Escribano-Lopez 2019 Cell Physiol Biochem
Escribano-Lopez I, BaΓ±uls 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 Ξ² Cells Exposed to Hyperglycaemia.. Cell Physiol Biochem 52(2):186-197. |
Escribano-Lopez I, BaΓ±uls 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 Ξ² cells can be exacerbated under hyperglycaemic conditions such as type 2 diabetes (T2D), thus contributing to Ξ² 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 (NFΞΊB) signalling in a pancreatic Ξ² 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 Ξ² cell line INS-1E with or without MitoQ (0.5Β΅M) under NG, HG and PA conditions. We then assessed the following parameters: glucose-induced insulin secretion, Oβ consumption (with a Clark-type electrode); mitochondrial function, oxidative stress parameters and calcium levels (by fluorescence microscopy); ER stress markers and NFΞΊB-p65 protein levels (by western blotting).
RESULTS: MitoQ increased insulin secretion and prevented the enhancement of ROS production and Oβ consumption and decrease in GSH levels that are characteristic under HG conditions. MitoQ also reduced protein levels of ER stress markers (GRP78 and P-eIF2Ξ±) and the proinflammatory nuclear transcription factor NFΞΊB-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 NFΞΊB activation, thereby representing potential benefits for pancreatic Ξ² cell function. β’ Keywords: ER stress; MitoQ; Mitochondrial dysfunction; Oxidative stress; Pancreatic Ξ² cells; Type 2 Diabetes β’ Bioblast editor: Sobotka O
Labels:
Pathology: Diabetes
Stress:Oxidative stress;RONS, Hypoxia