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Cited by 31Cell death mechanisms and regulationProtein Kinase Regulation and GTPase SignalingNeuroprotection in Cerebral Ischemia

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Neuroprotection by c-Jun NH2-terminal kinase inhibitor SP600125 against potassium deprivation–induced apoptosis involves the Akt pathway and inhibition of cell cycle reentry

Yeste-Velasco, M., Folch, J., Casadesús, G., Smith, M.A., Pallàs, M., Camins, A.·2009·Neuroscience
DOI 10.1016/j.neuroscience.2009.01.035
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Abstract

Increasing evidence implicates the c-Jun NH(2)-terminal kinase (JNK) pathway in the regulation of apoptosis in neurodegenerative diseases. In this study, we examined the neuroprotective effect of SP600125, a selective JNK inhibitor, in cerebellar granule cells (CGNs) deprived of serum and potassium (S/K withdrawal). S/K withdrawal-induced apoptosis occurs via activation of multiple pro-apoptotic pathways, including re-entry into the cell cycle, activation of glycogen synthase kinase-3 beta (GSK-3beta), cyclin-dependent kinase 5 (cdk5/p35) breakdown, formation of cdk5/p25 and JNK activation. Here we demonstrate that SP600125 is able to inhibit all these pro-apoptotic pathways via the inhibition of JNK. Further, we found that JNK inhibition maintains the phosphorylation/activation of Akt after S/K withdrawal. For further confirmation of this result, we studied several targets downstream of Akt including GSK-3beta, p-FOXO1, p-CREB and p35. In addition, the specific PI3K/Akt inhibitor LY294002 greatly diminished the antiapoptotic effects of SP600125 upon S/K withdrawal, confirming that Akt is involved in the neuroprotection achieved by SP600125. These results suggest that the maintenance of the PI3-kinase/Akt pathway by inhibition of JNK contributes to the prevention of apoptosis in rat cerebellar granule neurons mediated by S/K withdrawal. Furthermore, we propose that JNK may regulate the cell cycle re-entry by a novel mechanism that involves Akt, GSK-3beta and Rb phosphorylatio…

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  • Inhibition of JNK and ERK elicited partial protection against K5-induced apoptosis in control CGN, as shown by reduced caspase-3 activation.

    “Inhibition of JNK and ERK elicited partial protection against K5-induced apoptosis in control CGN as shown by reduced caspase-3 activation as evaluated by WB (Fig. 5a, b) [35,36].”

    From PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling (2012) · cites this paper as [36]

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Research works printed but not linked: 49

  1. Alvira, 2007, Inhibition of cyclin-dependent kinases is neuroprotective in 1-methyl-4-phenylpyridinium-induced apoptosis in neurons, Neuroscience, 146, 350, 10.1016/j.neuroscience.2007.01.042 · DOI
  2. Becker, 2005, Beyond proliferation–cell cycle control of neuronal survival and differentiation in the developing mammalian brain, Semin Cell Dev Biol, 16, 439, 10.1016/j.semcdb.2005.02.006 · DOI
  3. Becker, 2004, Characterization of the c-Jun N-terminal kinase-BimEL signaling pathway in neuronal apoptosis, J Neurosci, 24, 8762, 10.1523/JNEUROSCI.2953-04.2004 · DOI · Paper page
  4. Bogush, 2007, AKT and CDK5/p35 mediated brain/derived neurotrophic factor induction of DARPP-32 in medium size spiny neurons in vitro, J Biol Chem, 282, 7352, 10.1074/jbc.M606508200 · DOI
  5. Borsello, 2007, JNK signalling: a possible target to prevent neurodegeneration, Curr Pharm Des, 13, 1875, 10.2174/138161207780858384 · DOI
  6. Bowser, 2002, Cell cycle proteins in Alzheimer's disease: plenty of wheels but no cycle, J Alzheimers Dis, 4, 249, 10.3233/JAD-2002-4316 · DOI
  7. Camins, 2008, Apoptotic mechanisms involved in neurodegenerative diseases: experimental and therapeutic approaches, Methods Find Exp Clin Pharmacol, 30, 43, 10.1358/mf.2008.30.1.1090962 · DOI
  8. Crossthwaite, 2004, Inhibiting Src family tyrosine kinase activity blocks glutamate signalling to ERK1/2 and Akt/PKB but not JNK in cultured striatal neurones, J Neurochem, 88, 1127, 10.1046/j.1471-4159.2004.02257.x · DOI
  9. D'Mello, 1993, Induction of apoptosis in cerebellar granule neurons by low potassium: inhibition of death by insulin-like growth factor I and cAMP, Proc Natl Acad Sci U S A, 90, 10989, 10.1073/pnas.90.23.10989 · DOI · Paper page
  10. Enguita, 2005, Glycogen synthase kinase 3 activity mediates neuronal pentraxin 1 expression and cell death induced by potassium deprivation in cerebellar granule cells, Mol Pharmacol, 67, 1237, 10.1124/mol.104.007062 · DOI
  11. García-Alvarez, 2007, Glycogen synthase kinase-3beta binds to E2F1 and regulates its transcriptional activity, Biochim Biophys Acta, 1773, 375, 10.1016/j.bbamcr.2006.09.015 · DOI
  12. Harris, 2001, BH3-only Bcl-2 family members are coordinately regulated by the JNK pathway and require Bax to induce apoptosis in neurons, J Biol Chem, 276, 37754, 10.1074/jbc.M104073200 · DOI
  13. Harris, 2002, Identification of JNK-dependent and -independent components of cerebellar granule neuron apoptosis, J Neurochem, 83, 992, 10.1046/j.1471-4159.2002.01219.x · DOI
  14. Harris, 2002, Inhibition of the c-Jun N-terminal kinase signaling pathway by the mixed lineage kinase inhibitor CEP-1347 (KT7515) preserves metabolism and growth of trophic factor-deprived neurons, J Neurosci, 22, 103, 10.1523/JNEUROSCI.22-01-00103.2002 · DOI
  15. Konishi, 2003, The E2F-Cdc2 cell-cycle pathway specifically mediates activity deprivation-induced apoptosis of postmitotic neurons, J Neurosci, 23, 1649, 10.1523/JNEUROSCI.23-05-01649.2003 · DOI
  16. Kuan, 2005, Targeting the JNK signaling pathway for stroke and Parkinson's diseases therapy, Curr Drug Targets CNS Neurol Disord, 4, 63, 10.2174/1568007053005145 · DOI
  17. Kruman, 2008, DNA damage response and neuroprotection, Front Biosci, 13, 2504, 10.2741/2862 · DOI
  18. Kyrylenko, 1999, Regulation of PTEN expression in neuronal apoptosis, Brain Res Mol Brain Res, 73, 198, 10.1016/S0169-328X(99)00259-4 · DOI
  19. Li, 2003, Cyclin-dependent kinase-5 is involved in neuregulin-dependent activation of phosphatidylinositol 3-kinase and Akt activity mediating neuronal survival, J Biol Chem, 278, 35702, 10.1074/jbc.M302004200 · DOI
  20. Lotharius, 2005, Progressive degeneration of human mesencephalic neuron-derived cells triggered by dopamine-dependent oxidative stress is dependent on the mixed-lineage kinase pathway, J Neurosci, 25, 6329, 10.1523/JNEUROSCI.1746-05.2005 · DOI
  21. Luo, 2003, Akt as a mediator of cell death, Proc Natl Acad Sci U S A, 100, 11712, 10.1073/pnas.1634990100 · DOI
  22. Ma, 2007, dp5/HRK is a c-Jun target gene and required for apoptosis induced by potassium deprivation in cerebellar granule neurons, J Biol Chem, 282, 30901, 10.1074/jbc.M608694200 · DOI
  23. Miller, 1997, Inhibition of phosphatidylinositol 3-kinase activity blocks depolarization- and insulin-like growth factor I-mediated survival of cerebellar granule cells, J Biol Chem, 272, 9847, 10.1074/jbc.272.15.9847 · DOI
  24. Nagy, 2005, The last neuronal division: a unifying hypothesis for the pathogenesis of Alzheimer's disease, J Cell Mol Med, 9, 531, 10.1111/j.1582-4934.2005.tb00485.x · DOI · Paper page
  25. Nicotera, 1999, Neuronal cell death: a demise with different shapes, Trends Pharmacol Sci, 20, 46, 10.1016/S0165-6147(99)01304-8 · DOI
  26. O'Hare, 2000, Induction and modulation of cerebellar granule neuron death by E2F-1, J Biol Chem, 275, 25358, 10.1074/jbc.M001725200 · DOI
  27. Padmanabhan, 1999, Role of cell cycle regulatory proteins in cerebellar granule neuron apoptosis, J Neurosci, 19, 8747, 10.1523/JNEUROSCI.19-20-08747.1999 · DOI
  28. 2007, Mixed lineage kinase inhibitor CEP-1347 fails to delay disability in early Parkinson disease, Neurology, 69, 1480, 10.1212/01.wnl.0000277648.63931.c0 · DOI
  29. Putcha, 2003, JNK-mediated BIM phosphorylation potentiates Bax-dependent apoptosis, Neuron, 38, 899, 10.1016/S0896-6273(03)00355-6 · DOI
  30. Roux, 2002, K252a and CEP1347 are neuroprotective compounds that inhibit mixed-lineage kinase-3 and induce activation of Akt and ERK, J Biol Chem, 277, 49473, 10.1074/jbc.M203428200 · DOI
  31. Shi, 2005, Activity deprivation-dependent induction of the proapoptotic BH3-only protein Bim is independent of JNK/c-Jun activation during apoptosis in cerebellar granule neurons, Neurosci Lett, 375, 7, 10.1016/j.neulet.2004.10.082 · DOI
  32. Shimoke, 1999, Inhibition of phosphatidylinositol 3-kinase activity elevates c-Jun N-terminal kinase activity in apoptosis of cultured cerebellar granule neurons, Brain Res Dev Brain Res, 112, 245, 10.1016/S0165-3806(98)00172-2 · DOI
  33. Silva, 2005, Mixed lineage kinase-c-jun N-terminal kinase signaling pathway: a new therapeutic target in Parkinson's disease, Mov Disord, 20, 653, 10.1002/mds.20390 · DOI
  34. Smith, 2003, Involvement of the transcription factor E2F1/Rb in kainic acid-induced death of murine cerebellar granule cells, Brain Res Mol Brain Res, 116, 70, 10.1016/S0169-328X(03)00253-5 · DOI
  35. Song, 2005, The activation of Akt/PKB signaling pathway and cell survival, J Cell Mol Med, 9, 59, 10.1111/j.1582-4934.2005.tb00337.x · DOI
  36. Thakur, 2007, c-Jun phosphorylation in Alzheimer disease, J Neurosci Res, 85, 1668, 10.1002/jnr.21298 · DOI
  37. Verdaguer, 2005, Inhibition of multiple pathways accounts for the antiapoptotic effects of flavopiridol on potassium withdrawal-induced apoptosis in neurons, J Mol Neurosci, 26, 71, 10.1385/JMN:26:1:071 · DOI
  38. Verdaguer, 2004, Antiapoptotic effects of roscovitine in cerebellar granule cells deprived of serum and potassium: a cell cycle-related mechanism, Neurochem Int, 44, 251, 10.1016/S0197-0186(03)00147-5 · DOI
  39. Waldmeier, 2006, Recent clinical failures in Parkinson's disease with apoptosis inhibitors underline the need for a paradigm shift in drug discovery for neurodegenerative diseases, Biochem Pharmacol, 72, 1197, 10.1016/j.bcp.2006.06.031 · DOI
  40. Wang, 2004, Mixed-lineage kinase inhibitors require the activation of Trk receptors to maintain long-term neuronal trophism and survival, J Pharmacol Exp Ther, 312, 1007, 10.1124/jpet.104.077800 · DOI
  41. Wang, 2004, SP606125 a new JNK inhibitor, protects dopaminergic neurons in the MPTP model of Parkinson's disease, Neurosci Res, 48, 195, 10.1016/j.neures.2003.10.012 · DOI
  42. Webber, 2005, The cell cycle in Alzheimer disease: a unique target for neuropharmacology, Mech Ageing Dev, 126, 1019, 10.1016/j.mad.2005.03.024 · DOI
  43. Wisdom, 1999, c-Jun regulates cell cycle progression and apoptosis by distinct mechanisms, EMBO J, 18, 188, 10.1093/emboj/18.1.188 · DOI
  44. Woods, 2007, The cell cycle hypothesis of Alzheimer's disease: suggestions for drug development, Biochim Biophys Acta, 1772, 503, 10.1016/j.bbadis.2006.12.004 · DOI
  45. Xifró, 2006, N-methyl-d-aspartate blocks activation of JNK and mitochondrial apoptotic pathway induced by potassium deprivation in cerebellar granule cells, J Biol Chem, 281, 6801, 10.1074/jbc.M504571200 · DOI
  46. Yeste-Velasco, 2007, Glycogen synthase kinase-3 is involved in the regulation of the cell cycle in cerebellar granule cells, Neuropharmacology, 53, 295, 10.1016/j.neuropharm.2007.05.012 · DOI
  47. Zhang, 2007, Critical role of PTEN in the coupling between PI3K/Akt and JNK1/2 signaling in ischemic brain injury, FEBS Lett, 581, 495, 10.1016/j.febslet.2006.12.055 · DOI
  48. Zhu, 2007, Alzheimer disease, the two-hit hypothesis: an update, Biochim Biophys Acta, 1772, 494, 10.1016/j.bbadis.2006.10.014 · DOI
  49. Zhu, 2004, Alzheimer's disease: the two-hit hypothesis, Lancet Neurol, 3, 219, 10.1016/S1474-4422(04)00707-0 · DOI

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Metadata

Authors
Yeste-Velasco, M., Folch, J., Casadesús, G., Smith, M. A., Pallàs, M., & Camins, A.
Affiliations
  • Universitat Rovira i Virgili (ES)
  • Case Western Reserve University (US)
  • Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
Corresponding author
Camins, A.
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
2009-03
Volume
159
Issue
3
Pages
1135-1147
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/j.neuroscience.2009.01.035
OpenAlex
W2058774033
Cited by
31
References
0
Citations by year
2025: 1 · 2022: 1 · 2020: 1 · 2019: 1 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 4 · 2012: 5
FWCI
1.88
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Neuroscience › Neurology › Neuroprotection in Cerebral Ischemia
Keywords
SP600125, c-Jun NH2-terminal kinase, neuroprotection, potassium deprivation, apoptosis, cerebellar granule cells, AKT pathway, PI3K/Akt signaling, GSK3β, cyclin-dependent kinase 5, p35, cell cycle re-entry, retinoblastoma protein phosphorylation, FOXO1, CREB, neurodegenerative diseases
MeSH terms
Forkhead Box Protein O1, Glycogen Synthase Kinase 3 beta, Animals, Anthracenes, Cell Cycle, Cells, Cultured, Cerebellum, Chromones, Enzyme Inhibitors, Morpholines, Nerve Tissue Proteins, Phosphotransferases, Potassium, Signal Transduction, Rats, Sprague-Dawley, Apoptosis, Cyclic AMP Response Element-Binding Protein, Oxidative Stress, Neuroprotective Agents, Glycogen Synthase Kinase 3, JNK Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-akt, Cyclin-Dependent Kinase 5, Rats, Forkhead Transcription Factors

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