The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Protein Kinase C-mediated Neuroprotective Action of (-)-epigallocatechin-3-gallate against $A{\beta}_{1-42}$-induced Apoptotic Cell Death in SH-SY5Y Neuroblastoma Cells

  • Jang, Su-Jeong (Department of Physiology, Chonnam National University Medical School) ;
  • You, Kyoung-Wan (Department of Physiology, Chonnam National University Medical School) ;
  • Kim, Song-Hee (Department of Physiology, Chonnam National University Medical School) ;
  • Park, Sung-Jun (Department of Physiology, Chonnam National University Medical School) ;
  • Jeong, Han-Seong (Department of Physiology, Chonnam National University Medical School) ;
  • Park, Jong-Seong (Department of Physiology, Chonnam National University Medical School)
  • Published : 2007.10.31
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Abstract

The neurotoxicity of amyloid $\beta(A\beta)$ is associated with an increased production of reactive oxygen species and apoptosis, and it has been implicated in the development of Alzheimer's disease. While(-)-epigallocatechin-3-gallate(EGCG) suppresses $A\beta$-induced apoptosis, the mechanisms underlying this process have yet to be completely clarified. This study was designed to investigate whether EGCG plays a neuroprotective role by activating cell survival system such as protein kinase C(PKC), extracellular-signal-related kinase(ERK), c-Jun N-terminal kinase(JNK), and anti-apoptotic and pro-apoptotic genes in SH-SY5Y human neuroblastoma cells. One ${\mu}M\;A{\beta}_{1-42}$ decreased cell viability, which was correlated with increased DNA fragmentation evidenced by DAPI staining. Pre-treatment of SH-SY5Y neuroblastoma cells with EGCG($1{\mu}M$) significantly attenuated $A{\beta}_{1-42}$-induced cytotoxicity. Potential cell signaling candidates involved in this neuroprotective effects were further examined. EGCG restored the reduced PKC, ERK, and JNK activities caused by $A{\beta}_{1-42}$ toxicity. In addition, gene expression analysis revealed that EGCG prevented both the $A{\beta}_{1-42}$-induced expression of a pro-apoptotic gene mRNA, Bad and Bax, and the decrease of an anti-apoptotic gene mRNA, Bcl-2 and Bcl-xl. These results suggest that the neuroprotective mechanism of EGCG against $A{\beta}_{1-42}$-induced apoptotic cell death includes stimulation of PKC, ERK, and JNK, and modulation of cell survival and death genes.

Keywords

References

  1. Ahmad N, Feyes DK, Nieminen AL, Agarwal R, Mukhtar H. Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells. J Natl Cancer Ins 89: 1881-1886, 1997
  2. Barinaga M. Missing Alzheimer's gene found. Science 269: 917- 918, 1995 https://doi.org/10.1126/science.7638610
  3. Bastianetto S, Yao ZX, Papadopoulos V, Quirion R. Neuroprotective effects of green and black teas and their catechin gallate esters against beta-amyloid-induced toxicity. Eur J Neurosci 23: 55-64, 2006 https://doi.org/10.1111/j.1460-9568.2005.04532.x
  4. Behl C, Davis JB, Lesley R, Schubert D. Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 77: 817-827, 1994
  5. Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME. Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and independent mechanisms. Science 286: 1358-1362, 1999 https://doi.org/10.1126/science.286.5443.1358
  6. Braak H, de Vos RA, Jansen EN, Bratzke H, Braak E. Neuropathological hallmarks of Alzheimer's and Parkinson's diseases. Prog Brain Res 117: 267-285, 1998 https://doi.org/10.1016/S0079-6123(08)64021-2
  7. Butterfield DA, Lauderback CM. Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Rad Biol Med 32: 1050-1060, 2002 https://doi.org/10.1016/S0891-5849(02)00794-3
  8. Choi YT, Jung CH, Lee SR, Bae JH, Baek WK, Suh MH, Park J, Park CW, Suh SI. The green tea polyphenol (-)-epigallocatechin gallate attenuates beta-amyloid-induced neurotoxicity in cultured hippocampal neurons. Life Sci 21: 603-614, 2001
  9. Copani A, Condorelli F, Caruso A, Vancheri C, Sala A, Giuffrida Stella AM, Canonico PL, Nicoletti F, Sortino MA. Mitotic signaling by beta-amyloid causes neuronal death. FASEB J 13: 2225-2234, 1999 https://doi.org/10.1096/fasebj.13.15.2225
  10. Dempsey EC, Newton AC, Mochly-Rosen D, Fields AP, Reyland ME, Insel PA, Messing RO. Protein kinase C isozymes and the regulation of diverse cell responses. Am J Physiol Lung Cell Mol Physiol 279: L429-L438, 2000
  11. Drake J, Link CD, Butterfield DA. Oxidative stress precedes fibrillar deposition of Alzheimer's disease amyloid beta-peptide (1-42) in a transgenic Caenorhabditis elegans model. Neurobiol Aging 24: 415-420, 2003 https://doi.org/10.1016/S0197-4580(02)00225-7
  12. Graham HN. Green tea composition, consumption, and polyphenol chemistry. Prev Med 21: 334-350, 1992 https://doi.org/10.1016/0091-7435(92)90041-F
  13. Han YS, Zheng WH, Bastianetto S, Chabot JG, Quirion R. Neuroprotective effects of resveratrol against beta-amyloidinduced neurotoxicity in rat hippocampal neurons: involvement of protein kinase C. Br J Pharmacol 141: 997-1005, 2004 https://doi.org/10.1038/sj.bjp.0705688
  14. Jiffar T, Kurinna S, Suck G, Carlson-Bremer D, Ricciardi MR, Konopleva M, Andreeff M, Ruvolo PP. PKC alpha mediates chemoresistance in acute lymphoblastic leukemia through effects on Bcl2 phosphorylation. Leukemia 18: 505-512, 2004 https://doi.org/10.1038/sj.leu.2403275
  15. Kim SY, Ahn BH, Kim J, Bae YS, Kwak JY, Min G, Kwon TK, Chang JS, Lee YH, Yoon SH, Min DS. Phospholipase C, protein kinase C, Ca 2+ /calmodulin-dependent protein kinase II, and redox state are involved in epigallocatechin gallate-induced phospholipase D activation in human astroglioma cells. Eur J Biochem 271: 3470-3480, 2004 https://doi.org/10.1111/j.0014-2956.2004.04242.x
  16. Kumazawa S, Kajiya K, Naito A, Saito H, Tuzi S, Tanio M, Suzuki M, Nanjo F, Suzuki E, Nakayama T. Direct evidence of interaction of a green tea polyphenol, epigallocatechin gallate, with lipid bilayers by solid-state nuclear magnetic resonance. Biosci Biotechnol Biochem 68: 1743-1747, 2004 https://doi.org/10.1271/bbb.68.1743
  17. Levites Y, Amit T, Youdim MBH, Mandel S. Involvement of protein kinase C activation and cell survival/cell cycle genes in green tea polyphenol (-)-epigallocatechin-3-gallate neuroprotective action. J Biol Chem 277: 30574-30580, 2002 https://doi.org/10.1074/jbc.M202832200
  18. Levites Y, Amit T, Mandel S, Youdim MBH. Neuroprotection and neurorescue against amyloid beta toxicity and PKC-dependent release of non-amyloidogenic soluble precusor protein by green tea polyphenol (-)-epigallocatechin-3-gallate. FASEB J 17: 952-954, 2003 https://doi.org/10.1096/fj.02-0881fje
  19. Levites Y, Youdim MBH, Maor G, Mandel S. Attenuation of 6-hydroxydopamine (6-OHDA)-induced nuclear factor-kappB (NF-kappaB) activation and cell death by tea extracts in neuronal cultures. Biochem Pharmacol 63: 21-29, 2002 https://doi.org/10.1016/S0006-2952(01)00813-9
  20. Lu DC, Soriano S, Bredesen DE, Koo SH. Caspase cleavage of the amyloid precursor protein modulates amyloid beta-protein toxicity. J Neurochem 87: 733-741, 2003 https://doi.org/10.1046/j.1471-4159.2003.02059.x
  21. Maher P. How protein kinase C activation protects nerve cells from oxidative stress-induced cell death. J Neurosci 21: 2929-2938, 2001 https://doi.org/10.1523/JNEUROSCI.21-09-02929.2001
  22. Mandel S, Maor G, Youdim MBH. Iron and alpha-synuclein in the substantia Nigra of MPTP-treated mice: effect of neuroprotective drugs R-apomorphine and green tea polyphenol (-)- epigallocatechin-3-gallate. J Mol Neurosci 24: 401-416, 2004 https://doi.org/10.1385/JMN:24:3:401
  23. Mandel S, Weinreb O, Amit T, Youdim MB. Cell signaling pathways in the neuroprotective actions of the green tea polyphenol (-)-epigallocatechin-3-gallate: implications for neurodegenerative diseases. J Neurochem 88: 1555-1569, 2004 https://doi.org/10.1046/j.1471-4159.2003.02291.x
  24. Masuda M, Suzui M, Weinstein IB. Effects of epigallocatechin- 3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines. Clin Cancer Res 7: 4220-4229, 2001
  25. Pan MH, Lin-Shiau SY, Ho CT, Lin JH, Lin JK. Suppression of lypopolysaccharide-induced nuclear factor kappaB activity by theaflavin- 3,3'-digallate from black tea and other polyphenols through downregulation of I-\kappaB kinase activity in macrophages. Biochem Pharmacol 59: 357-367, 2000 https://doi.org/10.1016/S0006-2952(99)00335-4
  26. Pizzi M, Sarnico I, Boroni F, Benarese M, Steimberg N, Mazzoleni G, Dietz GPH, Bähr M, Liou HC, Spano PF. NF-kappaB factor c-Rel mediates neuroprotection elicited by mGlu5 receptor agonists against amyloid beta-peptide toxicity. Cell Death Diff 12: 761-772, 2005 https://doi.org/10.1038/sj.cdd.4401598
  27. Reznichenko L, Amit T, Youdim MB, MandelS. Green tea polyphenol (-)-epigallocatechin-3-gallate induces neurorescue of longterm serum-deprived PC12 cells and promotes neurite outgrowth. J Neurochem 93: 1157-1167, 2005 https://doi.org/10.1111/j.1471-4159.2005.03085.x
  28. Ruvolo PP, Deng X, Carr BK, May WS. A functional role for mitochondrial protein kinase Calpha in Bcl2 phosphorylation and suppression of apoptosis. J Biol Chem 273: 25436-25442, 1998 https://doi.org/10.1074/jbc.273.39.25436
  29. Schroeter H, Spencer JP, Rice-Evans C, Williams RJ. Flavonoids protect neurons from oxidized low-density-lipoprotein-induced caspase-3. Biochem J 358: 547-557, 2001 https://doi.org/10.1042/0264-6021:3580547
  30. Selkoe DJ. Deciphering the genesis and fate of amyloid beta-protein yields novel therapies for Alzheimer's disease. J Clin Invest 110: 1375-1381, 2002 https://doi.org/10.1172/JCI0216783
  31. Singer CA, Figueroa-Masot MA, Batchelor RH, Dorsa DM. The mitogen-activated protein kinase pathway mediates estrogen neuroprotection after glutamate toxicity in primary cortical neurons. J Neurosci 19: 2455-2463, 1999 https://doi.org/10.1523/JNEUROSCI.19-07-02455.1999
  32. Sinha S, Lieberburg I. Cellular mechanisms of beta-amyloid production and secretion. Proc Natl Acad Sci USA 96: 11049-11053, 1999
  33. Sultana R, Ravagna A, Mohmmad-Abdul H, Calabrese V, Butterfield DA. Ferulic acid ethyl ester protects neurons against amyloid beta-peptide(1-42)-induced oxidative stress and neurotoxicity: relationship to antioxidant activity. J Neurochem 92:749-758, 2005 https://doi.org/10.1111/j.1471-4159.2004.02899.x
  34. Tremblay R, Hewitt K, Lesiuk H, Mealing G, Morley P, Durkin JP. Evidence that brain-derived neurotrophic factor neuroprotection is linked to its ability to reverse the NMDA-induced inactivation of protein kinase C in cortical neurons. J Neurochem 72: 102-111, 1999 https://doi.org/10.1046/j.1471-4159.1999.0720102.x
  35. Valerio A, Boroni F, Benarese M, Sarnico I, Ghisi V, Bresciani LG, Ferrario M, Borsani G, Spano P, Pizzi M. NF-kappaB pathway: a target for preventing beta-amyloid (Abeta)-induced neuronal damage and Abeta42 production. Eur J Neurosci 23: 1711-1720, 2006 https://doi.org/10.1111/j.1460-9568.2006.04722.x
  36. Vianna MR, Barros DM, Silva T, Choi H, Madche C, Rodrigues C, Medina JH, Izquierdo I. Pharmacological demonstration of the differential involvement of protein kinase C isoforms in short- and long-term memory formation and retrieval of one-trial avoidance in rats. Psychopharmacology (Berl) 150: 77-84, 2000 https://doi.org/10.1007/s002130000396
  37. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 24: 1326-1331, 1995
  38. Yamazaki T, Koo EH, Selkoe DJ. Trafficking of cell-surface amyloid beta-protein precursor. II. Endocytosis, recycling and lysosomal targeting detected by immunolocalization. J Cell Sci 109: 999-1008, 1996
  39. Yang E, Zha J, Jockel J, Boise LH, Thompson CB, Korsmeyer SJ. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell 27: 285-291, 1995
  40. Yatin SM, Varadarajan S, Link CD, Butterfield DA. In vitro and in vivo oxidative stress associated with Alzheimer's amyloid beta-peptide (1-42). Neurobiol Aging 20: 325-330, 1999 https://doi.org/10.1016/S0197-4580(99)00056-1
  41. Yu R, Jiao JJ, Duh JL, Gudehithlu K, Tan TH, Kong AN. Activation of mitogen-activated protein kinases by green tea polyphenols: potential signaling pathways in the regulation of antioxidantresponsive element-mediated phase II enzyme gene expression. Carcinogenesis 18: 451-456, 1997 https://doi.org/10.1093/carcin/18.2.451