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Chemical preconditioning: A cytoprotective strategy

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Abstract

Brief ischemic or hypoxic episodes may increase or decrease tolerance towards subsequent severe ischemia in heart and brain. A similar phenomenon is observed after mild chemical inhibition of oxidative phosphorylation – chemical preconditioning. We have shown that chemical preconditioning can be induced by chemical inhibition of mitochondrial complex I and mitochondrial complex II. With a time interval of three hours between chemical pretreatment and massive inhibition of oxidative phosphorylation, recovery of population spike amplitude in hippocampal region CA1 after stimulation of the Schaffer collaterals was 31 ± 9% in controls, 98 ± 14% after i.p. treatment with 1 mg/kg body weight haloperidol, an inhibitor of mitochondrial complex I and 90 ± 7% with pretreatment with 3-np, an inhibitor of mitochondrial complex II. Activation of ATP regulated potassium channels partakes in mediating the preconditioning effect. We conclude that chemical preconditioning is a practical prophylactic ph armacologic strategy to increase hypoxic tolerance. (Mol Cell Biochem 174: 249–254, 1997)

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References

  1. Choi DW: Glutamate neurotoxicity and diseases of the nervous system. Neuron 1: 623–634, 1988

    Google Scholar 

  2. Rothman SM, Olney JW: Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann Neurol 19: 105–111, 1986

    Google Scholar 

  3. Albin RL, Greenamyre JT: Alternative excitotoxic hypotheses. Neurology 42: 733–738, 1992

    Google Scholar 

  4. Beal MF: Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? Ann Neurol 31: 119– 130, 1992

    Google Scholar 

  5. Riepe MW, Hori N, Ludolph AC, Carpenter DO: Failure of neuronal ion exchange, not potentiated excitation, causes excitotoxicity after inhibition of oxidative phosphorylation. Neuroscience 64: 91–97, 1995

    Google Scholar 

  6. Kato H, Kogure K, Nakano S: Neuronal damge following repeated brief ischemia in the gerbil. Brain Res 479: 366–370, 1989

    Google Scholar 

  7. Kato H, Liu Y, Araki T, Kogure K: Temporal profile of the effects of pretreatment with brief cerebral ischemia on the neruonal damage following secondary ischemic insult in the gerbil: cumulative damage and protective effects. Brain Res 553: 238–242, 1991

    Google Scholar 

  8. Kitagawa K, Matsumoto M, Tagaya M, Hata R, Ueda H, Niinobe M, Handa N, Fukunaga R, Kimura K, Mikoshiba K, Kamada T: 'Ischemic tolerance' phenomenon found in the brain. Brain Res 528: 21–24, 1990.

    Google Scholar 

  9. Lutz PL: Mechanisms for anoxic survival in the vertebrate brain. Annu Rev Physiol 54: 601–618, 1992

    Google Scholar 

  10. Murry CE, Jennings RB, Reimer KA: Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74: 1124–1136, 1986

    Google Scholar 

  11. Schurr A, Reid KH, Tseng MT, West C, Rigor BM: Adaptation of adult brain tissue to anoxia and hypoxia in vitro. Brain Res 374: 244– 248, 1986

    Google Scholar 

  12. Tomida S, Nowak TSJ, Vass K, Lohr JM, Klatzo I: Experimental model for repetitive ischemic attacks in the gerbil: the cumulative effect of repeated ischemic insults. J. Cerebr. Blood Flow Metab 7: 773– 782, 1987

    Google Scholar 

  13. Tomai F, Crea F, Gaspardone A, Versaci F, De Paulis R, Penta de Peppo a, Chiariello L, Gioffre PA: Ischemic preconditioning during coronary angioplasty is prevented by glibenclamide, a selective ATPsensitive K+ channel blocker. Circulation 90: 700–705, 1994

    Google Scholar 

  14. Auchampach JA, Gross GJ: Adenosine A1 receptors, KATP channels, and ischemic preconditioning in dogs. Am J Physiol 264: H1327–H1336, 1993

    Google Scholar 

  15. Heurteaux C, Lauritzen I, Widmann C, Lazdunski M: Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral ischemic preconditioning. Proc Natl Acad Sci USA 92: 4666–4670, 1995

    Google Scholar 

  16. Van Winkle DM, Chien GL, Wolff RA, Soifer BE, Kuzume K, Davis RF: Cardioprotection provided by adenosine receptor activation is abolished by blockade of the KATP channel. Am J Physiol 266: H829– H839, 1994

    Google Scholar 

  17. Riepe M, Niemi WN, Megow D, Ludolph AC, Carpenter DO: Mitochondrial oxidation in rat hippocampus can be preconditioned by selective chemical inhibition of succinic dehydrogenase. Exp Neurol 138: 15–21, 1996

    Google Scholar 

  18. Coles CJ, Edmondson DE, Singer TP: Inactivation of succinate dehydrogenase by 3-nitropropionate. J Biol Chem 254: 5161–5167, 1979

    Google Scholar 

  19. Ludolph AC, Seelig M, Ludolph A, Novitt P, Allen CN, Spencer PS, Sabri MI: 3-nitropropionic acid decreases cellular energy levels and causes neuronal degeneration in cortical explants. Neurodegeneration 1: 155–161, 1992

    Google Scholar 

  20. Brouillet E, Jenkins BG, Hyman BT, Ferrante RJ, Kowall NW, Srivastava R, Roy DS, Rosen BR, Beal MF: Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid. J Neurochem 60: 356–359, 1993

    Google Scholar 

  21. Burkhardt C, Kelly JP, Lim YH, Filley CM, Parker WDJ: Neuroleptic medications inhibit complex I of the electron transport chain. Ann Neurol 33: 512–517, 1993

    Google Scholar 

  22. Riepe M, Hori N, Ludolph AC, Carpenter DO, Spencer PS, Allen CN: Inhibition of energy metabolism by 3-nitropropionic acid activates ATP-sensitive potassium channels. Brain Res 586: 61–66, 1992

    Google Scholar 

  23. Fujiwara N, Higashi H, Shimoji K, Yoshimura M: Effects of hypoxia on hippocampal neurons in vitro. J Physiol 384: 131–151, 1987

    Google Scholar 

  24. Hansen AJ: Effects of anoxia on distribution in the brain. Physiol Rev 65: 101–148, 1985

    Google Scholar 

  25. Leblond J, Krnjevic K: Hypoxic changes in hippocampal neurons. J Neurophysiol 62: 1–14, 1989

    Google Scholar 

  26. Novelli A, Reilly JA, Lysko PG, Henneberry RC: Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced. Brain Res 451: 205–212, 1988

    Google Scholar 

  27. Simpson JR, Isacson O: Mitochondrial impairment reduces the threshold for in vivo NMDA-mediated neuronal death in the striatum. Exp Neurol 121: 57–64, 1993

    Google Scholar 

  28. Henneberry RC, Novelli A, Cox JA, Lysko PG: Neurotoxicity at the N-methyl-D-aspartate receptor in energy-compromised neurons. An hypothesis for cell death in aging and disease. Ann NY Acad Sci 568: 225–233, 1989

    Google Scholar 

  29. Mayer ML, Westbrook GL, Guthrie PB: Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature 309: 261– 263, 1984

    Google Scholar 

  30. Mody I, Salter MW, MacDonald JF: Requirement of the NMDA receptor/channel for intracellular high-energy phosphates and the extent of intraneuronal calcium buffering in cultured mouse hippocampal neruons. Neurosci Lett 93: 73–78, 1988

    Google Scholar 

  31. Li Y, Kloner RAJ: Cardioprotective effects of ischemic preconditioning can be recaptured after they are lost. J Am Coll Cardiol 23: 470–474, 1994

    Google Scholar 

  32. Liu Y, Kato H, Nakata N, Kogure K: Temporal profile of heat shock protein 70 synthesis in ischemic tolerance induced by preconditioning ischemia in rat hippocampus. Neuroscience 56: 921– 927, 1993

    Google Scholar 

  33. Kitagawa, K, Matsumoto, M, Mandai, K, Mabuchi, T, Matsushita, K, Yanagihara, T and Kamada, T: Ischemic tolerance can be induced in unilateral hippocampus and augmentation of tolerance is not accompanied by increased production of hsp72, Soc Neurosci Abstr Vol 21: 213.4, 1995

    Google Scholar 

  34. Riepe MW, Nakase H, Esclaire F, Kasischke K, Schreiber S, Ludolph AC, Dirnagl U, Hugon J, Kempski O: Increased hypoxic and ischemic tolerance by chemical inhibition of oxidative phosphorylation –' chemical preconditioning'. J Cerebr Blood Flow Metab, in press, 1997

  35. Janssen PAJ: Toxicology and metabolism of butyrophenones. Proc Eur Soc Study Drug Toxi 9: 107–112, 1968

    Google Scholar 

  36. Cervos NJ, Diemer NH: Selective vulnerability in brain hypoxia. Crit Rev Neurobiol 6: 149–182, 1991

    Google Scholar 

  37. Halliwell B, Gutteridge JMC: Oxygen radicals and the nervous system. TINS 8: 22–26, 1985

    Google Scholar 

  38. Siesjö BK, Smith ML: The biochemical basis of ischemic brain lesions. Arzneimittelforschung 41: 288–292, 1991

    Google Scholar 

  39. Riepe MW, Kasischke K, Gericke CA, Löwe A, Hellweg R: Increase of hypoxic tolerance in rat hippocampal slices following 3-nitropropionic acid is not mediated by endogenous nerve growth factor. Neurosci Lett 211: 9–12, 1996

    Google Scholar 

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  1. Department of Neurology, Humboldt University, Berlin, Germany

    Matthias W. Riepe & Albert C. Ludolph

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  1. Matthias W. Riepe
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  2. Albert C. Ludolph
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Riepe, M.W., Ludolph, A.C. Chemical preconditioning: A cytoprotective strategy. Mol Cell Biochem 174, 249–254 (1997). https://doi.org/10.1023/A:1006820927262

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