Escribano-Lopez 2019 Cell Physiol Biochem
| Escribano-Lopez I, Bañuls C, Diaz-Morales N, Iannantuoni F, Rovira-Llopis S, Gomis R, Rocha M, Hernandez-Mijares A, Murphy MP, Victor VM (2019) The Mitochondria-Targeted Antioxidant MitoQ Modulates Mitochondrial Function and Endoplasmic Reticulum Stress in Pancreatic β Cells Exposed to Hyperglycaemia.. Cell Physiol Biochem 52(2):186-197. |
Escribano-Lopez I, Bañuls C, Diaz-Morales N, Iannantuoni F, Rovira-Llopis S, Gomis R, Rocha M, Hernandez-Mijares A, Murphy MP, Victor VM (2019) Cell Physiol Biochem
Abstract: 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. • Keywords: ER stress; MitoQ; Mitochondrial dysfunction; Oxidative stress; Pancreatic β cells; Type 2 Diabetes • Bioblast editor: Sobotka O
Labels:
Pathology: Diabetes
Stress:Oxidative stress;RONS, Hypoxia
