Carnosine protects stimulus-secretion coupling through prevention of protein carbonyl adduction events in cells under metabolic stress

Lavilla, C.J., Billacura, M.P., Hanna, K., Boocock, D.J. ORCID: 0000-0002-7333-3549, Coveney, C. ORCID: 0000-0001-7047-6408, Miles, A.K., Foulds, G.A. ORCID: 0000-0002-2053-7580, Murphy, A., Tan, A., Jackisch, L., Sayers, S.R., Caton, P.W., Doig, C.L. ORCID: 0000-0001-9694-4230, McTernan, P.G. ORCID: 0000-0001-9023-0261, Colombo, S.L. ORCID: 0000-0001-7360-986X, Sale, C. ORCID: 0000-0002-5816-4169 and Turner, M.D. ORCID: 0000-0001-7175-1053, 2021. Carnosine protects stimulus-secretion coupling through prevention of protein carbonyl adduction events in cells under metabolic stress. Free Radical Biology and Medicine. ISSN 0891-5849

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Abstract

Type 2 diabetes is characterized by failure to control glucose homeostasis, with numerous diabetic complications attributable to the resulting exposure of cells and tissues to chronic elevated concentrations of glucose and fatty acids. This, in part, results from formation of advanced glycation and advanced lipidation end-products that are able to modify protein, lipid, or DNA structure, and disrupt normal cellular function. Herein we used mass spectrometry to identify proteins modified by two such adduction events in serum of individuals with obesity, type 2 diabetes, and gestational diabetes, along with similar analyses of human and mouse skeletal muscle cells and mouse pancreatic islets exposed to glucolipotoxic stress. We also report that carnosine, a histidine containing dipeptide, prevented 65-90% of 4-hydroxynonenal and 3-nitrotyrosine adduction events, and that this in turn preserved mitochondrial function and protected stimulus-secretion coupling in cells exposed to metabolic stress. Carnosine therefore offers significant therapeutic potential against metabolic diseases.

Item Type: Journal article
Publication Title: Free Radical Biology and Medicine
Creators: Lavilla, C.J., Billacura, M.P., Hanna, K., Boocock, D.J., Coveney, C., Miles, A.K., Foulds, G.A., Murphy, A., Tan, A., Jackisch, L., Sayers, S.R., Caton, P.W., Doig, C.L., McTernan, P.G., Colombo, S.L., Sale, C. and Turner, M.D.
Publisher: Elsevier BV
Date: 27 August 2021
ISSN: 0891-5849
Identifiers:
NumberType
10.1016/j.freeradbiomed.2021.08.233DOI
1465512Other
Divisions: Schools > School of Science and Technology
Record created by: Laura Ward
Date Added: 02 Sep 2021 13:01
Last Modified: 02 Sep 2021 13:01
URI: http://irep.ntu.ac.uk/id/eprint/44103

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