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https://doi.org/10.1038/s41419-018-1230-5
| Title: | DR-region of Na + /K + ATPase is a target to treat excitotoxicity and stroke | Authors: | Shi, M Cao, L Cao, X Zhu, M Zhang, X Wu, Z Xiong, S Xie, Z Yang, Y Chen, J Wong, P.T.H Bian, J.-S |
Keywords: | adenosine triphosphatase (potassium sodium) calcium glutamic acid protein interacting with protein kinase C adenosine triphosphatase (potassium sodium) AMPA receptor antibody glutamate receptor ionotropic, AMPA 2 glutamic acid peptide sodium calcium exchange protein animal cell animal tissue apoptosis Article brain cell culture brain tissue calcium cell level cell membrane cell viability cerebrovascular accident comparative study confocal microscopy controlled study endocytosis excitotoxicity immunoprecipitation infarct volume internalization middle cerebral artery occlusion mouse nerve cell plasticity nerve excitability neuroprotection nonhuman priority journal protein expression protein phosphorylation time-lapse microscopy Western blotting whole cell patch clamp animal brain cortex cerebrovascular accident chemistry disease model genetics metabolism nerve cell pathology Animals Antibodies Cerebral Cortex Disease Models, Animal Glutamic Acid Mice Neurons Peptides Receptors, AMPA Sodium-Calcium Exchanger Sodium-Potassium-Exchanging ATPase Stroke |
Issue Date: | 2019 | Publisher: | Nature Publishing Group | Citation: | Shi, M, Cao, L, Cao, X, Zhu, M, Zhang, X, Wu, Z, Xiong, S, Xie, Z, Yang, Y, Chen, J, Wong, P.T.H, Bian, J.-S (2019). DR-region of Na + /K + ATPase is a target to treat excitotoxicity and stroke. Cell Death and Disease 10 (1) : 6. ScholarBank@NUS Repository. https://doi.org/10.1038/s41419-018-1230-5 | Abstract: | Na + /K + ATPase (NKA) is important in maintaining cellular functions. We found that loss of NKA activities in NKA?1 +/? mice is associated with increased susceptibility to ischemic injuries following transient middle cerebral artery occlusion (tMCAO). This is corroborated by the neuroprotective effects of an antibody raised against an extracellular DR region ( 897 DVEDSYGQQWTYEQR 911 , sequence number as in rat) of NKA? subunit (DR-Ab) in both preventive and therapeutic settings. DR-Ab protects cortical neurons against glutamate-induced toxicity by stimulating activities of NKA and Na + /Ca 2+ exchanger (NCX), which resulted in accelerated Ca 2+ extrusion. DR-Ab also enhanced the association between NKA and GluR2 and therefore reduced the internalization of both proteins from membrane induced by glutamate toxicity. The mechanism appears to involve suppression of GluR2 phosphorylation through PKC?/PICK pathway. Our data indicate that DR-region of NKA may be a novel therapeutic target for drug development for the treatment of ischemic stroke. © 2018, The Author(s). | Source Title: | Cell Death and Disease | URI: | https://scholarbank.nus.edu.sg/handle/10635/174190 | ISSN: | 2041-4889 | DOI: | 10.1038/s41419-018-1230-5 |
| Appears in Collections: | Elements Staff Publications |
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