Carnosine protects stimulus-secretion coupling through prevention of protein carbonyl adduction events in cells under metabolic stress
| Autor: | Mark D. Turner, Merell P. Billacura, Amanda K. Miles, Sophie R. Sayers, Charlie Jr Lavilla, David J. Boocock, Alice Murphy, Clare Coveney, Philip G. McTernan, Laura Jackisch, Paul W. Caton, Craig Doig, Sergio L. Colombo, Katie Hanna, Craig Sale, Arnold Tan, Gemma A. Foulds |
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| Rok vydání: | 2021 |
| Předmět: |
Glycation End Products
Advanced medicine.medical_specialty Carnosine Lipid-anchored protein Type 2 diabetes Biochemistry Diabetes Complications Protein Carbonylation chemistry.chemical_compound Mice Glycation Physiology (medical) Internal medicine medicine Glucose homeostasis Animals Chemistry Pancreatic islets Skeletal muscle medicine.disease Gestational diabetes Oxidative Stress Endocrinology medicine.anatomical_structure Diabetes Mellitus Type 2 |
| Zdroj: | Free radical biologymedicine. 175 |
| ISSN: | 1873-4596 0891-5849 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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