Skip to main content
SpringerLink
Log in

Modulation of 1-methyl-4-phenylpyridinium-induced mitochondrial dysfunction and cell death in PC12 cells by KATP channel block

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary.

The present study investigated the effect of 5-hydroxydecanoate, a selective mitochondrial KATP channel blocker, on the cytotoxicity of neurotoxin 1-methyl-4-phenylpyridinium (MPP+) in differentiated PC12 cells. 5-Hydroxydecanoate and glibenclamide (a cell surface and mitochondrial KATP channel inhibitor) reduced the MPP+-induced cell death and GSH depletion and showed a maximal inhibitory effect at 5 and 10 µM, respectively. Addition of 5-hydroxydecanoate attenuated the MPP+-induced nuclear damage, changes in the mitochondrial membrane permeability and increase in the reactive oxygen species formation in PC12 cells. The results show that 5-hydroxydecanote may prevent the MPP+-induced viability loss in PC12 cells by suppressing formation of the mitochondrial permeability transition, leading to the cytochrome c release and caspase-3 activation. This effect appears to be accomplished by the inhibitory action on the formation of reactive oxygen species and the depletion of GSH. The blockade of mitochondrial KATP channels seems to prevent the MPP+-induced neuronal cell damage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • MV Avshalumov ME Rice (2003) ArticleTitleActivation of ATP-sensitive K+ (KATP) channels by H2O2 underlies glutamate-dependent inhibition of striatal dopamine release Proc Natl Acad Sci USA 100 11729–11734 Occurrence Handle13679582 Occurrence Handle10.1073/pnas.1834314100 Occurrence Handle1:CAS:528:DC%2BD3sXotFKmtbk%3D

    Article  PubMed  CAS  Google Scholar 

  • E Belisle AJ Kowaltowski (2002) ArticleTitleOpening of mitochondrial K+ channels increases ischemic ATP levels by preventing hydrolysis J Bioenerg Biomembr 34 285–298 Occurrence Handle12392192 Occurrence Handle10.1023/A:1020256502583 Occurrence Handle1:CAS:528:DC%2BD38XntFGrt7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • GC Brown (1999) ArticleTitleNitric oxide and mitochondrial respiration Biochim Biophys Acta 1411 351–369 Occurrence Handle10320668 Occurrence Handle10.1016/S0005-2728(99)00025-0 Occurrence Handle1:CAS:528:DyaK1MXjsF2qtrY%3D

    Article  PubMed  CAS  Google Scholar 

  • DW Busija Z Lacza N Rajapakse K Shimizu B Kis F Bari F Domoki T Horiguchi (2004) ArticleTitleTargeting mitochondrial ATP-sensitive potassium channels-a novel approach to neuroprotection Brain Res Rev 46 282–294 Occurrence Handle15571770 Occurrence Handle10.1016/j.brainresrev.2004.06.011 Occurrence Handle1:CAS:528:DC%2BD2cXhtVantL3F

    Article  PubMed  CAS  Google Scholar 

  • DS Cassarino JK Parks WD Parker SuffixJr JP Bennett SuffixJr (1999) ArticleTitleThe Parkinsonian neurotoxin MPP+ opens the mitochondrial permeability transition pore and releases cytochrome c in isolated mitochondria via an oxidative mechanism Biochim Biophys Acta 1453 49–62 Occurrence Handle9989245 Occurrence Handle1:CAS:528:DyaK1MXosFagtw%3D%3D

    PubMed  CAS  Google Scholar 

  • J Chandra A Samali S Orrenius (2000) ArticleTitleTriggering and modulation of apoptosis by oxidative stress Free Radic Biol Med 29 323–333 Occurrence Handle11035261 Occurrence Handle10.1016/S0891-5849(00)00302-6 Occurrence Handle1:CAS:528:DC%2BD3cXnslWmt7s%3D

    Article  PubMed  CAS  Google Scholar 

  • PC Constantini BC Chernyak V Petronilli P Bernardi (1996) ArticleTitleModulation of the mitochondrial permeability transition pore by pyridine nucleotides and dithiol oxidation at two separate sites J Biol Chem 271 6746–6751 Occurrence Handle10.1074/jbc.271.12.6746

    Article  Google Scholar 

  • MT Crow K Mani Y-J Nam RN Kitsis (2004) ArticleTitleThe mitochondrial death pathway and cardiac myocyte apoptosis Circ Res 95 957–970 Occurrence Handle15539639 Occurrence Handle10.1161/01.RES.0000148632.35500.d9 Occurrence Handle1:CAS:528:DC%2BD2cXpt1GhsLc%3D

    Article  PubMed  CAS  Google Scholar 

  • G Debska R May A Kicińska A Szewczyk CE Elger WS Kunz (2001) ArticleTitlePotassium channel openers depolarize hippocampal mitochondria Brain Res 892 42–50 Occurrence Handle11172747 Occurrence Handle10.1016/S0006-8993(00)03187-5 Occurrence Handle1:CAS:528:DC%2BD3MXhtFSlsrk%3D

    Article  PubMed  CAS  Google Scholar 

  • P dos Santos AJ Kowaltowski MN Laclau S Seetharaman P Paucek S Boudina JB Thambo L Tariosse KD Garlid (2002) ArticleTitleMechanisms by which opening the mitochondrial ATP-sensitive K+ channel protects the ischemic heart Am J Physiol Heart Circ Physiol 283 H284–H295 Occurrence Handle12063301 Occurrence Handle1:CAS:528:DC%2BD38XlsVCks78%3D

    PubMed  CAS  Google Scholar 

  • HTF Facundo JG de Paula AJ Kowaltowski (2005) ArticleTitleMitochondrial ATP-sensitive K+ channels prevent oxidative stress, permeability transition and cell death J Bioenerg Biomembr 37 75–82 Occurrence Handle15906152 Occurrence Handle10.1007/s10863-005-4130-1 Occurrence Handle1:CAS:528:DC%2BD2MXktlKkt7o%3D

    Article  PubMed  CAS  Google Scholar 

  • C Fleury B Mignotte J-L Vayssiere (2002) ArticleTitleMitochondrial reactive oxygen species in cell death signaling Biochimie 84 131–141 Occurrence Handle12022944 Occurrence Handle10.1016/S0300-9084(02)01369-X Occurrence Handle1:CAS:528:DC%2BD38XktVCqsr0%3D

    Article  PubMed  CAS  Google Scholar 

  • W Fu H Luo S Parthasarathy MP Mattson (1998) ArticleTitleCatecholamines potentiate amyloid β-peptide neurotoxicity: involvement of oxidative stress, mitochondrial dysfunction, and perturbed calcium homeostasis Neurobiol Dis 5 229–243 Occurrence Handle9848093 Occurrence Handle10.1006/nbdi.1998.0192 Occurrence Handle1:CAS:528:DyaK1cXnsFGntbY%3D

    Article  PubMed  CAS  Google Scholar 

  • Y Goodman MP Mattson (1996) ArticleTitleK+ channel openers protect hippocampal neurons against oxidative injury and amyloid β-peptide toxicity Brain Res 706 328–332 Occurrence Handle8822377 Occurrence Handle10.1016/0006-8993(95)01367-9 Occurrence Handle1:CAS:528:DyaK28Xns1ygtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • AG Hall (1999) ArticleTitleThe role of glutathione in the regulation of apoptosis Eur J Clin Invest 29 238–245 Occurrence Handle10202381 Occurrence Handle10.1046/j.1365-2362.1999.00447.x Occurrence Handle1:CAS:528:DyaK1MXhvFKit70%3D

    Article  PubMed  CAS  Google Scholar 

  • RE Heikkila A Hess RC Duvoisin (1984) ArticleTitleDopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice Science 224 467–469 Occurrence Handle10.1126/science.6610213

    Article  Google Scholar 

  • EL Holmuhamedov S Jovanović P Dzeja A Jovanović A Terzic (1998) ArticleTitleMitochondrial ATP-sensitive K+ channels modulate cardiac mitochondrial function Am J Physiol 275 H1567–H1576 Occurrence Handle9815062 Occurrence Handle1:CAS:528:DyaK1cXnsF2hsbo%3D

    PubMed  CAS  Google Scholar 

  • JS Isenberg JE Klaunig (2000) ArticleTitleRole of the mitochondrial membrane permeability transition (MPT) in rotenone-induced apoptosis in liver cells Toxicol Sci 53 340–351 Occurrence Handle10696782 Occurrence Handle10.1093/toxsci/53.2.340 Occurrence Handle1:CAS:528:DC%2BD3cXhtF2ksL4%3D

    Article  PubMed  CAS  Google Scholar 

  • P Jenner (2003) ArticleTitleOxidative stress in Parkinson’s disease Ann Neurol 53 IssueIDSuppl 3 S26–S38 Occurrence Handle12666096 Occurrence Handle10.1002/ana.10483 Occurrence Handle1:CAS:528:DC%2BD3sXjtFGitLs%3D

    Article  PubMed  CAS  Google Scholar 

  • R Kim M Emi K Tanabe (2006) ArticleTitleRole of mitochondria as the gardens of cell death Cancer Chemother Pharmacol 57 545–553 Occurrence Handle16175394 Occurrence Handle10.1007/s00280-005-0111-7 Occurrence Handle1:CAS:528:DC%2BD28XhsVartb8%3D

    Article  PubMed  CAS  Google Scholar 

  • K Kimoto K Suzuki T Kizaki Y Hitomi H Ishida H Katsuta E Itoh T Ookawara K Suzuki K Honke H Ohno (2003) ArticleTitleGliclazide protects pancreatic β-cells from damage by hydrogen peroxide Biochem Biophys Res Commun 303 112–119 Occurrence Handle12646174 Occurrence Handle10.1016/S0006-291X(03)00310-3 Occurrence Handle1:CAS:528:DC%2BD3sXitFahurw%3D

    Article  PubMed  CAS  Google Scholar 

  • CS Lee JH Han YY Jang JH Song ES Han (2002) ArticleTitleDifferential effect of catecholamines and MPP+ on membrane permeability in brain mitochondria and cell viability in PC12 cells Neurochem Int 40 361–369 Occurrence Handle11792467 Occurrence Handle10.1016/S0197-0186(01)00069-9 Occurrence Handle1:CAS:528:DC%2BD38XktVOjtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • CS Lee SY Park HH Ko JH Song YK Shin ES Han (2005) ArticleTitleInhibition of MPP+-induced mitochondrial damage and cell death by trifluoperazine and W-7 in PC12 cells Neurochem Int 46 169–178 Occurrence Handle15627517 Occurrence Handle10.1016/j.neuint.2004.07.007 Occurrence Handle1:CAS:528:DC%2BD2cXhtFGhtbjF

    Article  PubMed  CAS  Google Scholar 

  • HW Liang Q Xia IC Bruce (2005) ArticleTitleReactive oxygen species mediate the neuroprotection conferred by a mitochondrial ATP-sensitive potassium channel opener during ischemia in the rat hippocampal slice Brain Res 1042 169–175 Occurrence Handle15854588 Occurrence Handle10.1016/j.brainres.2005.02.031 Occurrence Handle1:CAS:528:DC%2BD2MXjs1Cqu7s%3D

    Article  PubMed  CAS  Google Scholar 

  • D Liu JR Slevin C Lu SL Chan M Hansson E Elmér MP Mattson (2003) ArticleTitleInvolvement of mitochondrial K+ release and cellular efflux in ischemic and apoptotic neuronal death J Neurochem 86 966–979 Occurrence Handle12887694 Occurrence Handle10.1046/j.1471-4159.2003.01913.x Occurrence Handle1:CAS:528:DC%2BD3sXmslOgsb4%3D

    Article  PubMed  CAS  Google Scholar 

  • J Lotharius LL Dugan KL O’Malley (1999) ArticleTitleDistinct mechanisms underlie neurotoxin-mediated cell death in cultured dopaminergic neurons J Neurosci 19 1284–1293 Occurrence Handle9952406 Occurrence Handle1:CAS:528:DyaK1MXhtFOhsrw%3D

    PubMed  CAS  Google Scholar 

  • T Mosmann (1983) ArticleTitleRapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays J Immunol Methods 65 55–63 Occurrence Handle6606682 Occurrence Handle10.1016/0022-1759(83)90303-4 Occurrence Handle1:STN:280:BiuD1cbgsFE%3D

    Article  PubMed  CAS  Google Scholar 

  • K Nagy B Kis NC Rajapakse F Bari DW Busija (2004) ArticleTitleDiazoxide preconditioning protects against neuronal cell death by attenuation of oxidative stress upon glutamate stimulation J Neurosci Res 76 697–704 Occurrence Handle15139028 Occurrence Handle10.1002/jnr.20120 Occurrence Handle1:CAS:528:DC%2BD2cXks12ltLs%3D

    Article  PubMed  CAS  Google Scholar 

  • FA Oberhammer M Pavelka S Sharma R Tiefenbacher AF Purchio W Bursch R Schulte-Hermann (1992) ArticleTitleInduction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor β1 Proc Natl Acad Sci USA 89 5408–5412 Occurrence Handle1608949 Occurrence Handle10.1073/pnas.89.12.5408 Occurrence Handle1:CAS:528:DyaK38XksVGqu7o%3D

    Article  PubMed  CAS  Google Scholar 

  • CW Olanow WG Tatton (1999) ArticleTitleEtiology and pathogenesis of Parkinson’s disease Annu Rev Neurosci 22 123–144 Occurrence Handle10202534 Occurrence Handle10.1146/annurev.neuro.22.1.123 Occurrence Handle1:CAS:528:DyaK1MXhvFemsro%3D

    Article  PubMed  CAS  Google Scholar 

  • S Przedborski V Jackson-Lewis (1998) ArticleTitleMechanism of MPTP toxicity Mov Disord 13 35–38 Occurrence Handle9613716

    PubMed  Google Scholar 

  • S Przedborski V Jackson-Lewis R Djaldetti G Liberatore M Vila S Vukosaic G Almer (2000) ArticleTitleThe parkisonian toxin MPTP: action and mechanism Restor Neurol Neurosci 16 135–142 Occurrence Handle12671216 Occurrence Handle1:CAS:528:DC%2BD3cXis1aksbk%3D

    PubMed  CAS  Google Scholar 

  • N Rajapakse B Kis T Horiguchi J Snipes D Busija (2003) ArticleTitleDiazoxide pretreatment induces delayed preconditioning in astrocytes against oxygen glucose deprivation and hydrogen peroxide-induced toxicity J Neurosci Res 73 206–214 Occurrence Handle12836163 Occurrence Handle10.1002/jnr.10657 Occurrence Handle1:CAS:528:DC%2BD3sXlsFahsrs%3D

    Article  PubMed  CAS  Google Scholar 

  • A Szewczyk E Marbán (1999) ArticleTitleMitochondria: a new target for K+ channel openers? Trends Pharmacol Sci 20 157–161 Occurrence Handle10322501 Occurrence Handle10.1016/S0165-6147(99)01301-2 Occurrence Handle1:CAS:528:DyaK1MXksVyns7Y%3D

    Article  PubMed  CAS  Google Scholar 

  • KK Tai DD Truong (2002) ArticleTitleActivation of adenine triphosphate-sensitive potassium channels confers protection against rotenone-induced cell death: therapeutic implications for Parkinson’s disease J Neurosci Res 69 559–566 Occurrence Handle12210849 Occurrence Handle10.1002/jnr.10309 Occurrence Handle1:CAS:528:DC%2BD38XmtVOgsrk%3D

    Article  PubMed  CAS  Google Scholar 

  • K-W Tai ZA McCrossan GW Abbott (2003) ArticleTitleActivation of mitochondrial ATP-sensitive potassium channels increases cell viability against rotenone-induced cell death J Neurochem 84 1193–1200 Occurrence Handle12603842 Occurrence Handle10.1046/j.1471-4159.2003.01625.x Occurrence Handle1:CAS:528:DC%2BD3sXit1ejtbo%3D

    Article  PubMed  CAS  Google Scholar 

  • WG Tatton RME Chalmers-Redman WJH Ju M Mammen GW Carlile AW Pong NA Tatton (2002) ArticleTitlePropargylamines induce antiapoptotic new protein synthesis in serum-and nerve growth factor (NGF)-withdrawn, NGF-differentiated PC-12 cells J Pharmacol Exp Ther 301 753–764 Occurrence Handle11961082 Occurrence Handle10.1124/jpet.301.2.753 Occurrence Handle1:CAS:528:DC%2BD38XjtlKisL8%3D

    Article  PubMed  CAS  Google Scholar 

  • RJ van Klaveren PHM Hoet JL Pype M Demedts B Nemery (1997) ArticleTitleIncrease in γ-glutamyltransferase by glutathione depletion in rat type II pneumocytes Free Radic Biol Med 22 525–534 Occurrence Handle8981045 Occurrence Handle10.1016/S0891-5849(96)00375-9 Occurrence Handle1:CAS:528:DyaK2sXitFKhtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  • T Yamauchi S Kashii H Yasuyoshi S Zhang Y Honda A Akaike (2003) ArticleTitleMitochondrial ATP-sensitive potassium channel: a novel site for neuroprotection Invest Ophthalmol Vis Sci 44 2750–2756 Occurrence Handle12766083 Occurrence Handle10.1167/iovs.02-0815

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea

    C. S. Lee, Y. J. Kim, H. H. Ko & E. S. Han

Authors
  1. C. S. Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. J. Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. H. Ko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. S. Han
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, C., Kim, Y., Ko, H. et al. Modulation of 1-methyl-4-phenylpyridinium-induced mitochondrial dysfunction and cell death in PC12 cells by KATP channel block. J Neural Transm 114, 297–305 (2007). https://doi.org/10.1007/s00702-006-0594-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-006-0594-3

Search

Navigation