title: Bumetanide-induced NKCC1 inhibition attenuates oxygen-glucose deprivation-induced decrease in proliferative activity and cell cycle progression arrest in cultured OPCs via p-38 MAPKs.
abstract: The Na-K-Cl co-transporter 1 (NKCC1; a member of the cation-chloride co-transporter family) mediates the coupled movement of Na(+) and/or K(+) with Cl(-) across the plasma membrane of cells (Haas and Forbush, 2000, Annu. Rev. Physiol., 62, 515-534; Russell, 2000, Physiol. Rev., 80, 211-276). Although it acts as an important regulator of cell volume, secretion, and modulator of cell apoptosis and proliferation (Chen et al., 2005, J. Cereb. Blood Flow Metab., 25, 54-66; Kahle et al., 2008, Nat. Clin. Pract. Neurol., 4, 490-503; Kidokoro et al., 2014, Am. J. Physiol. Ren. Physiol., 306, F1155-F1160; Wang et al., 2011, Cell. Physiol. Biochem., 28, 703-714), NKCC1׳s effects on oligodendrocyte precursor cells (OPCs) have not been characterized. The aim of this study was to investigate whether and to what extent inhibition of NKCC1 alters oxygen glucose deprivation (OGD)-induced cell cycle progression. In the present study, we demonstrated that inhibition of NKCC1 with bumetanide attenuates the decrease in OGD-induced DNA synthesis in cultured OPCs. Western blots showed that NKCC1 inhibition led to an increased expression of cyclin D1, CDK 4, and cyclin E in OGD-treated cells. Furthermore, our results showed bumetanide attenuated the decrease in OGD-induced proliferation and arrest of cell cycle progression via the P-38 MAPK signaling cascade. Thus, NKCC1 plays important roles in the proliferation of OPCs under OGD-induced stress.
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Peicai
authors.initials: P
authors.lastname: Fu
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China; Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan 430030, PR China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China; Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan 430030, PR China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China; Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan 430030, PR China. Electronic address: wwang@vip.126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D015687:Cell Hypoxia; D049109:Cell Proliferation / Q000187:drug effects; D005947:Glucose / Q000172:deficiency / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism / Q000502:physiology*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013312:Stress, Physiological; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C578879:Slc12a2 protein, rat; D049994:Sodium Potassium Chloride Symporter Inhibitors; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose
keywords: Cell cycle; Na–K–Cl co-transporter 1 (NKCC1); OPCs; Oxygen/glucose deprivation (OGD)