Journal of Bioenergetics and Biomembranes

, Volume 42, Issue 6, pp 491–497 | Cite as

Brain mitochondria from rats treated with sulforaphane are resistant to redox-regulated permeability transition



Oxidative stress promotes Ca2+-dependent opening of the mitochondrial inner membrane permeability transition pore (PTP), causing bioenergetic failure and subsequent cell death in many paradigms, including those related to acute brain injury. One approach to pre-conditioning against oxidative stress is pharmacologic activation of the Nrf2/ARE pathway of antioxidant gene expression by agents such as sulforaphane (SFP). This study tested the hypothesis that administration of SFP to normal rats increases resistance of isolated brain mitochondria to redox-sensitive PTP opening. SFP or DMSO vehicle was administered intraperitoneally to adult male rats at 10 mg/kg 40 h prior to isolation of non-synaptic brain mitochondria. Mitochondria were suspended in medium containing a respiratory substrate and were exposed to an addition of Ca2+ below the threshold for PTP opening. Subsequent addition of tert-butyl hydroperoxide (tBOOH) resulted in a cyclosporin A-inhibitable release of accumulated Ca2+ into the medium, as monitored by an increase in fluorescence of Calcium Green 5N within the medium, and was preceded by a decrease in the autofluorescence of mitochondrial NAD(P)H. SFP treatment significantly reduced the rate of tBOOH-induced Ca2+ release but did not affect NAD(P)H oxidation or inhibit PTP opening induced by the addition of phenylarsine oxide, a direct sulfhydryl oxidizing agent. SFP treatment had no effect on respiration by brain mitochondria and had no effect on PTP opening or respiration when added directly to isolated mitochondria. We conclude that SFP confers resistance of brain mitochondria to redox-regulated PTP opening, which could contribute to neuroprotection observed with SFP.


Nrf2 Calcium Peroxide Pyridine nucleotide Oxidation/reduction 


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  1. Akao M, O’Rourke B, Teshima Y, Seharaseyon J, Marban E (2003) Circ Res 92:186–194CrossRefGoogle Scholar
  2. Andreyev A, Fahy B, Fiskum G (1998) FEBS Lett 439:373–376CrossRefGoogle Scholar
  3. Angeloni C, Leoncini E, Malaguti M, Angelini S, Hrelia P, Hrelia S (2009) J Agric Food Chem 57:5615–5622CrossRefGoogle Scholar
  4. Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, Molkentin JD (2005) Nature 434:658–662CrossRefGoogle Scholar
  5. Catisti R, Vercesi AE (1999) FEBS Lett 464:97–101CrossRefGoogle Scholar
  6. Costantini P, Belzacq AS, Vieira HL, Larochette N, de Pablo MA, Zamzami N, Susin SA, Brenner C, Kroemer G (2000) Oncogene 19:307–314CrossRefGoogle Scholar
  7. Crane MS, Howie AF, Arthur JR, Nicol F, Crosley LK, Beckett GJ (2009) Biochim Biophys Acta 1790:1191–1197Google Scholar
  8. Danilov CA, Chandrasekaran K, Racz J, Soane L, Zielke C, Fiskum G (2009) Glia 57:645–656CrossRefGoogle Scholar
  9. Dinkova-Kostova AT, Talalay P (2008) Mol Nutr Food Res 52(Suppl 1):S128–S138Google Scholar
  10. Duchen MR (1992) Biochem J 283:41–50Google Scholar
  11. Fiskum G, Murphy AN, Beal MF (1999) J Cereb Blood Flow Metab 19:351–369CrossRefGoogle Scholar
  12. Halestrap AP, McStay GP, Clarke SJ (2002) Biochimie 84:153–166CrossRefGoogle Scholar
  13. Jaiswal AK (2004) Free Radic Biol Med 36:1199–1207CrossRefGoogle Scholar
  14. Kensler TW, Curphey TJ, Maxiutenko Y, Roebuck BD (2000) Drug Metabol Drug Interact 17:3–22Google Scholar
  15. Kowaltowski AJ, Vercesi AE, Fiskum G (2000) Cell Death Differ 7:903–910CrossRefGoogle Scholar
  16. Kristian T, Siesjo BK (1998) Stroke 29:705–718Google Scholar
  17. Lemasters JJ, Theruvath TP, Zhong Z, Nieminen AL (2009) Biochim Biophys Acta 1787:1395–1401CrossRefGoogle Scholar
  18. Linard D, Kandlbinder A, Degand H, Morsomme P, Dietz KJ, Knoops B (2009) Arch Biochem Biophys 491:39–45CrossRefGoogle Scholar
  19. Mirandola SR, Melo DR, Saito A, Castilho RF (2010) J Neurosci Res 88:630–639Google Scholar
  20. Mukherjee S, Gangopadhyay H, Das DK (2008) J Agric Food Chem 56:609–617CrossRefGoogle Scholar
  21. Mukherjee S, Lekli I, Ray D, Gangopadhyay H, Raychaudhuri U, Das DK (2010) Br J Nutr 103:815–823CrossRefGoogle Scholar
  22. Myzak MC, Dashwood WM, Orner GA, Ho E, Dashwood RH (2006) FASEB J 20:506–508Google Scholar
  23. Navarro A, Boveris A (2009) Brain mitochondrial dysfunction and oxidative damage in Parkinson’s disease. J Bioenerg Biomembr 41:517–521CrossRefGoogle Scholar
  24. Navet R, Mouithys-Mickalad A, Douette P, Sluse-Goffart CM, Jarmuszkiewicz W, Sluse FE (2006) J Bioenerg Biomembr 38:23–32CrossRefGoogle Scholar
  25. Niizuma K, Endo H, Chan PH (2009) J Neurochem 109(Suppl 1):133–138CrossRefGoogle Scholar
  26. Okonkwo DO, Povlishock JT (1999) J Cereb Blood Flow Metab 19:443–451CrossRefGoogle Scholar
  27. Petronilli V, Sileikyte J, Zulian A, bbeni-Sala F, Jori G, Gobbo S, Tognon G, Nikolov P, Bernardi P, Ricchelli F (2009) Biochim Biophys Acta 1787:897–904CrossRefGoogle Scholar
  28. Petrosillo G, Moro N, Ruggiero FM, Paradies G (2009) Free Radic Biol Med 47:969–974CrossRefGoogle Scholar
  29. Rasola A, Bernardi P (2007) Apoptosis 12:815–833CrossRefGoogle Scholar
  30. Schinzel AC, Takeuchi O, Huang Z, Fisher JK, Zhou Z, Rubens J, Hetz C, Danial NN, Moskowitz MA, Korsmeyer SJ (2005) Proc Natl Acad Sci USA 102:12005–12010CrossRefGoogle Scholar
  31. Siebert A, Desai V, Chandrasekaran K, Fiskum G, Jafri MS (2009) J Neurosci Res 87:1659–1669CrossRefGoogle Scholar
  32. Soane L, Li DW, Fiskum G, Bambrick LL (2010) J Neurosci Res 88:1355–1363Google Scholar
  33. Starkov AA, Chinopoulos C, Fiskum G (2004) Cell Calcium 36:257–264CrossRefGoogle Scholar
  34. Thimmulappa RK, Mai KH, Srisuma S, Kensler TW, Yamamoto M, Biswal S (2002) Cancer Res 62:5196–5203Google Scholar
  35. Vauzour D, Buonfiglio M, Corona G, Chirafisi J, Vafeiadou K, Angeloni C, Hrelia S, Hrelia P, Spencer JP (2010) Mol Nutr Food Res 54:532–542CrossRefGoogle Scholar
  36. Zhang Y, Talalay P, Cho CG, Posner GH (1992) Proc Natl Acad Sci USA 89:2399–2403CrossRefGoogle Scholar
  37. Zhao J, Moore AN, Clifton GL, Dash PK (2005) J Neurosci Res 82:499–506CrossRefGoogle Scholar
  38. Zhao J, Kobori N, Aronowski J, Dash PK (2006) Neurosci Lett 393:108–112CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Anesthesiology and the Center for ShockTrauma, and Anesthesiology ResearchBaltimoreUSA
  2. 2.Department of AnesthesiologyUniversity of Maryland School of MedicineBaltimoreUSA

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