Carnosic acid protects SH-SY5Y cells against 6-hydroxydopamine-induced cell death through upregulation of parkin pathway. (November 2016)

• Record Type: Journal Article
• Authors: Lin, Chia-Yuan; Tsai, Chia-Wen; Tsai, Chia-Wen
• Is Part Of: Neuropharmacology. Volume 110(2016) Part A
• Page Start: 109
• Page End: 117
• Publication Date: 2016-11
• Subjects: Carnosic acid -- Neuroprotection -- Parkin -- Ubiquitin-proteasomal system -- α-synuclein; CA carnosic acid -- DMSO dimethylsulfoxide -- 6-OHDA 6-hydroxydopamine -- PARP poly(ADP)-ribose polymerase -- PD Parkinson's disease -- PINK1 PTEN-induced putative kinase 1 -- UPS ubiquitin-proteasome system -- siRNA small interfering RNA -- YFP yellow fluorescent protein; Carnosic acid (PubChem CID: 65126) -- Penicillin Streptomycin (PubChem CID: 86591708) -- 6-Hydroxydopamine hydrobromide (PubChem CID: 176170) -- Dimethyl sulfoxide (PubChem CID: 679) -- Triton X-100 (PubChem CID: 5590) -- Tween 20 (PubChem CID: 443314) -- MG132 (PubChem CID: 462382); Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2016.04.017
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Parkin is a Parkinson's disease (PD)-linked gene that plays an important role in the ubiquitin-proteasome system (UPS). This study explored whether carnosic acid (CA) from rosemary protects against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity via upregulation of parkin in vivo and in vitro . We found that the reduction in proteasomal activity by 6-OHDA was attenuated in SH-SY5Y cells pretreated with 1 μM CA. Immunoblots showed that CA reversed the induction of ubiquitinated protein and the reduction of PTEN-induced putative kinase 1 (PINK1) and parkin protein in 6-OHDA-treated SH-SY5Y cells and rats. Moreover, in a transgenic OW13 Caenorhabditis elegans model of PD that expresses human α-synuclein in muscle cells, CA reduced α-synuclein accumulation in a dose-dependent manner. In cells pretreated with the proteasome inhibitor MG132, CA no longer reversed the 6-OHDA-mediated induction of cleavage of caspase 3 and poly(ADP)-ribose polymerase and no longer reversed the suppression of proteasome activity. When parkin expression was silenced by use of small interfering RNA, the ability of CA to inhibit apoptosis and induce proteasomal activity was significantly reduced. The reduction in 6-OHDA-induced neurotoxicity by CA was associated with the induction of parkin, which in turn upregulated the UPS and then decreased cell death. Highlights: CA increased parkin and decreased ubiquitinated proteins in 6-OHDA-treated SH-SY5Y cells and rats. CA prevented 6-OHDA-induced ubiquitin-proteasome system dysfunction and apoptosis in SH-SY5Y cells. Parkin is involved in the ability of CA to reverse the effects of 6-OHDA on proteasome dysfunction and apoptosis.