Počet záznamů: 1
Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production
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SYSNO ASEP 0484402 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production Tvůrce(i) Pecinová, Alena (FGU-C) RID, ORCID, SAI
Drahota, Zdeněk (FGU-C) RID, ORCID
Kovalčíková, Jana (FGU-C)
Kovářová, Nikola (FGU-C) RID
Pecina, Petr (FGU-C) RID, ORCID
Alán, Lukáš (FGU-C) RID, ORCID
Zima, Michal (FGU-C)
Houštěk, Josef (FGU-C) RID, ORCID
Mráček, Tomáš (FGU-C) RID, ORCIDČíslo článku 7038603 Zdroj.dok. Oxidative Medicine and Cellular Longevity. - : Hindawi - ISSN 1942-0900
Roč. 2017, č. 2017 (2017)Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. US - Spojené státy americké Klíč. slova brown adipose tissue ; mitochondria ; respiratory chain oxidoreductases ; mitochondrial glycerophosphate dehydrogenase ; superoxide production ; biguanides ; metformin Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology CEP GA16-12726S GA ČR - Grantová agentura ČR LL1204 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora FGU-C - RVO:67985823 UT WOS 000407199100001 EID SCOPUS 85028431346 DOI 10.1155/2017/7038603 Anotace Metformin is widely prescribed as a first-choice antihyperglycemic drug for treatment of type 2 diabetes mellitus, and additionally recent epidemiological studies showed its utility in cancer therapy. Although it is in use since the 1970s, its molecular target, either for antihyperglycemic or antineoplastic action, remains elusive. The body of the research on metformin effect oscillates around mitochondrial metabolism, including the function of oxidative phosphorylation (OXPHOS) apparatus. In this study, we focused on direct inhibitory mechanism of biguanides (metformin and phenformin) on OXPHOS complexes and its functional impact, using the model of isolated brown adipose tissue mitochondria. We demonstrate that biguanides nonspecifically target the activities of all respiratory chain dehydrogenases (mitochondrial NADH, succinate, and glycerophosphate dehydrogenases), but only at very high concentrations (0.01 – 0.1 M) that highly exceed cellular concentrations observed during the treatment. In addition, these concentrations of biguanides also trigger burst of reactive oxygen species production which, in combination with pleiotropic OXPHOS inhibition, can be toxic for the organism. We conclude that the beneficial effect of biguanides should probably be associated with subtler mechanism, different from the generalized inhibition of the respiratory chain. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2018
Počet záznamů: 1