title: 3,4,5-tri-O-caffeoylquinic acid inhibits amyloid β-mediated cellular toxicity on SH-SY5Y cells through the upregulation of PGAM1 and G3PDH.
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.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8572, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Miyamae
authors.forename: Junkyu
authors.initials: J
authors.lastname: Han
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sasaki
authors.forename: Mika
authors.initials: M
authors.lastname: Terakawa
authors.forename: Hiroko
authors.initials: H
authors.lastname: Isoda
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Shigemori