title: Inhibition of mitochondrial glycerol-3-phosphate dehydrogenase by α-tocopheryl succinate.
abstract: α-Tocopheryl succinate (TOS), a redox-silent analogue of vitamin E, suppresses cell growth in a number of clinical and experimental cancers, inhibits mitochondrial succinate dehydrogenase (SDH) and activates reactive oxygen species (ROS) generation. The aim of this study was to test whether TOS also inhibits glycerol-3-phosphate dehydrogenase (mGPDH), another flavoprotein-dependent enzyme of the mitochondrial respiratory chain because there are differences between electron transfer pathway from SDH and mGPDH to coenzyme Q pool. For our experiments brown adipose tissue mitochondria with high expression of mGPDH were used. Our data showed that inhibition of glycerol-3-phosphate (GP)-dependent oxygen consumption by TOS was more pronounced than the succinate (SUC)-dependent one (50% inhibition was reached at 10 μmol/l TOS vs. 80 μmol/l TOS, respectively). A comparison of the inhibitory effect of TOS on GP-oxidase, GP-cytochrome c oxidoreductase and GP-dehydrogenase activities showed that TOS directly interacts with the dehydrogenase. After TOS application the GP-dependent generation of ROS was highly depressed. It may thus be concluded that TOS-induced inhibition of mGPDH is more pronounced than TOS-induced inhibition of SDH and that the inhibitory effect of TOS for both substrates is exerted at different locations of the particular dehydrogenases. Our data indicate that the inhibition of mGPDH activity could also play a role in TOS-induced growth suppression in neoplastic cells.
authors: Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, Prague 14220, Czech Republic. Electronic address: rauchova@biomed.cas.cz.
authors: Hana
authors: H
authors: Rauchová
authors: Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, Prague 14220, Czech Republic.
authors: Martina
authors: M
authors: Vokurková
authors: Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, Prague 14220, Czech Republic.
authors: Zdeněk
authors: Z
authors: Drahota
mesh_terms: D002001:Adipose Tissue, Brown / Q000201:enzymology; D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D006224:Cricetinae; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005993:Glycerolphosphate Dehydrogenase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D010101:Oxygen Consumption / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D024502:alpha-Tocopherol / Q000008:administration & dosage*
chemical_list: D017382:Reactive Oxygen Species; D005993:Glycerolphosphate Dehydrogenase; D024502:alpha-Tocopherol
keywords: Brown adipose tissue mitochondria; Glycerol-3-phosphate; Oxygen consumption; Reactive oxygen species; Succinate