https://scholars.lib.ntu.edu.tw/handle/123456789/519910
標題: | Dose-dependent folic acid and memantine treatments promote synergistic or additive protection against Aβ(25-35) peptide-induced apoptosis in SH-SY5Y cells mediated by mitochondria stress-associated death signals | 作者: | TA-FU CHEN Tang M.-C. Chou C.-H. MING-JANG CHIU Huang R.-F.S. |
公開日期: | 2013 | 出版社: | Elsevier Ltd | 卷: | 62 | 起(迄)頁: | 538-547 | 來源出版物: | Food and Chemical Toxicology | 摘要: | Increased dietary folic acid (FA) is associated with reduced risks of Alzheimer's disease (AD). The AD drug memantine (Mn) has had limited therapeutic effects for the treatment of patients with moderate to severe AD. This study investigated whether and the underlying mechanisms by which the combination of Mn and FA may have synergistic or additive effects in protecting against amyloid-β(25-35) peptide (Aβ)-induced neurocytotoxicity. Aβ treatment of human neuroblastoma SH-SY5Y cells significantly induced a 6-fold increase of apoptotic cells compared with the Aβ-untreated group. Preincubation of Aβ-exposed cells with FA (500μM) or Mn (20μM) caused a 22% and 10% reduction of apoptotic cells, respectively, whereas the combo-treatments at such doses synergistically alleviated Aβ-induced apoptosis by 60% (P<0.05). The apoptotic protection by the combo-treatments coincided with attenuating Aβ-elicited mitochondrial (mt) membrane depolarization and abolishing Aβ-induced mt cytochrome c release to the cytosol. Increased levels of FA at 1000μM in combination with 20μM Mn exerted an additive protection against Aβ(25-35)-induced-apoptosis as compared to the isolate Mn group (P<0.05). The combo-treatments reversed Aβ-elicited mt membrane depolarization, attenuated Aβ-elicited mt cytochrome c release to the cytosol, and diminished Aβ-promoted superoxide generation. The apoptotic-protection by such combo-treatments was partially abolished by carbonyl cyanide 3-chlorophenylhydrazone (mt membrane potential uncoupler) and sodium azide (mt cytochrome c oxidase inhibitor). Taken together, the data demonstrated that dose-dependent FA and Mn synergistically or additively protected SH-SY5Y cells against Aβ-induced apoptosis, which was partially, if not completely, mediated by mt stress-associated death signals. ? 2013 Elsevier Ltd. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84885357557&doi=10.1016%2fj.fct.2013.09.015&partnerID=40&md5=c2d7efc25c36a786e153b0be3633cb42 https://scholars.lib.ntu.edu.tw/handle/123456789/519910 |
ISSN: | 0278-6915 | DOI: | 10.1016/j.fct.2013.09.015 | SDG/關鍵字: | amyloid beta protein[25-35]; caspase 3; cytochrome c; folic acid; memantine; apoptosis; article; calcium cell level; cell membrane depolarization; concentration response; controlled study; cytoplasm; drug efficacy; drug potentiation; human; human cell; mitochondrion; neuroblastoma cell; neuroprotection; neurotoxicity; protein cleavage; protein secretion; 2′,7′-dichlorodihydrofluorescin diacetate; 2′,7′-dichlorofluorescin; AD; Alzheimer's disease; amyloid-β; Amyloid-β((25-35)) peptide; annexin-V-FITC; Apoptosis; AV; Aβ((25-35)); carbonyl cyanide 3-chlorophenylhydrazone; CCCP; COX; cytochrome c oxidase; DCF; DCFH-DA; FA; Folate; folic acid; HE; hydroethidine; Memantine; memantine; mitochondria; Mitochondrial death signal; Mn; Mt; N-acetyl-L-cysteine; N-methyl-D-aspartate; NAC; NMDA; PI; propidium iodide; Amyloid beta-Peptides; Apoptosis; Calcium Signaling; Cell Line, Tumor; Cytochromes c; Dantrolene; Dose-Response Relationship, Drug; Drug Synergism; Folic Acid; Humans; Hydrazones; Memantine; Membrane Potential, Mitochondrial; Mitochondria; Neuroprotective Agents; Peptide Fragments; Reactive Oxygen Species |
顯示於: | 醫學系 |
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