A mitochondria-targeted mass spectrometry probe to detect glyoxals: implications for diabetes

Li Pun, P. B. et al. (2014) A mitochondria-targeted mass spectrometry probe to detect glyoxals: implications for diabetes. Free Radical Biology and Medicine, 67, pp. 437-450. (doi:10.1016/j.freeradbiomed.2013.11.025) (PMID:24316194) (PMCID:PMC3978666)

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Abstract

The glycation of protein and nucleic acids that occurs as a consequence of hyperglycaemia disrupts cell function and contributes to many pathologies, including those associated with diabetes and aging. Intracellular glycation occurs following the generation of the reactive 1,2-dicarbonyls methylglyoxal and glyoxal and disruption to mitochondrial function is associated with hyperglycemia. However, the contribution of these reactive dicarbonyls to mitochondrial damage in pathology is unclear due to uncertainties about their levels within mitochondria in cells and in vivo. To address this we have developed a mitochondria-targeted reagent (MitoG) designed to assess the levels of mitochondrial dicarbonyls within cells. MitoG comprises a lipophilic triphenylphosphonium cationic function, which directs the molecules to mitochondria within cells and an o-phenylenediamine moiety that reacts with dicarbonyls to give distinctive and stable products. The extent of accumulation of these diagnostic heterocyclic products can be readily and sensitively quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), enabling changes to be determined. Using the MitoG-based analysis we assessed the formation of methylglyoxal and glyoxal in response to hyperglycaemia in cells in culture and in the Akita mouse model of diabetes in vivo. These findings indicated that the levels of methylglyoxal and glyoxal within mitochondria increase during hyperglycaemia in both cells and in vivo, suggesting that they can contribute to the pathological mitochondrial dysfunction that occurs in diabetes and aging.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hartley, Professor Richard and Gaddale Devanna, Dr Kishore Kumar
Authors: Li Pun, P. B., Logan, A., Darley-Usmar, V., Chacko, B., Johnson, M. S., Huang, G. W., Rogatti, S., Prime, T. A., Methner, C., Krieg, T., Fearnley, I. M., Larsen, L., Larsen, D. S., Menger, K. E., Collins, Y., James, A. M., Kumar, G.D. K., Hartley, R. C., Smith, R. A.J., and Murphy, M. P.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:Free Radical Biology and Medicine
Publisher:Elsevier, Inc.
ISSN:0891-5849
ISSN (Online):1873-4596
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Free Radical Biology and Medicine 67:437-450
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
553931Developing chemical mass spectrometry probes to assess the production of reactive oxygen species in vivoRichard HartleyBiotechnology and Biological Sciences Research Council (BBSRC)BB/I012826/1CHEM - CHEMISTRY