- A phase 1 trial of intravenous 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) in patients with advanced solid tumours.
- Horsley L, Cummings J, Middleton M, Ward T, Backen A, Clamp A, Dawson M, Farmer H, Fisher N, Halbert G, Halford S, Harris A, Hasan J, Hogg P, Kumaran G, Little R, Parker GJ, Potter P, Saunders M, Roberts C, Shaw D, Smith N, Smythe J, Taylor A, Turner H, Watson Y, Dive C, Jayson GC; Cancer Research UK Drug Development Office Phase I clinical trial.Author information Institute for Cancer Studies Christie Hospital NHS Foundation Trust, Wilmslow Road, Withington, Manchester, M20 4BX, UK.AbstractBACKGROUND: 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) is a water-soluble mitochondrial toxin that binds to adenine nucleotide translocase in the inner mitochondrial membrane, thereby targeting cell proliferation. This phase 1 study investigated safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and pharmacokinetics (PK) of GSAO as a daily 1-h infusion for 5 days a week for 2 weeks in every three. Pharmacodynamics of GSAO was evaluated by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and circulating markers of angiogenesis.
- Cancer chemotherapy and pharmacology.Cancer Chemother Pharmacol.2013 Dec;72(6):1343-52. doi: 10.1007/s00280-013-2320-9. Epub 2013 Oct 20.
- BACKGROUND: 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) is a water-soluble mitochondrial toxin that binds to adenine nucleotide translocase in the inner mitochondrial membrane, thereby targeting cell proliferation. This phase 1 study investigated safety, dose-limiting toxicities (DLTs)
- PMID 24141375
- Submaximal ADP-stimulated respiration is impaired in ZDF rats and recovered by resveratrol.
- Smith BK, Perry CG, Herbst EA, Ritchie IR, Beaudoin MS, Smith JC, Neufer PD, Wright DC, Holloway GP.Author information G. P. Holloway: Human Health and Nutritional Sciences, University of Guelph, 491 Gordon St., Guelph, ON, Canada, N1G 2W1. email@example.com.AbstractAbstract Mitochondrial dysfunction and reactive oxygen species (ROS) have been implicated in the aetiology of skeletal muscle insulin resistance, although there is considerable controversy regarding these concepts. Mitochondrial function has been traditionally assessed in the presence of saturating ADP, but ATP turnover and the resultant ADP is thought to limit respiration in vivo. Therefore, we investigated the potential link between submaximal ADP-stimulated respiration rates, ROS generation and skeletal muscle insulin sensitivity in a model of type 2 diabetes mellitus, the ZDF rat. Utilizing permeabilized muscle fibres we observed that submaximal ADP-stimulated respiration rates (250-2000 μm ADP) were lower in ZDF rats than in lean controls, which coincided with decreased adenine nucleotide translocase 2 (ANT2) protein content. This decrease in submaximal ADP-stimulated respiration occurred in the absence of a decrease in electron transport chain function. Treating ZDF rats with resveratrol improved skeletal muscle insulin resistance and this was associated with elevated submaximal ADP-stimulated respiration rates as well as an increase in ANT2 protein content. These results coincided with a greater ability of ADP to attenuate mitochondrial ROS emission and an improvement in cellular redox balance. Together, these data suggest that mitochondrial dysfunction is present in skeletal muscle insulin resistance when assessed at submaximal ADP concentrations and that ADP dynamics may influence skeletal muscle insulin sensitivity through alterations in the propensity for mitochondrial ROS emission.
- The Journal of physiology.J Physiol.2013 Dec 1;591(Pt 23):6089-101. doi: 10.1113/jphysiol.2013.259226. Epub 2013 Sep 30.
- Abstract Mitochondrial dysfunction and reactive oxygen species (ROS) have been implicated in the aetiology of skeletal muscle insulin resistance, although there is considerable controversy regarding these concepts. Mitochondrial function has been traditionally assessed in the presence of saturati
- PMID 24081154
- Dibenzofuran-induced mitochondrial dysfunction: Interaction with ANT carrier.
- Duarte FV, Gomes AP, Teodoro JS, Varela AT, Moreno AJ, Rolo AP, Palmeira CM.Author information CNC - Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Apartado 3046, 3001-401 Coimbra, Portugal. Electronic address: firstname.lastname@example.org.AbstractExposure to environmental pollutants such as dibenzofurans and furans is linked to the pathophysiology of several diseases. Dibenzofuran (DBF) is listed as a pollutant of concern due to its persistence in the environment, bioaccumulation and toxicity to humans, being associated with the development of lung diseases and cancers, due to its extremely toxic properties such as carcinogenic and teratogenic. Mitochondria play a key role in cellular homeostasis and keeping a proper energy supply for eukaryotic cells is essential in the fulfillment of the tissues energy-demand. Therefore, interference with mitochondrial function leads to cell death and organ failure. In this work, the effects of DBF on isolated rat liver mitochondria were analyzed. DBF exposure caused a markedly increase in the lag phase that follows depolarization induced by ADP, indicating an effect in the phosphorylative system. This was associated with a dose-dependent decrease in ATPase activity. Moreover, DBF also increased the threshold to the induction of the mitochondrial permeability transition (MPT) by calcium. Pretreatment of mitochondria with DBF also increased the concentration of carboxyatractyloside (CAT) necessary to abolish ADP phosphorylation and to induce the MPT, suggesting that DBF may interfere with mitochondria through an effect on the adenine nucleotide translocase (ANT). By co-immunoprecipitating ANT and Cyclophilin D (CypD) following MPT induction, we observed that in the presence of DBF, the ratio CypD/ANT was decreased. This demonstrates that DBF interferes with the ANT and so prevents CypD binding to the ANT, causing decreased phosphorylative capacity and inhibiting the MPT, which is also reflected by an increase in calcium retention capacity. Clarifying the role of pollutants in some mechanisms of toxicity, such as unbalance of bioenergetics status and mitochondrial function, may help to explain the progressive and chronic evolution of diseases derived from exposure to environmental pollutants.
- Toxicology in vitro : an international journal published in association with BIBRA.Toxicol In Vitro.2013 Dec;27(8):2160-8. doi: 10.1016/j.tiv.2013.08.009. Epub 2013 Sep 3.
- Exposure to environmental pollutants such as dibenzofurans and furans is linked to the pathophysiology of several diseases. Dibenzofuran (DBF) is listed as a pollutant of concern due to its persistence in the environment, bioaccumulation and toxicity to humans, being associated with the development
- PMID 24008156
- Bongkrekic acid as a selective activator of the peroxisome proliferator-activated receptor γ (PPARγ) isoform
- The Journal of Toxicological Sciences 40(2), 223-233, 2015
- NAID 130004904039
- GSK-3β, a Therapeutic Target for Cardiomyocyte Protection
- Circulation journal : official journal of the Japanese Circulation Society 73(7), 1184-1192, 2009-06-20
- NAID 10025932082
- OE-025 Cardioprotection by Erythropoietin is Associated with Translocation of Akt to Mitochondria and Its Interaction with the Adenine Nucleotide Translocase(Myocardial ischemia-reperfusion, basic/clinical-1 (IHD) OE5,Oral Presentation (English),The 70th Anniversary Annual Scientific Meeting of the Japanese Circulation Society)
- Circulation journal : official journal of the Japanese Circulation Society 70(Supplement_I), 154, 2006-03-01
- NAID 110005941392
- 2. Physiological Roles of Adenine Nucleotide Translocase Adenine nucleotide translocase (or adenine nucleotide translocator or Ant) is the most abundant protein in mitochondria, accounting for up to 10% of total ...
- 1. Curr Med Chem. 2003 Aug;10(16):1507-25. The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death. Halestrap AP(1), Brenner C. Author ...
|リンク元||「アデニンヌクレオチド輸送体」「アデニンヌクレオチド交換輸送体」「mitochondrial ADP-ATP translocase」「アデニンヌクレオチドトランスロカーゼ」|
- adenine nucleotide translocase
- adenine nucleotide translocase