Abstract
Caffeoylquinic acid (CQA) is one of the phenylpropanoids found in a variety of natural resources and foods, such as sweet potatoes, propolis, and coffee. Previously, we reported that 3,5-di-O-caffeoylquinic acid (3,5-di-CQA) has a neuroprotective effect against amyloid-β (Aβ)-induced cell death through the overexpression of glycolytic enzyme. Additionally, 3,5-di-CQA administration induced the improvement of spatial learning and memory on senescence accelerated-prone mice (SAMP8). The aim of this study was to investigate whether 3,4,5-tri-O-caffeoylquinic acid (3,4,5-tri-CQA), isolated from propolis, shows a neuroprotective effect against Aβ-induced cell death on human neuroblastoma SH-SY5Y cells. To clarify the possible mechanism, we performed proteomics and real-time RT–PCR as well as a measurement of the intracellular adenosine triphosphate (ATP) level. These results showed that 3,4,5-tri-CQA attenuated the cytotoxicity and prevented Aβ-mediated apoptosis. Glycolytic enzymes, phosphoglycerate mutase 1 (PGAM1) and glyceraldehyde-3-phosphate dehydrogenase (G3PDH) were overexpressed in co-treated cells with both 3,4,5-tri-CQA and Aβ. The mRNA expression of PGAM1, G3PDH, and phosphoglycerate kinase 1 (PGK1), and intracellular ATP level were also increased in 3,4,5-tri-CQA treated cells. Taken together the findings in our study suggests that 3,4,5-tri-CQA shows a neuroprotective effect against Aβ-induced cell death through the upregulation of glycolytic enzyme mRNA as well as ATP production activation.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10616-011-9341-1/MediaObjects/10616_2011_9341_Fig1_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10616-011-9341-1/MediaObjects/10616_2011_9341_Fig2_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10616-011-9341-1/MediaObjects/10616_2011_9341_Fig3_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10616-011-9341-1/MediaObjects/10616_2011_9341_Fig4_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10616-011-9341-1/MediaObjects/10616_2011_9341_Fig5_HTML.gif)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10616-011-9341-1/MediaObjects/10616_2011_9341_Fig6_HTML.gif)
Similar content being viewed by others
References
Atamna H, Frey WHII (2007) Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer’s disease. Mitochondrion 7:297–310
Boyd-Kimball D, Sultana R, Poon HF, Lynn BC, Casamenti F, Pepeu G, Klein JB, Butterfield DA (2005) Proteomic identification of proteins specifically oxidized by intracerebral injection of amyloid β-peptide (1–42) into rat brain: implications for Alzheimer’s disease. Neuroscience 132:313–324
Butterfield DA, Boyd-Kimball D (2005) The critical role of methionine 35 in Alzheimer’s amyloid beta-peptide (1–42)-induced oxidative stress and neurotoxicity. Biochim Biophys Acta 1703:149–156
Canback B, Andersson SGE, Kurland CG (2002) The global phylogency of glycolytic enzymes. Proc Natl Acad Sci USA 99:6097–6102
Cardoso SM, Santos S, Swerdlow RH, Oliveira CR (2001) Functional mitochondria are required for amyloid beta-mediated neurotoxicity. FASEB J 15:1439–1441
Castegna A, Thongboonkerd V, Klein JB, Lynn B, Markesbery WR, Butterfield DA (2003) Proteomic identification of nitrated proteins in Alzheimer’s disease brain. J Neurochem 85:1394–1401
Clifford MN, Wu W, Kirkpatrick J, Kuhnert N (2007) Profiling the chlorogenic acids and other caffeic acid derivatives of herbal chrysanthemum by LC-MS. J Agric Food Chem 55:929–936
Farah A, Paulis TD, Trugo LC, Martin PR (2005) Effect of roasting on the formation of chlorogenic acid lactone in coffee. J Agric Food Chem 53:1505–11513
Ferrer I (2009) Altered mitochondria, energy metabolism, voltage-dependent anion channel, and lipid rafts converge to exhaust neurons in Alzheimer’s disease. J Bioenerg Biomembr 41:425–431
Han J, Miyamae Y, Shigemori H, Isoda H (2010) Neuroprotective effect of 3, 5-di-O-caffeoylquinic acid on SH-SY5Y cells and SAMP8 mice through the up-regulation of PGK1. Neuroscience 169:1039–1045
Isoda H, Talorete TPN, Han J, Nakamura K (2006) Expresion of galectin-3, glutathione S-transferase A2 and peroxiredoxin-1 by nonyphenol-incubated Caco-2 cells and reduction in transepithelial electrical resistance by nonyphenol. Toxicol In Vitro 20:63–70
Kim JW, Dang CV (2005) Multifaceted roles of glycolytic enzymes. Trends Biochem Sci 30:142–150
Kimura Y, Okuda H, Okuda H, Hatano T, Agata I, Arichi S (1985) Inhibitory effects of caffeoylquinic acids on histamine release from rat peritoneal mast cells. Chem Pharm Bull 33:690–696
Kondoh H, Lleonart ME, Gil J, Wang J, Degan P, Peters G, Martinez D, Carnero A, Beach D (2005) Glycolytic enzymes can modulate cellular life span. Cancer Res 65:177–185
Korolainen MA, Goldsteins G, Nyman TA, Alafuzoff I, Pirttila T (2005) Proteomic analysis of glial fibrillary acidic protein in Alzheimer’s disease and aging brain. Neurobiol Dis 20:858–870
Korolainen MA, Goldsteins G, Nyman TA, Alafuzoff I, Koistinaho J, Pirttilä T (2006) Oxidative modification of proteins in the frontal cortex of Alzheimer’s disease brain. Neurobiol Aging 27:42–53
Kurata R, Adachi M, Yamakawa O, Yoshimoto M (2007) Growth suppression of human cancer cells by polyphenolics from sweetpotato (Ipomoea batatas L.) leaves. J Agric Food Chem 55:185–190
Liu X, Shibata T, Hisaka S, Osawa T (2009) Astaxanthin inhibits reactive oxygen species-mediated cellular toxicity in dopaminergic SH-SY5Y cells via mitochondria-targeted protective mechanism. Brain Res 1254:18–27
Matharu B, Gibson G, Parsons R, Huckerby TN, Moore SA, Cooper LJ, Millichamp R, Allsop D, Austen B (2009) Galantamine inhibits β-amyloid aggregation and cytotoxicity. J Neurol Sci 280:49–58
Matsui T, Ebuchi S, Fujise T, Abesundara KJ, Doi S, Yamada H, Matsumoto K (2004) Strong anti hyperglycemic effects of water-soluble fraction of Brazilian propolis and its bioactive constituent, 3, 4, 5-tri-O-caffeoylquinic acid. Biol Pharm Bull 27:1797–1803
Mazzolaa JL, Sirover MA (2003) Subcellular alternation of glyceraldehyde-3-phosphate dehydrogenase in Alzheimer’s disease fibroblasts. J Neurosci Res 71:279–285
Merfort I (1992) Caffeoylquinic acids from flowers of Arnica Montana and Arnica chamissonis. Phytochemistry 31:2111–2113
Miranda S, Opazo C, Larrondo LF, Munoz FJ, Ruiz F, Leighton F, Inestrosa NC (2000) The role of oxidative stress in the toxicity induced by amyloid β-peptide in Alzheimer’s disease. Prog Neurobiol 62:633–648
Mishima S, Inoh Y, Narita Y, Ohta S, Sakamoto T, Araki Y, Suzuki K, Akao Y, Nozawa Y (2005) Identification of caffeoylquinic acid derivatives from Brazilian propolis as constituents involved in induction of granulocytic differentiation of HL-60 cells. Bioorg Med Chem 13:5814–5818
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity. Anal Biochem 65:55–63
Qi XL, **u J, Shan KR, **ao Y, Gu R, Liu RY, Guan ZZ (2005) Oxidative stress induced by beta-amyloid peptide1–42 is involved in the altered composition of cellular membrane lipids and the decreased expression of nicotinic receptors in human SH-SY5Y neuroblastoma cells. Neurochem Int 46:613–621
Ramassamy C, Averill D, Beffert U, Bastianetto S, Theroux L, Lussier-Cacan S, Chon JS, Christen Y, Davignon J, Quirion R, Poirier J (1999) Oxidative damage and protection by antioxidants in the frontal cortex of Alzheimer’s disease is related to the apolipoprotein E genotype. Free Radic Biol Med 27:544–553
Reed T, Perluigi M, Sultana R, Pierce WN, Klein JB, Turner DM, Coccia R, Markesbery WR, Butterfield DA (2008) Redox proteomic identification of 4-Hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: insight into the role lipid peroxidation in the progression and pathogenesis of Alzheimer’s disease. Neurobiol Dis 30:107–120
Shi C, Zhao L, Zhu B, Li Q, Yew DT, Yao Z, Xu J (2009) Protective effects of Ginkgo biloba extract (EGb761) and its constituents quercetin and ginkgolide B against β-amyloid peptide-induced toxicity in SH-SY5Y cells. Chem Biol Interact 181:115–123
Sirover MA (1999) New insights into an old protein: the functional diversity of mammalian glyceraldehyde-3-phosphate dehydrogenase. Biochem Biophys Acta 1432:159–184
Sultana R, Boyd-Kimball D, Poon HF, Cai J, Pierce WM, Klein JB, Merchantt M, Markesbery WR, Butterfield DA (2006) Redox proteomics identification of oxidized proteins in Alzheimer’s disease hippocampus and cerebellum: an approach to understand pathological and biochemical alternations in AD. Neurobiol Aging 27:1564–1576
Wang H, Xu Y, Yan J, Zhao X, Sun X, Zhang Y, Guo J, Zhu C (2009) Acteoside protects human neuroblastoma SH-SY5Y cells against β-amyloid-induced cell injury. Brain Res 1283:139–147
Yang JL, Weissman L, Bohr VA, Mattson MP (2008) Mitochondrial DNA damage and repair in neurodegenerative disorders. DNA Repair 7:1110–1120
Yoshimoto M, Yahara S, Okuno S, Islam MS, Ishiguro K, Yamakawa O (2002) Antimutagenicity of mono, di, and tri caffeoylquinic acid derivatives isolated from sweetpotato (Ipomoea batatas L.) leaf. Biosci Biotechnol Biochem 66:2336–2441
Zheng L, Roeder RG, Luo YS (2003) Phase activation of the histone H2B promoter by OCA-S, a coactivator complex that contains GAPDH as a key component. Cell 114:255–266
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Miyamae, Y., Han, J., Sasaki, K. et al. 3,4,5-tri-O-caffeoylquinic acid inhibits amyloid β-mediated cellular toxicity on SH-SY5Y cells through the upregulation of PGAM1 and G3PDH. Cytotechnology 63, 191–200 (2011). https://doi.org/10.1007/s10616-011-9341-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10616-011-9341-1