept Rheumatol, New York, NY 10003 USA
[2] NYU, Med Ctr, Dept Med, New York, NY 10016 USA
[3] NYU, Med Ctr, Kaplan Canc Ctr, Dept Pathol, New York, NY 10016 USA
关键词
aspirin; prostaglandin; COX; signal transduction; NF-kappa B; NOS;
D O I
10.1007/s000180050432
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent studies have suggested that aspirin and aspirin-like compounds have a variety of actions in addition to their well-studied ability to inhibit cyclooxygenases. These actions include inhibition of the uncoupling of oxidative phosphorylation, decreases in adenosine triphosphate stores, increases in extracellular adenosine, downregulation of the expression and activity of inducible nitric oxide synthetase, inhibition and/or stimulation of various mitogen-activated protein kinase activities and inhibition of nuclear factor binding kappa B site (NF-kappa B) activation. Moreover, aspirin-like compounds have recently been shown to have previously unappreciated clinical and biological effects, some apparently independent of cyclooxygenase. In this review we discuss the various mechanisms of action of aspirin-like compounds and their relevance to clinical disease and therapy.
引用
收藏
页码:305 / 312
页数:8
相关论文
共 63 条
[51]   Induction of an acetaminophen-sensitive cyclooxygenase with reduced sensitivity to nonsteroid antiinflammatory drugs [J].
Simmons, DL ;
Botting, RM ;
Robertson, PM ;
Madsen, ML ;
Vane, JR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (06) :3275-3280
[52]  
Smalley W E, 1997, Adv Pharmacol, V39, P1, DOI 10.1016/S1054-3589(08)60067-8
[53]   Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2 [J].
Smith, WL ;
Garavito, RM ;
DeWitt, DL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (52) :33157-33160
[54]   Aspirin-triggered 15-epi-lipoxin A(4) (LXA(4)) and LXA(4) stable analogues are potent inhibitors of Acute inflammation: Evidence for anti-inflammatory receptors [J].
Takano, T ;
Fiore, S ;
Maddox, JF ;
Brady, HR ;
Petasis, NA ;
Serhan, CN .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (09) :1693-1704
[55]   Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential [J].
Tsujii, M ;
Kawano, S ;
DuBois, RN .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (07) :3336-3340
[56]   Cyclooxygenase regulates angiogenesis induced by colon cancer cells [J].
Tsujii, M ;
Kawano, S ;
Tsuji, S ;
Sawaoka, H ;
Hori, M ;
DuBois, RN .
CELL, 1998, 93 (05) :705-716
[57]   PHARMACOLOGY - TOWARDS A BETTER ASPIRIN [J].
VANE, J .
NATURE, 1994, 367 (6460) :215-216
[58]   Cyclooxygenases 1 and 2 [J].
Vane, JR ;
Bakhle, YS ;
Botting, RM .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1998, 38 :97-120
[59]  
Vane JR, 1998, INFLAMM RES, V47, pS78
[60]  
WEISSMANN G, 1996, CECIL TXB MED, P111