title: Cell cycle regulation of DNA polymerase beta in rotenone-based Parkinson's disease models.
abstract: In Parkinson's disease (PD), neuronal cells undergo mitotic catastrophe and endoreduplication prior to cell death; however, the regulatory mechanisms remain to be defined. In this study, we investigated cell cycle regulation of DNA polymerase β (poly β) in rotenone-based dopaminergic cellular and animal models. Incubation with a low concentration (0.25 µM) of rotenone for 1.5 to 7 days resulted in a flattened cell body and decreased DNA replication during S phase, whereas a high concentration (2 µM) of rotenone exposure resulted in enlarged, multi-nucleated cells and converted the mitotic cycle into endoreduplication. Consistently, DNA poly β, which is mainly involved in DNA repair synthesis, was upregulated to a high level following exposure to 2 µM rotenone. The abrogation of DNA poly β by siRNA transfection or dideoxycytidine (DDC) treatment attenuated the rotenone-induced endoreduplication. The cell cycle was reactivated in cyclin D-expressing dopaminergic neurons from the substantia nigra (SN) of rats following stereotactic (ST) infusion of rotenone. Increased DNA poly β expression was observed in the substantia nigra pars compacta (SNc) and the substantia nigra pars reticulate (SNr) of rotenone-treated rats. Collectively, in the in vitro model of rotenone-induced mitotic catastrophe, the overexpression of DNA poly β promotes endoreduplication; in the in vivo model, the upregulation of DNA poly β and cell cycle reentry were also observed in the adult rat substantia nigra. Therefore, the cell cycle regulation of DNA poly β may be involved in the pathological processes of PD, which results in the induction of endoreduplication.
authors.affiliation: Department of Neurology, Affiliated Hospital of Binzhou Medical University, Binzhou City, Shandong Province, China.
authors.forename: Hongcai
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, Affiliated Hospital of Binzhou Medical University, Binzhou City, Shandong Province, China.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Zhentao
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Yangxin traditional Chinese medical hospital, Yangxin County, Binzhou City, Shandong Province, China.
authors.forename: Wansheng
authors.initials: W
authors.lastname: Lao
authors.affiliation: Department of Neurology, Affiliated Hospital of Binzhou Medical University, Binzhou City, Shandong Province, China.
authors.forename: Xizhi
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jinsha
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics; D059447:Cell Cycle Checkpoints; D016923:Cell Death / Q000187:drug effects; D019951:DNA Polymerase beta / Q000235:genetics*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D012402:Rotenone / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism
chemical_list: D012402:Rotenone; D019951:DNA Polymerase beta