|Title||The Mitochondria-Targeted Antioxidant MitoQ Modulates Mitochondrial Function and Endoplasmic Reticulum Stress in Pancreatic β Cells Exposed to Hyperglycaemia.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Escribano-Lopez, I, Bañuls, C, Diaz-Morales, N, Iannantuoni, F, Rovira-Llopis, S, Gomis, R, Rocha, M, Hernandez-Mijares, A, Murphy, MP, Víctor, VM|
|Journal||Cell Physiol Biochem|
|Keywords||Animals, Antioxidants, Cell Line, Tumor, Endoplasmic Reticulum Stress, Glucose, Hyperglycemia, Insulin-Secreting Cells, Mitochondria, Organophosphorus Compounds, Oxidative Stress, Rats, Reactive Oxygen Species, Signal Transduction, Ubiquinone|
BACKGROUND/AIMS: Mitochondria-targeted antioxidants such as mitoquinone (MitoQ) have demonstrated protective effects against oxidative damage in several diseases. The increase in reactive oxygen species (ROS) production during glucose metabolism in β cells can be exacerbated under hyperglycaemic conditions such as type 2 diabetes (T2D), thus contributing to β cell function impairment. In the present work, we aimed to evaluate the effect of MitoQ on insulin secretion, oxidative stress, endoplasmic reticulum (ER) stress and nuclear factor kappa B (NFκB) signalling in a pancreatic β cell line under normoglycaemic (NG, 11.1 mM glucose), hyperglycaemic (HG, 25 mM glucose) and lipidic (palmitic acid (PA), 0.5mM) conditions.
METHODS: We incubated the pancreatic β cell line INS-1E with or without MitoQ (0.5µM) under NG, HG and PA conditions. We then assessed the following parameters: glucose-induced insulin secretion, O₂ consumption (with a Clark-type electrode); mitochondrial function, oxidative stress parameters and calcium levels (by fluorescence microscopy); ER stress markers and NFκB-p65 protein levels (by western blotting).
RESULTS: MitoQ increased insulin secretion and prevented the enhancement of ROS production and O₂ consumption and decrease in GSH levels that are characteristic under HG conditions. MitoQ also reduced protein levels of ER stress markers (GRP78 and P-eIF2α) and the proinflammatory nuclear transcription factor NFκB-p65, both of which increased under HG. MitoQ did not significantly alter ER stress markers under lipidic conditions.
CONCLUSION: Our findings suggest that treatment with MitoQ modulates mitochondrial function, which in turn ameliorates endoplasmic reticulum stress and NFκB activation, thereby representing potential benefits for pancreatic β cell function.
|Alternate Journal||Cell. Physiol. Biochem.|
|Grant List||PI15/1424, PI16/1083, PI16/0301, CIBERehd CB06/04/0071, FI14/00125 / / Carlos III Health Institute / International |
PROMETEOII 2014/035 / / Regional Ministry Education of Valencian Community & European Regional Development Fund / International
UGP15-193, UGP-15-220, UGP-15-144 / / Foundation for the Promotion of Health and Biomedical Research in the Valencian Region / International
GRISOLIAP/2016/015 / / Generalitat Valenciana / International
FJCI-201525040 / / Spanish Ministry of Economy and Competitiveness / International
CES10/030, CPII16/00037 / / Ministry of Health of the Valencian Regional Government / International
MC_ U105663142 / / Medical Research Council UK / International
110159/Z/15/Z / / Wellcome Trust / United Kingdom