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Adipocyte protein modification by Krebs cycle intermediates and fumarate ester-derived succination

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Abstract

Protein succination, the non-enzymatic modification of cysteine residues by fumarate, is distinguishable from succinylation, an enzymatic reaction forming an amide bond between lysine residues and succinyl-CoA. Treatment of adipocytes with 30 mM glucose significantly increases protein succination with only a small change in succinylation. Protein succination may be significantly increased intracellularly after treatment with fumaric acid esters, however, the ester must be removed by saponification to permit 2SC-antibody detection of the fumarate adduct.

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Fig. 1
Fig. 2

Abbreviations

2SC:

S-(2-succino)cysteine

MMF:

Monomethylfumarate

DMF:

Dimethylfumarate

GSH:

Glutathione

Keap1:

Kelch-like ECH-associated protein 1

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Acknowledgments

The authors thank Professor John Baynes at the University of South Carolina for helpful discussion. The authors thank Dr Zhongi Cheng (PTM Biolabs) for providing anti-succinyllysine antibody. This work was supported by the Magellan Scholarship Award from the University of South Carolina Undergraduate Research Office, the American Diabetes Association Junior Faculty Award 1-11-JF-13, and the National Institute of Diabetes and Digestive and Kidney Diseases DK-19971.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Road, VA Bldg 1, 3rd Floor, D16, Columbia, SC, 29208, USA

    Allison M. Manuel & Norma Frizzell

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  1. Allison M. Manuel
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  2. Norma Frizzell
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Correspondence to Norma Frizzell.

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Manuel, A.M., Frizzell, N. Adipocyte protein modification by Krebs cycle intermediates and fumarate ester-derived succination. Amino Acids 45, 1243–1247 (2013). https://doi.org/10.1007/s00726-013-1568-z

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  • DOI: https://doi.org/10.1007/s00726-013-1568-z

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