Does aspirin acetylate multiple cellular proteins? (Review)

被引:48
作者
Alfonso, Lloyd F.
Srivenugopal, Kalkunte S.
Bhat, G. Jayarama [1 ]
机构
[1] Texas Tech Univ, Hlth Sci Ctr, Dept Pharmaceut Sci, Amarillo, TX 79106 USA
关键词
aspirin; acetylation; cyclooxygenases; albumin; platelets; fibrinogen; hemoglobin; p53; HUMAN SERUM-ALBUMIN; KAPPA-B ACTIVATION; ACETYLSALICYLIC-ACID; PROSTAGLANDIN SYNTHETASE; CANCER CELLS; HEMOGLOBIN; MECHANISM; APOPTOSIS; INHIBITION; CRYSTALLINS;
D O I
10.3892/mmr_00000132
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Aspirin is a salicylate drug that is extensively used for its anti-inflammatory, antipyretic, analgesic and anti-thrombotic effects. More recently, it has been shown to decrease the incidence of cancers of epithelial origin. In most cases, aspirin is relatively safe. However, it does cause a host of adverse effects and toxicities, including gastrointestinal bleeding, ulcerations, nephrotoxicity and hypersensitivity reactions. Although the inhibition of cyclooxygenases by aspirin, which leads to its anti-inflammatory/analgesic properties, has been well studied, the mechanisms involved in its chemopreventive effects as well as some of its adverse effects are as yet ill-defined. Studies over the past decades suggest that, besides cyclooxygenases, aspirin acetylates other cellular proteins. These studies used radiolabeled H-3 or C-14 aspirin, the only approach used to date for the detection of proteins acetylated by aspirin. In a recent study using protein-specific anti-acetyl lysine antibodies and immunological methods, we demonstrated the ability of aspirin to acetylate the tumor suppressor protein p53. In this review, we present current research from the literature on the aspirin-induced acetylation of proteins. We also describe an immunological approach to detecting acetylated proteins in aspirin-treated cells, and demonstrate that multiple proteins are acetylated. Since post-translational modification of proteins, such as acetylation, may lead to the alteration of their function, it is possible that some of the hitherto unexplained beneficial or adverse effects of aspirin could occur as a result of these modifications. The identification of these novel acetylation targets of aspirin represents a new area for investigation.
引用
收藏
页码:533 / 537
页数:5
相关论文
共 42 条
[1]   Aspirin inhibits camptothecin-induced p21CIP1 levels and potentiates apoptosis in human breast cancer cells [J].
Alfonso, Lloyd F. ;
Srivenugopal, Kalkunte S. ;
Arumugam, Thiruma V. ;
Abbruscato, Thomas J. ;
Weidanz, Jon A. ;
Bhat, G. Jayarama .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2009, 34 (03) :597-608
[2]  
BJORNSSON TD, 1989, J PHARMACOL EXP THER, V250, P154
[3]   Post-translational modification of p53 in tumorigenesis [J].
Bode, AM ;
Dong, ZG .
NATURE REVIEWS CANCER, 2004, 4 (10) :793-805
[4]   ACETYLATION OF HEMOGLOBIN BY ASPIRIN - INVITRO AND INVIVO [J].
BRIDGES, KR ;
SCHMIDT, GJ ;
JENSEN, M ;
CERAMI, A ;
BUNN, HF .
JOURNAL OF CLINICAL INVESTIGATION, 1975, 56 (01) :201-207
[5]   ASPIRIN, PROTEIN TRANSACETYLATION AND INHIBITION OF PROSTAGLANDIN SYNTHETASE IN KIDNEY [J].
CATERSON, RJ ;
DUGGIN, GG ;
HORVATH, J ;
MOHANDAS, J ;
TILLER, D .
BRITISH JOURNAL OF PHARMACOLOGY, 1978, 64 (03) :353-358
[6]   Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer [J].
Chan, AT ;
Giovannucci, EL ;
Meyerhardt, JA ;
Schernhammer, ES ;
Curhan, GC ;
Fuchs, CS .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2005, 294 (08) :914-923
[7]   GLYCATION OF HUMAN LENS CRYSTALLINS - EFFECT OF AGE AND ASPIRIN TREATMENT [J].
CHERIAN, M ;
ABRAHAM, EC .
OPHTHALMIC RESEARCH, 1993, 25 (06) :349-354
[8]  
De Furia F G, 1973, Proc Natl Acad Sci U S A, V70, P3707
[9]   Aspirin induces apoptosis through the inhibition of proteasome function [J].
Dikshit, Priyanka ;
Chatterjee, Mou ;
Goswami, Anand ;
Mishra, Amit ;
Jana, Nihar Ranjan .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (39) :29228-29235
[10]   ACETYLATION OF ERYTHROCYTIC MEMBRANE PEPTIDES BY ASPIRIN [J].
GREEN, FA ;
JUNG, CY .
TRANSFUSION, 1981, 21 (01) :55-58