title: Clathrin-Dependent Uptake of Paraquat into SH-SY5Y Cells and Its Internalization into Different Subcellular Compartments.
abstract: The herbicide paraquat (PQ) is an exogenous toxin that allows the selective activation of dopaminergic neurons in the mesencephalon to induce injury and also causes its apoptosis in vitro. However, uptake mechanisms between PQ and neurons remain elusive. To address this issue, we undertook a study of PQ endocytosis in a dopaminergic SH-SY5Y cell line as well as explored the subsequent subcellular location and potential functional analysis of PQ. The PQ was found to bind the SH-SY5Y cell membrane and then became internalized via a clathrin-dependent pathway. PQ was internalized by many subcellular organelles in a time- and dose-dependent manner. Interestingly, the taken up PQ and secretogranin III (SCG3), which became dysregulated with PQ treatment that induced SH-SY5Y apoptosis in our previous study, colocalized in cytoplasmic vesicles. Taken together, our findings indicate that PQ is endocytosed by SH-SY5Y cells and that its multiple, subcellular localizations indicate PQ may potentially be involved in subcellular-level functions. More importantly, PQ distributing preferentially into SCG3-positive vesicles demonstrates its selective targeting which may affect SCG3 and cargoes carried by SCG3-positive vesicles. Therefore, it is reasonable to infer that PQ toxic insults may potentially interfere with neurotransmitter storage and transport associated with secretory granules.
authors.affiliation: School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, People's Republic of China.|Department of Forensic Medicine, Baotou Medical University, Baotou, People's Republic of China.
authors.forename: Fengrui
authors.initials: F
authors.lastname: Li
authors.affiliation: School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, People's Republic of China.|Department of Forensic Medicine, Hebei North University, Zhangjiakou, People's Republic of China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Tian
authors.affiliation: School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, People's Republic of China.
authors.forename: Xiaoni
authors.initials: X
authors.lastname: Zhan
authors.affiliation: School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, People's Republic of China.
authors.forename: Baojie
authors.initials: B
authors.lastname: Wang
authors.affiliation: School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Ding
authors.affiliation: School of Forensic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, People's Republic of China. hpang@cmu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Pang
mesh_terms: D001324:Autoantigens / Q000378:metabolism; D037281:Calnexin / Q000378:metabolism; D002452:Cell Count; D045744:Cell Line, Tumor; D002864:Chromogranins / Q000378:metabolism; D002966:Clathrin / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects*; D000077614:Golgi Matrix Proteins; D006801:Humans; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D010269:Paraquat / Q000378:metabolism / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects* / Q000378:metabolism*; D013997:Time Factors; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D001324:Autoantigens; D002864:Chromogranins; D002966:Clathrin; D000077614:Golgi Matrix Proteins; C450721:Golgi complex autoantigen, 97-kDa; D052118:Lysosomal-Associated Membrane Protein 1; D033921:Vesicular Transport Proteins; C093846:early endosome antigen 1; C506167:secretogranin III; D037281:Calnexin; D010269:Paraquat
keywords: Endocytosis; Internalization; Paraquat; SCG3; SH-SY5Y