title: Minocycline inhibits ICAD degradation and the NF-κB activation induced by 6-OHDA in PC12 cells.
abstract: 6-Hydroxydopamine (6-OHDA) is a neurotoxin that is commonly employed to induce lesions of the dopaminergic pathways to generating experimental models of Parkinson's disease (PD) in rodents. Antioxidant and anti-inflammatory therapy approaches have been the focus of attention in the treatment of neurodegenerative. PD and Alzheimer's diseases, and oxidative stress have been implicated in these diseases. In this study, we investigated the neuroprotective effects of minocycline and the signalling pathway that is possibly involved in a PC12 cell model of PD. The results indicated that 6-OHDA cytotoxicity was accompanied by an increment in lactate dehydrogenase (LDH) release, an increase in caspase-3 protein activity, an increase in ROS generation, MDA content and decrease in the SOD, CAT activities and cell viability. Moreover, treatment with 6-OHDA alone for 24h resulted in ICAD degradation, increased nuclear translocation of NF-κB, and increased p53 expression. However, pretreatment with minocycline (5, 10, 20 µM) for 24h significantly reduced LDH release, reduced caspase-3 protein production, reduced ROS production, MDA content and attenuated the decrease in SOD, CAT activities and cell viability. Additionally, minocycline (20 µM) markedly decreased the levels of cleaved ICAD protein, down-regulated p53 activity and inhibited the nuclear translocation of NF-κB. The neuroprotective effects of minocycline were attributable to its potent antioxidant activities, which prevented the nuclear translocation of NF-κB and the subsequent promotion of cell death. Therefore, the present study supports the notion that minocycline may be a promising neuroprotective agent for the treatment of Parkinson's disease.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; Key Laboratory of Bioactive Substances and Resources Unilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.
authors.forename: Bao-Ping
authors.initials: BP
authors.lastname: Jiang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Le
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; Key Laboratory of Bioactive Substances and Resources Unilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China. Electronic address: ljxu@implad.ac.cn.
authors.forename: Li-Jia
authors.initials: LJ
authors.lastname: Xu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; Key Laboratory of Bioactive Substances and Resources Unilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China.
authors.forename: Pei-Gen
authors.initials: PG
authors.lastname: Xiao
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D045162:Thiazolidinediones; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C575035:(Z)2-(5-(4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetic acid; D018663:Adrenergic Agents; D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D016159:Tumor Suppressor Protein p53; C109664:caspase-activated DNase inhibitor; D016627:Oxidopamine; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D053148:Caspase 3; D008911:Minocycline
keywords: 6-Hydroxydopamine; Minocycline; Nuclear factor-κB; Parkinson’s disease