Persistent mitoKATP Activation Is Involved in the Isoflurane-induced Cytotoxicity
Tóm tắt
Isoflurane exposure induces apoptosis in cultured cells and in the developing brain, while the underlying mechanism remains largely unclarified. This study was designed to determine whether the disruption of mitoKATP-mediated ATP balance was involved in the cytotoxicity of isoflurane. Human neuroglioma cells U251 and 7-day-old mice were treated with isoflurane. A specific mitoKATP antagonist 5-HD was used, and the cellular ATP levels, NAD+/NADH ratios, and mitochondrial transmembrane potential (ΔΨm) were measured. Our data showed that the blockage of mitoKATP by 5-HD mitigated the isoflurane-induced ΔΨm disruption, reactive oxygen species (ROS) accumulation, and apoptosis in U251 cells. Moreover, we found that the toxic effect of isoflurane was not observed in the first 2-h exposure; instead, the cellular ATP levels and NAD+/NADH ratios were markedly increased. The reduction of ATP levels and NAD+/NADH ratios was only detected after this initial phase. This dynamical effect of isoflurane was blocked by 5-HD. In contrast, a ROS scavenger NAC sustained the isoflurane-induced ATP elevation. Similar results were observed in animal studies. And again, 5-HD attenuated isoflurane-induced cognitive disorders in the Intellicage test, a system that assesses place learning behavior in a social environment. Our study uncovered a potential mechanism underlying isoflurane’s toxicity with a therapeutic future.
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citation_journal_title=Nature; citation_title=ATP-sensitive K+ channel in the mitochondrial inner membrane; citation_author=I Inoue, H Nagase, K Kishi, T Higuti; citation_volume=352; citation_issue=6332; citation_publication_date=1991; citation_pages=244-247; citation_doi=10.1038/352244a0; citation_id=CR1
citation_journal_title=J Biol Chem; citation_title=Reconstitution and partial purification of the glibenclamide-sensitive, ATP-dependent K+ channel from rat liver and beef heart mitochondria; citation_author=P Paucek, G Mironova, F Mahdi, AD Beavis, G Woldegiorgis, KD Garlid; citation_volume=267; citation_issue=36; citation_publication_date=1992; citation_pages=26062-26069; citation_id=CR2
citation_journal_title=J Pharmacol Exp Ther; citation_title=Role of an ATP-sensitive potassium channel opener, YM934, in mitochondrial energy production in ischemic/reperfused heart; citation_author=K Tanonaka, T Taguchi, M Koshimizu, T Ando, T Morinaka, T Yogo, F Konishi, S Takeo; citation_volume=291; citation_issue=2; citation_publication_date=1999; citation_pages=710-716; citation_id=CR3
citation_journal_title=Am J Physiol Heart Circ Physiol; citation_title=Bioenergetic consequences of opening the ATP-sensitive K(+) channel of heart mitochondria; citation_author=AJ Kowaltowski, S Seetharaman, P Paucek, KD Garlid; citation_volume=280; citation_issue=2; citation_publication_date=2001; citation_pages=H649-657; citation_id=CR4
citation_journal_title=J Bioenerg Biomembr; citation_title=ATP-regulated K+ channel in mitochondria: pharmacology and function; citation_author=A Szewczyk, A Czyz, G Wojcik, L Wojtczak, MJ Nalecz; citation_volume=28; citation_issue=2; citation_publication_date=1996; citation_pages=147-152; citation_doi=10.1007/BF02110645; citation_id=CR5
citation_journal_title=Acta Biochim Pol; citation_title=The ATP-regulated K+ channel in mitochondria: five years after its discovery; citation_author=A Szewczyk; citation_volume=43; citation_issue=4; citation_publication_date=1996; citation_pages=713-719; citation_id=CR6
citation_journal_title=Anesthesiology; citation_title=Inhalation anesthetics induce apoptosis in normal peripheral lymphocytes in vitro; citation_author=H Matsuoka, S Kurosawa, T Horinouchi, M Kato, Y Hashimoto; citation_volume=95; citation_issue=6; citation_publication_date=2001; citation_pages=1467-1472; citation_doi=10.1097/00000542-200112000-00028; citation_id=CR7
citation_journal_title=J Clin Anesth; citation_title=Isoflurane hepatitis-induced liver failure: a case report; citation_author=LJ Peiris, A Agrawal, JE Morris, PS Basnyat; citation_volume=24; citation_issue=6; citation_publication_date=2012; citation_pages=477-479; citation_doi=10.1016/j.jclinane.2011.12.004; citation_id=CR8
citation_journal_title=Anesthesiology; citation_title=Comparison of the neuroapoptotic properties of equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in neonatal mice; citation_author=GK Istaphanous, J Howard, X Nan, EA Hughes, JC McCann, JJ McAuliffe, SC Danzer, AW Loepke; citation_volume=114; citation_issue=3; citation_publication_date=2011; citation_pages=578-587; citation_doi=10.1097/ALN.0b013e3182084a70; citation_id=CR9
citation_journal_title=J Neurosci; citation_title=Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits; citation_author=V Jevtovic-Todorovic, RE Hartman, Y Izumi, ND Benshoff, K Dikranian, CF Zorumski, JW Olney, DF Wozniak; citation_volume=23; citation_issue=3; citation_publication_date=2003; citation_pages=876-882; citation_id=CR10
citation_journal_title=Anesthesiology; citation_title=Isoflurane causes greater neurodegeneration than an equivalent exposure of sevoflurane in the developing brain of neonatal mice; citation_author=G Liang, C Ward, J Peng, Y Zhao, B Huang, H Wei; citation_volume=112; citation_issue=6; citation_publication_date=2010; citation_pages=1325-1334; citation_doi=10.1097/ALN.0b013e3181d94da5; citation_id=CR11
citation_journal_title=Neuroscience; citation_title=Anesthesia induces neuronal cell death in the developing rat brain via the intrinsic and extrinsic apoptotic pathways; citation_author=JH Yon, J Daniel-Johnson, LB Carter, V Jevtovic-Todorovic; citation_volume=135; citation_issue=3; citation_publication_date=2005; citation_pages=815-827; citation_doi=10.1016/j.neuroscience.2005.03.064; citation_id=CR12
citation_journal_title=N Engl J Med; citation_title=Defining safe use of anesthesia in children; citation_author=B Rappaport, RD Mellon, A Simone, J Woodcock; citation_volume=364; citation_issue=15; citation_publication_date=2011; citation_pages=1387-1390; citation_doi=10.1056/NEJMp1102155; citation_id=CR13
citation_journal_title=N Engl J Med; citation_title=Anesthetic neurotoxicity—clinical implications of animal models; citation_author=BA Rappaport, S Suresh, S Hertz, AS Evers, BA Orser; citation_volume=372; citation_issue=9; citation_publication_date=2015; citation_pages=796-797; citation_doi=10.1056/NEJMp1414786; citation_id=CR14
citation_journal_title=J Biol Chem; citation_title=The mitochondrial pathway of anesthetic isoflurane-induced apoptosis; citation_author=Y Zhang, Y Dong, X Wu, Y Lu, Z Xu, A Knapp, Y Yue, T Xu, Z Xie; citation_volume=285; citation_issue=6; citation_publication_date=2010; citation_pages=4025-4037; citation_doi=10.1074/jbc.M109.065664; citation_id=CR15
citation_journal_title=Ann Neurol; citation_title=Anesthetics isoflurane and desflurane differently affect mitochondrial function, learning, and memory; citation_author=Y Zhang, Z Xie; citation_volume=72; citation_issue=4; citation_publication_date=2012; citation_pages=630; citation_doi=10.1002/ana.23683; citation_id=CR16
citation_journal_title=Neurobiol Dis; citation_title=The abolishment of anesthesia-induced cognitive impairment by timely protection of mitochondria in the developing rat brain: the importance of free oxygen radicals and mitochondrial integrity; citation_author=A Boscolo, JA Starr, V Sanchez, N Lunardi, MR DiGruccio, C Ori, A Erisir, P Trimmer, J Bennett, V Jevtovic-Todorovic; citation_volume=45; citation_issue=3; citation_publication_date=2012; citation_pages=1031-1041; citation_doi=10.1016/j.nbd.2011.12.022; citation_id=CR17
citation_journal_title=Anesthesiology; citation_title=Early exposure to general anesthesia disturbs mitochondrial fission and fusion in the developing rat brain; citation_author=A Boscolo, D Milanovic, JA Starr, V Sanchez, A Oklopcic, L Moy, CC Ori, A Erisir, V Jevtovic-Todorovic; citation_volume=118; citation_issue=5; citation_publication_date=2013; citation_pages=1086-1097; citation_doi=10.1097/ALN.0b013e318289bc9b; citation_id=CR18
citation_journal_title=Mol Neurobiol; citation_title=Vitamin C attenuates isoflurane-induced caspase-3 activation and cognitive impairment; citation_author=B Cheng, Y Zhang, A Wang, Y Dong, Z Xie; citation_publication_date=2014; citation_id=CR19
citation_journal_title=Am J Physiol Heart Circ Physiol; citation_title=Isoflurane activates rat mitochondrial ATP-sensitive K+ channels reconstituted in lipid bilayers; citation_author=Y Nakae, WM Kwok, ZJ Bosnjak, MT Jiang; citation_volume=284; citation_issue=5; citation_publication_date=2003; citation_pages=H1865-1871; citation_doi=10.1152/ajpheart.01031.2002; citation_id=CR20
citation_journal_title=Anesth Analg; citation_title=Isoflurane activates human cardiac mitochondrial adenosine triphosphate-sensitive K+ channels reconstituted in lipid bilayers; citation_author=MT Jiang, Y Nakae, M Ljubkovic, WM Kwok, DF Stowe, ZJ Bosnjak; citation_volume=105; citation_issue=4; citation_publication_date=2007; citation_pages=926-932; citation_doi=10.1213/01.ane.0000278640.81206.92; citation_id=CR21
citation_journal_title=Anesth Analg; citation_title=Intracellular mechanism of mitochondrial adenosine triphosphate-sensitive potassium channel activation with isoflurane; citation_author=Y Nakae, S Kohro, QH Hogan, ZJ Bosnjak; citation_volume=97; citation_issue=4; citation_publication_date=2003; citation_pages=1025-1032; citation_doi=10.1213/01.ANE.0000077072.67502.CC; citation_id=CR22
citation_journal_title=Basic Res Cardiol; citation_title=Opening of ATP-sensitive potassium channels causes generation of free radicals in vascular smooth muscle cells; citation_author=M Krenz, O Oldenburg, H Wimpee, MV Cohen, KD Garlid, SD Critz, JM Downey, JN Benoit; citation_volume=97; citation_issue=5; citation_publication_date=2002; citation_pages=365-373; citation_doi=10.1007/s003950200045; citation_id=CR23
citation_journal_title=Am J Physiol Heart Circ Physiol; citation_title=Opening mitoKATP increases superoxide generation from complex I of the electron transport chain; citation_author=A Andrukhiv, AD Costa, IC West, KD Garlid; citation_volume=291; citation_issue=5; citation_publication_date=2006; citation_pages=H2067-2074; citation_doi=10.1152/ajpheart.00272.2006; citation_id=CR24
citation_journal_title=AJP: Heart and Circulatory Physiology; citation_title=Mechanism of reactive oxygen species generation after opening of mitochondrial KATP channels; citation_author=RC Kukreja; citation_volume=291; citation_issue=5; citation_publication_date=2006; citation_pages=H2041-H2043; citation_id=CR25
citation_journal_title=Basic Res Cardiol; citation_title=<Opening mitochondrial KATP in the heart—what happens, and what does not happen.pdf>; citation_author=KD Garlid; citation_volume=95; citation_publication_date=2000; citation_pages=275-279; citation_doi=10.1007/s003950070046; citation_id=CR26
citation_journal_title=J Biol Chem; citation_title=Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes; citation_author=TL Vanden Hoek, LB Becker, Z Shao, C Li, PT Schumacker; citation_volume=273; citation_issue=29; citation_publication_date=1998; citation_pages=18092-18098; citation_doi=10.1074/jbc.273.29.18092; citation_id=CR27
citation_journal_title=J Biol Chem; citation_title=Identification and properties of a novel intracellular (mitochondrial) ATP-sensitive potassium channel in brain; citation_author=R Bajgar, S Seetharaman, AJ Kowaltowski, KD Garlid, P Paucek; citation_volume=276; citation_issue=36; citation_publication_date=2001; citation_pages=33369-33374; citation_doi=10.1074/jbc.M103320200; citation_id=CR28
citation_journal_title=Anesthesiology; citation_title=Mechanisms of isoflurane-induced myocardial preconditioning in rabbits; citation_author=MS Ismaeil, I Tkachenko, AK Gamperl, RF Hickey, BA Cason; citation_volume=90; citation_issue=3; citation_publication_date=1999; citation_pages=812-821; citation_doi=10.1097/00000542-199903000-00024; citation_id=CR29
citation_journal_title=Anesth Analg; citation_title=Inhibition of mitochondrial permeability transition enhances isoflurane-induced cardioprotection during early reperfusion: the role of mitochondrial KATP channels; citation_author=JG Krolikowski, M Bienengraeber, D Weihrauch, DC Warltier, JR Kersten, PS Pagel; citation_volume=101; citation_issue=6; citation_publication_date=2005; citation_pages=1590-1596; citation_doi=10.1213/01.ANE.0000181288.13549.28; citation_id=CR30
citation_journal_title=J Neurosci; citation_title=The inhalation anesthetic isoflurane induces a vicious cycle of apoptosis and amyloid beta-protein accumulation; citation_author=Z Xie, Y Dong, U Maeda, RD Moir, W Xia, DJ Culley, G Crosby, RE Tanzi; citation_volume=27; citation_issue=6; citation_publication_date=2007; citation_pages=1247-1254; citation_doi=10.1523/JNEUROSCI.5320-06.2007; citation_id=CR31
citation_journal_title=J Cereb Blood Flow Metab; citation_title=Isoflurane anesthesia induced persistent, progressive memory impairment, caused a loss of neural stem cells, and reduced neurogenesis in young, but not adult, rodents; citation_author=C Zhu, J Gao, N Karlsson, Q Li, Y Zhang, Z Huang, H Li, HG Kuhn, K Blomgren; citation_volume=30; citation_issue=5; citation_publication_date=2010; citation_pages=1017-1030; citation_doi=10.1038/jcbfm.2009.274; citation_id=CR32
citation_journal_title=J Neurosci; citation_title=Isoflurane-induced caspase-3 activation is dependent on cytosolic calcium and can be attenuated by memantine; citation_author=G Zhang, Y Dong, B Zhang, F Ichinose, X Wu, DJ Culley, G Crosby, RE Tanzi, Z Xie; citation_volume=28; citation_issue=17; citation_publication_date=2008; citation_pages=4551-4560; citation_doi=10.1523/JNEUROSCI.5694-07.2008; citation_id=CR33
citation_journal_title=Biochem Biophys Res Commun; citation_title=A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1); citation_author=A Cossarizza, M Baccarani-Contri, G Kalashnikova, C Franceschi; citation_volume=197; citation_issue=1; citation_publication_date=1993; citation_pages=40-45; citation_doi=10.1006/bbrc.1993.2438; citation_id=CR34
Lipp H-P LO, GalsworthyM, Vyssotski AL, Vyssotski DL, Zinn P, et al. (2006) Automated behavioral analysis of mice using INTELLICAGE: inter-laboratory comparisons and validation with exploratory behavior and spatial learning. Proceedings of Measuring Behavior 2005 Fifth international conference on methods and techniques in behavioral research:66-69
citation_journal_title=Curr Alzheimer Res; citation_title=The potential dual effects of anesthetic isoflurane on Abeta-induced apoptosis; citation_author=Z Xu, Y Dong, X Wu, J Zhang, S McAuliffe, C Pan, Y Zhang, F Ichinose, Y Yue, Z Xie; citation_volume=8; citation_issue=7; citation_publication_date=2011; citation_pages=741-752; citation_doi=10.2174/156720511797633223; citation_id=CR36
citation_journal_title=Exp Neurobiol; citation_title=The role of oxidative stress in neurodegenerative diseases; citation_author=GH Kim, JE Kim, SJ Rhie, S Yoon; citation_volume=24; citation_issue=4; citation_publication_date=2015; citation_pages=325-340; citation_doi=10.5607/en.2015.24.4.325; citation_id=CR37
citation_journal_title=Anesth Analg; citation_title=Preconditioning by isoflurane is mediated by reactive oxygen species generated from mitochondrial electron transport chain complex III; citation_author=LM Ludwig, K Tanaka, JT Eells, D Weihrauch, PS Pagel, JR Kersten, DC Warltier; citation_volume=99; citation_issue=5; citation_publication_date=2004; citation_pages=1308-1315; citation_doi=10.1213/01.ANE.0000134804.09484.5D; citation_id=CR38
citation_journal_title=Anesthesiology; citation_title=Isoflurane differentially modulates mitochondrial reactive oxygen species production via forward versus reverse electron transport flow: implications for preconditioning; citation_author=N Hirata, YH Shim, D Pravdic, NL Lohr, PF Pratt, D Weihrauch, JR Kersten, DC Warltier, ZJ Bosnjak, M Bienengraeber; citation_volume=115; citation_issue=3; citation_publication_date=2011; citation_pages=531-540; citation_doi=10.1097/ALN.0b013e31822a2316; citation_id=CR39
citation_journal_title=Anesth Analg; citation_title=Isoflurane selectively inhibits distal mitochondrial complex I in Caenorhabditis elegans; citation_author=EB Kayser, W Suthammarak, PG Morgan, MM Sedensky; citation_volume=112; citation_issue=6; citation_publication_date=2011; citation_pages=1321-1329; citation_doi=10.1213/ANE.0b013e3182121d37; citation_id=CR40
citation_journal_title=J Physiol; citation_title=Mitochondrial formation of reactive oxygen species; citation_author=JF Turrens; citation_volume=552; citation_issue=Pt 2; citation_publication_date=2003; citation_pages=335-344; citation_doi=10.1113/jphysiol.2003.049478; citation_id=CR41
citation_journal_title=Am J Physiol Heart Circ Physiol; citation_title=The direct physiological effects of mitoK(ATP) opening on heart mitochondria; citation_author=AD Costa, CL Quinlan, A Andrukhiv, IC West, M Jaburek, KD Garlid; citation_volume=290; citation_issue=1; citation_publication_date=2006; citation_pages=H406-415; citation_doi=10.1152/ajpheart.00794.2005; citation_id=CR42
citation_journal_title=J Biol Chem; citation_title=Superoxide radical formation by pure complex I (NADH:ubiquinone oxidoreductase) from Yarrowia lipolytica; citation_author=A Galkin, U Brandt; citation_volume=280; citation_issue=34; citation_publication_date=2005; citation_pages=30129-30135; citation_doi=10.1074/jbc.M504709200; citation_id=CR43
citation_journal_title=Circ Res; citation_title=Opening of mitochondrial K(ATP) channels triggers the preconditioned state by generating free radicals; citation_author=T Pain, XM Yang, SD Critz, Y Yue, A Nakano, GS Liu, G Heusch, MV Cohen, JM Downey; citation_volume=87; citation_issue=6; citation_publication_date=2000; citation_pages=460-466; citation_doi=10.1161/01.RES.87.6.460; citation_id=CR44
citation_journal_title=Anesthesiology; citation_title=Anesthetic effects on mitochondrial ATP-sensitive K channel; citation_author=S Kohro, QH Hogan, Y Nakae, M Yamakage, ZJ Bosnjak; citation_volume=95; citation_issue=6; citation_publication_date=2001; citation_pages=1435-1340; citation_doi=10.1097/00000542-200112000-00024; citation_id=CR45
citation_journal_title=Behav Brain Res; citation_title=Conditioned response suppression in the IntelliCage: assessment of mouse strain differences and effects of hippocampal and striatal lesions on acquisition and retention of memory; citation_author=V Voikar, G Colacicco, O Gruber, E Vannoni, HP Lipp, DP Wolfer; citation_volume=213; citation_issue=2; citation_publication_date=2010; citation_pages=304-312; citation_doi=10.1016/j.bbr.2010.05.019; citation_id=CR46
citation_journal_title=J Neurosci; citation_title=MicroRNA loss enhances learning and memory in mice; citation_author=W Konopka, A Kiryk, M Novak, M Herwerth, JR Parkitna, M Wawrzyniak, A Kowarsch, P Michaluk, J Dzwonek, T Arnsperger, G Wilczynski, M Merkenschlager, FJ Theis, G Kohr, L Kaczmarek, G Schutz; citation_volume=30; citation_issue=44; citation_publication_date=2010; citation_pages=14835-14842; citation_doi=10.1523/JNEUROSCI.3030-10.2010; citation_id=CR47
citation_journal_title=Behav Brain Res; citation_title=Impaired behavior of female tg-ArcSwe APP mice in the IntelliCage: a longitudinal study; citation_author=A Codita, A Gumucio, L Lannfelt, P Gellerfors, B Winblad, AH Mohammed, LN Nilsson; citation_volume=215; citation_issue=1; citation_publication_date=2010; citation_pages=83-94; citation_doi=10.1016/j.bbr.2010.06.034; citation_id=CR48
citation_journal_title=Behav Brain Res; citation_title=Detection of early behavioral markers of Huntington’s disease in R6/2 mice employing an automated social home cage; citation_author=O Rudenko, V Tkach, V Berezin, E Bock; citation_volume=203; citation_issue=2; citation_publication_date=2009; citation_pages=188-199; citation_doi=10.1016/j.bbr.2009.04.034; citation_id=CR49
citation_journal_title=Proc Natl Acad Sci U S A; citation_title=A robust automated system elucidates mouse home cage behavioral structure; citation_author=EH Goulding, AK Schenk, P Juneja, AW MacKay, JM Wade, LH Tecott; citation_volume=105; citation_issue=52; citation_publication_date=2008; citation_pages=20575-20582; citation_doi=10.1073/pnas.0809053106; citation_id=CR50
citation_journal_title=Anesth Analg; citation_title=Glucose may attenuate isoflurane-induced caspase-3 activation in H4 human neuroglioma cells; citation_author=Y Sun, Y Zhang, B Cheng, Y Dong, C Pan, T Li, Z Xie; citation_volume=119; citation_issue=6; citation_publication_date=2014; citation_pages=1373-1380; citation_doi=10.1213/ANE.0000000000000383; citation_id=CR51
citation_journal_title=Anesth Analg; citation_title=2-Deoxy-D-glucose attenuates isoflurane-induced cytotoxicity in an in vitro cell culture model of H4 human neuroglioma cells; citation_author=J Zhang, Y Dong, Z Xu, Y Zhang, C Pan, S McAuliffe, F Ichinose, Y Yue, W Liang, Z Xie; citation_volume=113; citation_issue=6; citation_publication_date=2011; citation_pages=1468-1475; citation_doi=10.1213/ANE.0b013e31822e913c; citation_id=CR52
citation_journal_title=Med Gas Res; citation_title=Propofol and magnesium attenuate isoflurane-induced caspase-3 activation via inhibiting mitochondrial permeability transition pore; citation_author=Y Zhang, Y Dong, Z Xu, Z Xie; citation_volume=2; citation_issue=1; citation_publication_date=2012; citation_pages=20; citation_doi=10.1186/2045-9912-2-20; citation_id=CR53
citation_journal_title=J Physiol; citation_title=K(ATP) channel-independent targets of diazoxide and 5-hydroxydecanoate in the heart; citation_author=PJ Hanley, M Mickel, M Loffler, U Brandt, J Daut; citation_volume=542; citation_issue=Pt 3; citation_publication_date=2002; citation_pages=735-741; citation_doi=10.1113/jphysiol.2002.023960; citation_id=CR54