title: DCPIB, a specific inhibitor of volume-regulated anion channels (VRACs), inhibits astrocyte proliferation and cell cycle progression via G1/S arrest.
abstract: Volume-regulated anion channels (VRACs) are involved in regulating the proliferation and cell cycle progression of a number of cell types. However, little is known about its role on astrocyte proliferation, although numerous VRACs were reported to play important roles in astrocytic neurotransmitters release during swelling. In the present study, we demonstrated that VRAC inhibition by 4-(2-butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl) oxobutyric acid (DCPIB) can attenuate astrocyte proliferation and DNA synthesis in vitro. Simultaneously, Western blots showed that VRAC inhibition led to a decrease in CDK 4 and cyclin D1 expression accompanied with an increase in p27 expression, which caused the proliferating astrocytes arrested at the G1/S checkpoint. Furthermore, we showed that DCPIB-induced astrocyte proliferation inhibition was modulated through the ERK signaling cascade. These observations demonstrated that VRACs play essential roles in the proliferation of astrocyte.
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.forename: Xiang
authors.initials: X
authors.lastname: Luo
authors.forename: Wenjie
authors.initials: W
authors.lastname: Wei
authors.forename: Minjie
authors.initials: M
authors.lastname: Xie
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Yu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000838:Anions / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology; D003517:Cyclopentanes / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D007189:Indans / Q000494:pharmacology*; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D051381:Rats; D016196:S Phase / Q000187:drug effects
chemical_list: C443139:4-(2-butyl-6,7-dichlor-2-cyclopentyl-indan-1-one-5-yl)oxybutyric acid; D000838:Anions; D003517:Cyclopentanes; D007189:Indans; D007473:Ion Channels; D009419:Nerve Tissue Proteins