title: Interplay of salicylaldehyde, lysine, and M2+ ions on α-synuclein aggregation: cancellation of aggregation effects and determination of salicylaldehyde neurotoxicity.
abstract: In this study, α-synuclein was treated in vitro with salicylaldehyde (SA), lysine (lys) and M(n+) (Cu(2+) or Zn(2+)) in various ratios. SA induced aggregation of α-syn in the ratio of 1:500 (α-syn:SA) after incubation (pH 7.4, PBS buffer, 16-24h). Free lys can thus scavenge SA, inhibiting the aggregation of α-syn up to ∼63% (α-syn:SA:lys=1:1000:5000). When Cu(2+) and Zn(2+) are added to SA and α-syn, protein aggregation is induced. In the case of Zn(2+), the aggregation of α-syn increased to 74% (ratio=1:1000:50). Fluorescence studies support the production of protein-bound Zn(2+)-salicylaldimine species. For Cu(2+), aggregation of α-syn was shown (138%). Thus, possible protective or inducing effects of lys, Cu(2+) and Zn(2+) may exist with α-syn. α-Syn, SA and Cu(2+) can undergo complexation (fluorescence, CD and MALDI data). Cellular toxicity of SA (700μM), Zn(2+) (700μM) and Cu(2+) (700μM) on SH-SY5Y (1×10(5) cells) showed 9.8%, 38.0% and 14.4% compared to control values. Combinations showed more severe toxicities: 71.9% and 93.1% for SA (70μM)+Cu(2+) (700μM) and SA (70μM)+Zn(2+) (700μM), respectively, suggesting complexation itself may be toxic.
authors.affiliation: Molecular Logic Gate Laboratory, Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), 373-1 Guseong-dong, Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Yonghwang
authors.initials: Y
authors.lastname: Ha
authors.forename: Hyunjeong
authors.initials: H
authors.lastname: Liew
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Park
authors.forename: Kibong
authors.initials: K
authors.lastname: Kim
authors.forename: Yoo-Hun
authors.initials: YH
authors.lastname: Suh
authors.forename: David G
authors.initials: DG
authors.lastname: Churchill
mesh_terms: D000447:Aldehydes / Q000378:metabolism / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003300:Copper / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism* / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D015032:Zinc / Q000378:metabolism* / Q000633:toxicity; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D051844:alpha-Synuclein; C013243:salicylaldehyde; D008345:Manganese; D003300:Copper; D015032:Zinc; D008239:Lysine