Inhibition of glycation of albumin and hemoglobin by acetylation in vitro and in vivo

Marc Rendell, Julia Nierenberg, Carol Brannan, J. L. Valentine, P. M. Stephen, Steven Dodds, Preston Mercer, Paul K. Smith, Joseph Walder

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Abstract

Aspirin (acetylsalicyclic acid or ASA) is known to inhibit glycosylation (glycation) of albumin in vitro. The mechanism has been presumed to be acetylation, but this has never been validated. The new affinity aminophenylboronic acid procedure for determination of glycosylated albumin was used to demonstrate inhibition of glycosylation by aspirin. ASA, but not salicylic acid, inhibited glycation. The inhibition of glycation by equimolar acetic anhydride was greater than that by ASA. Pretreatment of albumin with ASA in the absence of glucose demonstrated that inhibition was extremely rapid, occurring in a matter of minutes. However, the inhibition by ASA could not be prevented by massive acceleration of glycation induced by borohydride reduction. Glycation of hemoglobin was also inhibited by ASA, but the dose requirement was considerably higher. Various analogues of ASA were evaluated for inhibition of glycation. Only acetyl-5-ethylsalicylic acid was more effective than ASA in inhibiting albumin glycation. None of these agents was more potent than ASA in inhibiting glycation of hemoglobin. ASA was fed to diabetic rats in a long-term experiment. Glycohemoglobin and glycoalbumin levels were decreased by ASA administration. We conclude that ASA inhibits glycation by a very rapid acetylation process. This process is apparently quite selective in terms of the protein involved, presumably because of the local environment of affected lysine groups. The phenomenon can be produced in vivo by administration of ASA.

Original languageEnglish (US)
Pages (from-to)277-285
Number of pages9
JournalThe Journal of Laboratory and Clinical Medicine
Volume108
Issue number4
StatePublished - Oct 1986

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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    Rendell, M., Nierenberg, J., Brannan, C., Valentine, J. L., Stephen, P. M., Dodds, S., Mercer, P., Smith, P. K., & Walder, J. (1986). Inhibition of glycation of albumin and hemoglobin by acetylation in vitro and in vivo. The Journal of Laboratory and Clinical Medicine, 108(4), 277-285.