Potential of Mitochondria-Targeted Antioxidants to Prevent Oxidative Stress in Pancreatic beta-cells

0506716 - FGÚ 2020 RIV US eng J - Článek v odborném periodiku
Plecitá-Hlavatá, Lydie - Engstová, Hana - Ježek, Jan - Holendová, Blanka - Tauber, Jan - Petrásková, Lucie - Křen, Vladimír - Ježek, Petr
Potential of Mitochondria-Targeted Antioxidants to Prevent Oxidative Stress in Pancreatic beta-cells.
Oxidative Medicine and Cellular Longevity. Roč. 2019, č. 2019 (2019), č. článku 1826303. ISSN 1942-0900. E-ISSN 1942-0994
Grant CEP: GA ČR(CZ) GA16-06700S; GA ČR(CZ) GA17-01813S; GA ČR(CZ) GA18-00121S
Institucionální podpora: RVO:67985823 ; RVO:61388971
Klíčová slova: pancreatic beta cells * pancreatic islets * mitochondria- targeted antioxidants * oxidative stress * SkQ * S3QEL * S1QEL
Obor OECD: Cell biology; Physiology (including cytology) (MBU-M)
Impakt faktor: 5.076, rok: 2019
Způsob publikování: Open access
https://doi.org/10.1155/2019/1826303

Pancreatic beta-cells are vulnerable to oxidative stress due to their low content of redox buffers, such as glutathione, but possess a rich content of thioredoxin, peroxiredoxin, and other proteins capable of redox relay, transferring redox signaling. Consequently, it may be predicted that cytosolic antioxidants could interfere with the cytosolic redox signaling and should not be recommended for any potential therapy. In contrast, mitochondrial matrix-targeted antioxidants could prevent the primary oxidative stress arising from the primary superoxide sources within the mitochondrial matrix, such as at the flavin (I-F) and ubiquinone (I-Q) sites of superoxide formation within respiratory chain complex I and the outer ubiquinone site (IIIQ) of complex III. Therefore, using time-resolved confocal fluorescence monitoring with MitoSOX Red, we investigated various effects of mitochondria-targeted antioxidants in model pancreatic beta-cells (insulinoma INS-1E cells) and pancreatic islets. Both SkQ1 (a mitochondria-targeted plastoquinone) and a suppressor of complex III site Q electron leak (S3QEL) prevented superoxide production released to the mitochondrial matrix in INS-1E cells with stimulatory glucose, where SkQ1 also exhibited an antioxidant role for UCP2-silenced cells. SkQ1 acted similarly at nonstimulatory glucose but not in UCP2-silenced cells. Thus, UCP2 can facilitate the antioxidant mechanism based on SkQ1(+) fatty acid anion(-) pairing. The elevated superoxide formation induced by antimycin A was largely prevented by S3QEL, and that induced by rotenone was decreased by SkQ1 and S3QEL and slightly by S1QEL, acting at complex I site Q. Similar results were obtained with the MitoB probe, for the LC-MS-based assessment of the 4 hr accumulation of reactive oxygen species within the mitochondrial matrix but for isolated pancreatic islets. For 2 hr INS-1E incubations, some samples were influenced by the cell death during the experiment. Due to the frequent dependency of antioxidant effects on metabolic modes, we suggest a potential use of mitochondria-targeted antioxidants for the treatment of prediabetic states after cautious nutrition-controlled tests. Their targeted delivery might eventually attenuate the vicious spiral leading to type 2 diabetes.
Trvalý link: http://hdl.handle.net/11104/0297909