Session Information
Date: Tuesday, June 6, 2017
Session Title: Parkinson's Disease: Pathophysiology
Session Time: 1:45pm-3:15pm
Location: Exhibit Hall C
Objective: To find the potent drug for prevention of PD, we screened with above 1000 drugs in the PQ treated cells which currently used drug in clinics and hospitals. Among those drugs, chloramphenicol (CP) showed most powerful inhibitory effect.
Background: Paraquat (PQ), an herbicide regarding as an environmental factor for Parkinson’s disease (PD) occurrence, induce dopaminergic neuronal loss via inhibition of mitochondrial complex I and III. Most patients of PQ-induced PD is affected by chronic exposure and need to preventional strategy for modulation of the disease progression.
Methods: We assessed the change of mitochondria complex expression using real time PCR, western blotting and immunohistochemistry in dopaminergic neuronal SN4741, mitochondrial DNA-depleted Rho cell and primary dopaminergic neuron . And to evaluate the function of mitochondria, we measured mitochondrial oxygen consumption rate using Seahorse bioscience XF24 analyzer. Also, we confirmed the ameliorate effect of CP in MPTP induced parkinson’s disease mouse model.
Results: Administration of PQ after CP pretreatment has more increased cell viability in SN4741 cells and primary cultured dopaminergic neurons from rat than control group. Furthermore, reactive oxygen species (ROS) production with PQ treatment also reduced by CP pretreatment which imply the mitochondrial complex I as a target of CP. Decreased activity of mitochondrial complex I by reducing synthesis of ND1 protein with CP treatment lowered the PQ-recycling, which is mechanism of ROS production, resulting prevention of cell death and those CP effect did not observed on the Rotenone pretreatment and Rho cells. Consistent with in vitro and ex vivo results, MPTP treated mice has also ameliorate the dopaminergic neuronal cell loss and glial reactivation with CP pretreatment.
Conclusions: Our finding indicate that inhibitory action of mitochondrial complex I with CP treatment for protecting the dopaminergic neurons may provide a presentational strategy in prevention of neurotoxin induced PD.
References: Kwon, H. J. et al. DJ-1 mediates paraquat-induced dopaminergic neuronal cell death. Toxicology letters 202, 85-92, doi:10.1016/j.toxlet.2011.01.018 (2011).
To cite this abstract in AMA style:
S.J. Kim, J. Han, Y. Jang, J. Kim, M.J. Lee, I. Ryu, X. Ju, M.J. Ryu, W. Chung, J.Y. Heo. Inhibition of mitochondrial complex I synthesis by chloramphenicol mitigates dopaminergic neuronal cell loss in PQ-induced parkinsonism [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/inhibition-of-mitochondrial-complex-i-synthesis-by-chloramphenicol-mitigates-dopaminergic-neuronal-cell-loss-in-pq-induced-parkinsonism/. Accessed May 17, 2025.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/inhibition-of-mitochondrial-complex-i-synthesis-by-chloramphenicol-mitigates-dopaminergic-neuronal-cell-loss-in-pq-induced-parkinsonism/