Aspirin, Protein Transacetylation and Inhibition of Prostaglandin Synthetase in the Kidney

Caterson, Robyn J.; Duggin, Geoffrey G.; Horvath, John S.; Mohandas, Janardanan; Tiller, David J.

doi:10.1111/j.1476-5381.1978.tb08657.x

Cited by 18 publications

(7 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well known that the acetyl group of aspirin can acetylate several proteins other than COX ( Alfonso et al , 2009b ; Marimuthu et al , 2011 ; Bateman et al , 2013 ). Experiments with radiolabelled 3 H or 14 C aspirin demonstrated that aspirin acetylates several proteins in vitro and in vivo through a transacetylation reaction ( Hawkins et al , 1968 ; Caterson et al , 1978 ; Rainsford et al , 1983 ). Aspirin acetylates human serum albumin and fibrinogen in vitro and in vivo ( Hawkins et al , 1968 ; Bjornsson et al , 1989 ).…”

Section: Extra-cox Acetylation Targetsmentioning

confidence: 99%

Molecular targets of aspirin and cancer prevention

et al. 2014

View full text Add to dashboard Cite

Salicylates from plant sources have been used for centuries by different cultures to treat a variety of ailments such as inflammation, fever and pain. A chemical derivative of salicylic acid, aspirin, was synthesised and mass produced by the end of the 19th century and is one of the most widely used drugs in the world. Its cardioprotective properties are well established; however, recent evidence shows that it can also act as a chemopreventive agent. Its antithrombotic and anti-inflammatory actions occur through the inhibition of cyclooxygenases. The precise mechanisms leading to its anticancer effects are not clearly established, although multiple mechanisms affecting enzyme activity, transcription factors, cellular signalling and mitochondrial functions have been proposed. This review presents a brief account of the major COX-dependent and independent pathways described in connection with aspirin's anticancer effects. Aspirin's unique ability to acetylate biomolecules besides COX has not been thoroughly investigated nor have all the targets of its primary metabolite, salicylic acid been identified. Recent reports on the ability of aspirin to acetylate multiple cellular proteins warrant a comprehensive study to investigate the role of this posttranslational modification in its anticancer effects. In this review, we also raise the intriguing possibility that aspirin may interact and acetylate cellular molecules such as RNA, and metabolites such as CoA, leading to a change in their function. Research in this area will provide a greater understanding of the mechanisms of action of this drug.

show abstract

Section: Extra-cox Acetylation Targetsmentioning

confidence: 99%

Molecular targets of aspirin and cancer prevention

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Another study revealed that aspirin at micromolar concentrations acetylated rBC membrane peptides (30). elsewhere, aspirin was shown to acetylate renal cortical and medullary proteins after in vivo administration (15). This acetylation of proteins was rapid and increased the half-life of these proteins to more than 130 h. There is also a study that demonstrated the ability of aspirin to acetylate ubiquitin in vitro (31).…”

Section: Acetylation Of Other Proteins and Biomolecules By Aspirinmentioning

confidence: 87%

“…It is not at present clear how many of these lysine residues, besides K382, are acetylated by aspirin (35). In view of previous reports on the ability of aspirin to acetylate proteins through a transacetylation reaction (8,(12)(13)(14)(15), it is likely that aspirin targets multiple lysine residues on p53. Consistent with this notion, we observed that the incubation of purified recombinant p53 with low (100 µM) as well as high (2.5 mM) concentrations of aspirin resulted in p53 acetylation at lysine 382 (Fig.…”

Section: Acetylation Of P53 By Aspirinmentioning

confidence: 99%

“…Hydrolysis is enhanced during passage through the liver and other organs. Using radiolabeled 3 H or 14 C aspirin, it was shown that aspirin acetylates proteins in vitro and in vivo through a transacetylation reaction (8,(12)(13)(14)(15). However, detailed study on its ability to acetylate cellular proteins has not been carried out, as there is a lack of sensitive techniques.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Does aspirin acetylate multiple cellular proteins? (Review)

Bhat¹

2009

Mol Med Rep

View full text Add to dashboard Cite

Abstract. aspirin is a salicylate drug that is extensively used for its anti-inflammatory, antipyretic, analgesic and antithrombotic 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 3 H or 14 c 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.

show abstract

“…While aspirin's ability to acetylate and inhibit COX enzyme activity is well known (8,9), limited information is available as to whether it can acetylate other proteins and alter their functions (15,16). We recently demonstrated in MDA-MB-231 human breast cancer cells that one of the acetylation targets of aspirin is the tumor suppressor protein, p53 (17).…”

Section: Introductionmentioning

confidence: 99%

Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets

Marimuthu

Chivukula²,

Alfonso³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. Epidemiological and clinical observations provide consistent evidence that regular intake of aspirin may effectively inhibit the occurrence of epithelial tumors; however, the molecular mechanisms are not completely understood. In the present study, we determined the ability of aspirin to acetylate and posttranslationally modify cellular proteins in HCT-116 human colon cancer cells to understand the potential mechanisms by which it may exerts anti-cancer effects. Using anti-acetyl lysine antibodies, here we demonstrate that aspirin causes the acetylation of multiple proteins whose molecular weight ranged from 20 to 200 kDa. The identity of these proteins was determined, using immuno-affinity purification, mass spectrometry and immunoblotting. A total of 33 cellular proteins were potential targets of aspirin-mediated acetylation, while 16 were identified as common to both the control and aspirin-treated samples. These include enzymes of glycolytic pathway, cytoskeleton proteins, histones, ribosomal and mitochondrial proteins. The glycolytic enzymes which were identified include aldolase, glyceraldehyde-3-phosphate dehydrogenase, enolase, pyruvate kinase M2, and lactate dehydrogenase A and B chains. Immunoblotting experiment showed that aspirin also acetylated glucose-6-phosphate dehydrogenase and transketolase, both enzymes of pentose phosphate pathway involved in ribonucleotide biosynthesis. In vitro assays of these enzymes revealed that aspirin did not affect pyruvate kinase and lactate dehydrogenase activity; however, it decreased glucose 6 phosphate dehydrogenase activity. Similar results were also observed in HT-29 human colon cancer cells. Selective inhibition of glucose-6-phosphate dehydrogenase may represent an important mechanism by which aspirin may exert its anti-cancer effects through inhibition of ribonucleotide synthesis.

show abstract

Aspirin, Protein Transacetylation and Inhibition of Prostaglandin Synthetase in the Kidney

Cited by 18 publications

References 13 publications

Molecular targets of aspirin and cancer prevention

Molecular targets of aspirin and cancer prevention

Does aspirin acetylate multiple cellular proteins? (Review)

Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets

Contact Info

Product

Resources

About