title: HCdc14A is involved in cell cycle regulation of human brain vascular endothelial cells following injury induced by high glucose, free fatty acids and hypoxia.
abstract: Cell cycle processes play a vital role in vascular endothelial proliferation and dysfunction. Cell division cycle protein 14 (Cdc14) is an important cell cycle regulatory phosphatase. Previous studies in budding yeast demonstrated that Cdc14 could trigger the inactivation of mitotic cyclin-dependent kinases (Cdks), which are required for mitotic exit and cytokinesis. However, the exact function of human Cdc14 (hCdc14) in cell cycle regulation during vascular diseases is yet to be elucidated. There are two HCdc14 homologs: hCdc14A and hCdc14B. In the current study, we investigated the potential role of hCdc14A in high glucose-, free fatty acids (FFAs)-, and hypoxia-induced injury in cultured human brain vascular endothelial cells (HBVECs). Data revealed that high glucose, FFA, and hypoxia down-regulated hCdc14A expression remarkably, and also affected the expression of other cell cycle-related proteins such as cyclin B, cyclin D, cyclin E, and p53. Furthermore, the combined addition of the three stimuli largely blocked cell cycle progression, decreased cell proliferation, and increased apoptosis. We also determined that hCdc14A was localized mainly to centrosomes during interphase and spindles during mitosis using confocal microscopy, and that it could affect the expression of other cycle-related proteins. More importantly, the overexpression of hCdc14A accelerated cell cycle progression, enhanced cell proliferation, and promoted neoplastic transformation, whereas the knockdown of hCdc14A using small interfering RNA produced the opposite effects. Therefore, these findings provide novel evidence that hCdc14A might be involved in cell cycle regulation in cultured HBVECs during high glucose-, FFA-, and hypoxia-induced injury.
authors.affiliation: Department of Neurology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai 200011, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Geriatric Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: zhg7376@163.com.
authors.forename: Houguang
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of General Medicine, Ouyang Hospital, Hongkou District, Shanghai, China.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Emergency Neurology, The Affiliated Hospital of Medical College Qingdao University, Qingdao 266100, China.
authors.forename: Zhuangli
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Endocrine, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Geriatric Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Geriatric Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Endocrine, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Renming
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: dongqiangmd@hotmail.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D002453:Cell Cycle / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016213:Cyclins / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D018613:Microscopy, Confocal; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases; D034741:RNA, Small Interfering / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016213:Cyclins; D005230:Fatty Acids, Nonesterified; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D010744:Phosphoric Monoester Hydrolases; C120902:CDC14A protein, human; D017027:Protein Tyrosine Phosphatases; D005947:Glucose
keywords: Cell cycle; Free fatty acids; High glucose; Human brain vascular endothelial cells; Human cell division cycle protein 14A; Hypoxia