title: Reynosin protects against neuronal toxicity in dopamine-induced SH-SY5Y cells and 6-hydroxydopamine-lesioned rats as models of Parkinson's disease: Reciprocal up-regulation of E6-AP and down-regulation of α-synuclein.
abstract: Aggregation of α-synuclein (ASYN) is considered a major determinant of neuronal loss in Parkinson's disease (PD). E6-associated protein (E6-AP), an E3 ubiquitin protein ligase, has been known to promote the degradation of α-synuclein. The aim of this study was to assess the effects of the sesquiterpene lactone reynosin on dopamine (DA)-induced neuronal toxicity and regulation of E6-associated protein and α-synuclein proteins in both in vitro and in vivo models of Parkinson's disease. Usi"ng flow cytometry and western blot analysis, we determined that reynosin significantly protected both against cell death from dopamine-induced toxicity in human neuroblastoma SH-SY5Y cells and against the loss of tyrosine hydroxylase (TH)-positive cells in 6-hydroxydopamine (6-OHDA)-lesioned rats (a rodent Parkinson's disease model system). In addition, reynosin made up-regulation of E6-associated protein expression and down-regulation of the over-expression of α-synuclein protein in both dopamine-treated SH-SY5Y cells and 6-hydroxydopamine-lesioned rats. These results suggest that the protective effect of reynosin against dopamine-induced neuronal cell death may be due to the reciprocal up-regulation of E6-associated protein and down-regulation of α-synuclein protein expression.
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea.
authors.forename: Ahrom
authors.initials: A
authors.lastname: Ham
authors.forename: Dong-Woo
authors.initials: DW
authors.lastname: Kim
authors.forename: Kyeong Ho
authors.initials: KH
authors.lastname: Kim
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Ki-Bong
authors.initials: KB
authors.lastname: Oh
authors.forename: Jongheon
authors.initials: J
authors.lastname: Shin
authors.forename: Woongchon
authors.initials: W
authors.lastname: Mar
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis*; D015854:Up-Regulation; D051844:alpha-Synuclein / Q000096:biosynthesis*
chemical_list: D018696:Neuroprotective Agents; D012717:Sesquiterpenes; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C016715:reynosin
keywords: 6-OHDA lesion; E6-associated protein; Neuroprotection; Parkinson's disease; Reynosin; α-Synuclein