Changes in mitochondrial carriers exhibit stress-specific signatures in INS-1E ß-cells exposed to glucose versus fatty acids
| Autor: | Pasquale Scarcia, Pascale Gaudet, Ferdinando Palmieri, Pierre Maechler, Ning Li, Dominique Duhamel, Thierry Brun |
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| Rok vydání: | 2013 |
| Předmět: |
Proteome
medicine.medical_treatment Apoptosis Mitochondrion medicine.disease_cause Oxidative Phosphorylation 0302 clinical medicine Insulin 0303 health sciences Multidisciplinary Fatty Acids Mitochondria Biochemistry Medicine Research Article medicine.drug Cell Survival Science 030209 endocrinology & metabolism Oxidative phosphorylation Carbohydrate metabolism Biology Cell Line Electron Transport Mitochondrial Proteins 03 medical and health sciences Downregulation and upregulation Stress Physiological Carnitine medicine Animals ddc:576 ddc:612 030304 developmental biology Gene Expression Profiling AMPK Biological Transport DNA Lipid Metabolism Rats Protein Subunits Glucose Energy Metabolism Transcriptome Oxidative stress Transcription Factors |
| Zdroj: | PLoS One PLoS ONE, Vol 8, Iss 12, p e82364 (2013) PloS one PLOS ONE, Vol. 8, No 12 (2013) P. e82364 PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0082364 |
| Popis: | Chronic exposure of β-cells to metabolic stresses impairs their function and potentially induces apoptosis. Mitochondria play a central role in coupling glucose metabolism to insulin secretion. However, little is known on mitochondrial responses to specific stresses; i.e. low versus high glucose, saturated versus unsaturated fatty acids, or oxidative stress. INS-1E cells were exposed for 3 days to 5.6 mM glucose, 25 mM glucose, 0.4 mM palmitate, and 0.4 mM oleate. Culture at standard 11.1 mM glucose served as no-stress control and transient oxidative stress (200 µM H2O2 for 10 min at day 0) served as positive stressful condition. Mito-array analyzed transcripts of 60 mitochondrion-associated genes with special focus on members of the Slc25 family. Transcripts of interest were evaluated at the protein level by immunoblotting. Bioinformatics analyzed the expression profiles to delineate comprehensive networks. Chronic exposure to the different metabolic stresses impaired glucose-stimulated insulin secretion; revealing glucotoxicity and lipo-dysfunction. Both saturated and unsaturated fatty acids increased expression of the carnitine/acylcarnitine carrier CAC, whereas the citrate carrier CIC and energy sensor SIRT1 were specifically upregulated by palmitate and oleate, respectively. High glucose upregulated CIC, the dicarboxylate carrier DIC and glutamate carrier GC1. Conversely, it reduced expression of energy sensors (AMPK, SIRT1, SIRT4), metabolic genes, transcription factor PDX1, and anti-apoptotic Bcl2. This was associated with caspase-3 cleavage and cell death. Expression levels of GC1 and SIRT4 exhibited positive and negative glucose dose-response, respectively. Expression profiles of energy sensors and mitochondrial carriers were selectively modified by the different conditions, exhibiting stress-specific signatures. |
| Databáze: | OpenAIRE |
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