Inhibition of WNK3 Kinase Signaling Reduces Brain Damage and Accelerates Neurological Recovery after Stroke

Stroke

Volumn 46, Issue 7, 2015, Pages 1956-1965

  Begum, Gulnaz ^a   Yuan, Hui ^a   Kahle, Kristopher T ^b,c   Li, Liaoliao ^a   Wang, Shaoxia ^a   Shi, Yejie ^a   Shmukler, Boris E ^d,e   Yang, Sung Sen ^f   Lin, Shih Hua ^f   Alper, Seth L ^d,e   Sun, Dandan ^a,g  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^b BOSTON CHILDREN S HOSPITAL   (United States)

^c Manton Center for Orphan Diseases   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

^e BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

^f TRI SERVICE GENERAL HOSPITAL   (Taiwan)

^g VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

bumetanide; KCC2 cotransporter; NKCC1 cotransporter; OSR1 kinase; SPAK Kinase

Indexed keywords

PROTEIN KINASE; PROTEIN KINASE WNK3; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; PROTEIN SERINE THREONINE KINASE; WNK3 PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD BRAIN BARRIER; BRAIN BLOOD FLOW; BRAIN DAMAGE; BRAIN EDEMA; BRAIN INFARCTION SIZE; BRAIN ISCHEMIA; BRAIN TISSUE; BRAIN WATER; CELL SURFACE; CEREBROVASCULAR ACCIDENT; CONTROLLED STUDY; CONVALESCENCE; CORPUS CALLOSUM; CYTOSOLIC FRACTION; DEMYELINATION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; EXTERNAL CAPSULE; FETUS; GENETIC ANALYSIS; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; MIDDLE CEREBRAL ARTERY OCCLUSION; MOUSE; NERVE CELL CULTURE; NEUROPROTECTION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OLIGODENDROCYTE PRECURSOR CELL; OLIGODENDROGLIA; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REOXYGENATION; SENSORIMOTOR FUNCTION; SIGNAL TRANSDUCTION; WHITE MATTER; 129 MOUSE; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; BRAIN INJURY; CELL CULTURE; DEFICIENCY; ENZYMOLOGY; FEMALE; KNOCKOUT MOUSE; MALE; NEUROLOGIC DISEASE; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; PREGNANCY; TRANSGENIC MOUSE;

ANIMALS; BRAIN INJURIES; CELLS, CULTURED; FEMALE; MALE; MICE; MICE, 129 STRAIN; MICE, KNOCKOUT; MICE, TRANSGENIC; NERVOUS SYSTEM DISEASES; PREGNANCY; PROTEIN-SERINE-THREONINE KINASES; RECOVERY OF FUNCTION; SIGNAL TRANSDUCTION; STROKE;

EID: 84941029569     PISSN: 00392499     EISSN: 15244628     Source Type: Journal    
DOI: 10.1161/STROKEAHA.115.008939     Document Type: Article

References (54)

1. Moskowitz MA, Lo EH, Iadecola C. The science of stroke: mechanisms in search of treatments. Neuron 2010;67:181-98.
2. Muir KW, Lees KR. Clinical experience with excitatory amino acid antagonist drugs. Stroke. 1995;26:503-513.
3. Leng T, Shi Y, Xiong ZG, Sun D. Proton-sensitive cation channels and ion exchangers in ischemic brain injury: new therapeutic targets for stroke? Prog Neurobiol. 2014;115:189-209. doi: 10.1016/j. pneurobio.2013.12.008.
4. Song M, Yu SP. Ionic regulation of cell volume changes and cell death after ischemic stroke. Transl Stroke Res. 2014;5:17-27. doi: 10.1007/s12975-013-0314-x.
5. Shah NH, Aizenman E. Voltage-gated potassium channels at the crossroads of neuronal function, ischemic tolerance, and neurodegeneration. Transl Stroke Res. 2014;5:38-58. doi: 10.1007/s12975-013-0297-7.
6. Simard JM, Kent TA, Chen M, Tarasov KV, Gerzanich V. Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications. Lancet Neurol. 2007;6:258-268. doi: 10.1016/S1474-4422(07)70055-8.
7. Yan Y, Dempsey RJ, Flemmer A, Forbush B, Sun D. Inhibition of Na(+)-K(+)-Cl(-) cotransporter during focal cerebral ischemia decreases edema and neuronal damage. Brain Res. 2003;961:22-31.
8. Chen H, Luo J, Kintner DB, Shull GE, Sun D. Na(+)-dependent chloride transporter (NKCC1)-null mice exhibit less gray and white matter damage after focal cerebral ischemia. J Cereb Blood Flow Metab. 2005;25:54-66. doi: 10.1038/sj.jcbfm.9600006.
9. Huang CL, Cha SK, Wang HR, Xie J, Cobb MH. WNKs: protein kinases with a unique kinase domain. Exp Mol Med. 2007;39:565-573. doi:10.1038/emm.2007.62.
10. Kahle KT, Ring AM, Lifton RP. Molecular physiology of the WNK kinases. Annu Rev Physiol. 2008;70:329-355. doi: 10.1146/annurev. physiol.70.113006.100651.
11. Gagnon KB, Delpire E. Molecular physiology of SPAK and OSR1: two Ste20-related protein kinases regulating ion transport. Physiol Rev. 2012;92:1577-1617. doi: 10.1152/physrev.00009.2012.
12. Alessi DR, Zhang J, Khanna A, Hochdörfer T, Shang Y, Kahle KT. The WNK-SPAK/OSR1 pathway: master regulator of cation-chloride cotransporters. Sci Signal. 2014;7-3. doi: 10.1126/scisignal.2005365.
13. Piala AT, Moon TM, Akella R, He H, Cobb MH, Goldsmith EJ. Chloride sensing by WNK1 involves inhibition of autophosphorylation. Sci Signal. 2014;7:ra41. doi: 10.1126/scisignal.2005050.
14. D eaton SL, Sengupta S, Cobb MH. WNK kinases and blood pressure control. Curr Hypertens Rep. 2009;11:421-426.
15. Kahle KT, Rinehart J, Giebisch G, Gamba G, Hebert SC, Lifton RP. A novel protein kinase signaling pathway essential for blood pressure regulation in humans. Trends Endocrinol Metab. 2008;19:91-95. doi:10.1016/j.tem.2008.01.001.
16. Pacheco-Alvarez D, Gamba G. WNK3 is a putative chloride-sensing kinase. Cell Physiol Biochem. 2011;28:1123-1134. doi: 10.1159/000335848.
17. Kahle KT, Rinehart J, de Los Heros P, Louvi A, Meade P, Vazquez N, et al. WNK3 modulates transport of Cl-in and out of cells: implications for control of cell volume and neuronal excitability. Proc Natl Acad Sci USA. 2005;102:16783-16788. doi: 10.1073/pnas.0508307102.
18. Holden S, Cox J, Raymond FL. Cloning, genomic organization, alternative splicing and expression analysis of the human gene WNK3 (PRKWNK3). Gene. 2004;335:109-119. doi: 10.1016/j. gene.2004.03.009.
19. Haas BR, Cuddapah VA, Watkins S, Rohn KJ, Dy TE, Sontheimer H. With-No-Lysine Kinase 3 (WNK3) stimulates glioma invasion by regulating cell volume. Am J Physiol Cell Physiol. 2011;301:C1150-C1160. doi: 10.1152/ajpcell.00203.2011.
20. Thastrup JO, Rafiqi FH, Vitari AC, Pozo-Guisado E, Deak M, Mehellou Y, et al. SPAK/OSR1 regulate NKCC1 and WNK activity: analysis of WNK isoform interactions and activation by T-loop trans-autophosphorylation. Biochem J. 2012;441:325-337. doi: 10.1042/BJ20111879.
21. de Los Heros P, Kahle KT, Rinehart J, Bobadilla NA, Vázquez N, San Cristobal P, et al. WNK3 bypasses the tonicity requirement for K-Cl cotransporter activation via a phosphatase-dependent pathway. Proc Natl Acad Sci USA. 2006;103:1976-1981. doi: 10.1073/pnas.0510947103.
22. Vitari AC, Thastrup J, Rafiqi FH, Deak M, Morrice NA, Karlsson HK, et al. Functional interactions of the SPAK/OSR1 kinases with their upstream activator WNK1 and downstream substrate NKCC1. Biochem J. 2006;397:223-231. doi: 10.1042/BJ20060220.
23. Oi K, Sohara E, Rai T, Misawa M, Chiga M, Alessi DR, et al. A minor role of WNK3 in regulating phosphorylation of renal NKCC2 and NCC co-transporters in vivo. Biol Open. 2012;1:120-127. doi: 10.1242/bio.2011048.
24. Mederle K, Mutig K, Paliege A, Carota I, Bachmann S, Castrop H, et al. Loss of WNK3 is compensated for by the WNK1/SPAK axis in the kidney of the mouse. Am J Physiol Renal Physiol. 2013;304:F1198-F1209. doi: 10.1152/ajprenal.00288.2012.
25. Flagella M, Clarke LL, Miller ML, Erway LC, Giannella RA, Andringa A, et al. Mice lacking the basolateral Na-K-2Cl cotransporter have impaired epithelial chloride secretion and are profoundly deaf. J Biol Chem. 1999;274:26946-26955.
26. Luo J, Wang Y, Chen H, Kintner DB, Cramer SW, Gerdts JK, et al. A concerted role of Na+-K+-Cl-cotransporter and Na+/Ca2+ exchanger in ischemic damage. J Cereb Blood Flow Metab. 2008;28:737-746. doi:10.1038/sj.jcbfm.9600561.
27. Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD. Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke. 1996;27:1616-1622; discussion 1623.
28. Swanson RA, Morton MT, Tsao-Wu G, Savalos RA, Davidson C, Sharp FR. A semiautomated method for measuring brain infarct volume. J Cereb Blood Flow Metab. 1990;10:290-293. doi: 10.1038/jcbfm.1990.47.
29. Pedraza CE, Monk R, Lei J, Hao Q, Macklin WB. Production, characterization, and efficient transfection of highly pure oligodendrocyte precursor cultures from mouse embryonic neural progenitors. Glia. 2008;56:1339-1352. doi: 10.1002/glia.20702.
30. Beck J, Lenart B, Kintner DB, Sun D. Na-K-Cl cotransporter contributes to glutamate-mediated excitotoxicity. J Neurosci. 2003;23:5061-5068.
31. Shi Y, Chanana V, Watters JJ, Ferrazzano P, Sun D. Role of sodium/hydrogen exchanger isoform 1 in microglial activation and proinflammatory responses in ischemic brains. J Neurochem. 2011;119:124-135. doi:10.1111/j.1471-4159.2011.07403.x.
32. Zhou J, Zhuang J, Li J, Ooi E, Bloom J, Poon C, et al. Long-term poststroke changes include myelin loss, specific deficits in sensory and motor behaviors and complex cognitive impairment detected using active place avoidance. PLoS One. 2013;8:e57503. doi: 10.1371/journal. pone.0057503.
33. Krueger M, Härtig W, Reichenbach A, Bechmann I, Michalski D. Blood-brain barrier breakdown after embolic stroke in rats occurs without ultrastructural evidence for disrupting tight junctions. PLoS One. 2013;8:e56419. doi: 10.1371/journal.pone.0056419.
34. Chen H, Kintner DB, Jones M, Matsuda T, Baba A, Kiedrowski L, et al. AMPA-mediated excitotoxicity in oligodendrocytes: role for Na(+)-K(+)-Cl(-) co-transport and reversal of Na(+)/Ca(2+) exchanger. J Neurochem. 2007;102:1783-1795. doi: 10.1111/j.1471-4159.2007.04638.x.
35. Moriguchi T, Urushiyama S, Hisamoto N, Iemura S, Uchida S, Natsume T, et al. WNK1 regulates phosphorylation of cation-chloride-coupled cotransporters via the STE20-related kinases, SPAK and OSR1. J Biol Chem. 2005;280:42685-42693. doi: 10.1074/jbc.M510042200.
36. Ohta A, Rai T, Yui N, Chiga M, Yang SS, Lin SH, et al. Targeted disruption of the Wnk4 gene decreases phosphorylation of Na-Cl cotransporter, increases Na excretion and lowers blood pressure. Hum Mol Genet. 2009;18:3978-3986. doi: 10.1093/hmg/ddp344.
37. D arman RB, Forbush B. A regulatory locus of phosphorylation in the N terminus of the Na-K-Cl cotransporter, NKCC1. J Biol Chem. 2002;277:37542-37550. doi: 10.1074/jbc.M206293200.
38. McIver SR, Muccigrosso M, Gonzales ER, Lee JM, Roberts MS, Sands MS, et al. Oligodendrocyte degeneration and recovery after focal cerebral ischemia. Neuroscience. 2010;169:1364-1375. doi: 10.1016/j. neuroscience.2010.04.070.
39. Matute C, Domercq M, Pérez-Samartín A, Ransom BR. Protecting white matter from stroke injury. Stroke. 2013;44:1204-1211. doi: 10.1161/STROKEAHA.112.658328.
40. Lee HH, Jurd R, Moss SJ. Tyrosine phosphorylation regulates the membrane trafficking of the potassium chloride co-transporter KCC2. Mol Cell Neurosci. 2010;45:173-179. doi: 10.1016/j.mcn.2010.06.008.
41. Hossain Khan MZ, Sohara E, Ohta A, Chiga M, Inoue Y, Isobe K, et al. Phosphorylation of Na-Cl cotransporter by OSR1 and SPAK kinases regulates its ubiquitination. Biochem Biophys Res Commun. 2012;425:456-461. doi: 10.1016/j.bbrc.2012.07.124.
42. O'Donnell ME, Lam TI, Tran L, Anderson SE. The role of the bloodbrain barrier Na-K-2Cl cotransporter in stroke. Adv Exp Med Biol. 2004;559:67-75.
43. Chen X, Kintner DB, Baba A, Matsuda T, Shull GE, Sun D. Protein aggregation in neurons following OGD: a role for Na+ and Ca2+ ionic dysregulation. J Neurochem. 2010;112:173-182. doi:10.1111/j.1471-4159.2009.06438.x.
44. Chen X, Kintner DB, Luo J, Baba A, Matsuda T, Sun D. Endoplasmic reticulum Ca2+ dysregulation and endoplasmic reticulum stress following in vitro neuronal ischemia: role of Na+-K+-Cl-cotransporter. J Neurochem. 2008;106:1563-1576. doi: 10.1111/j.1471-4159.2008.05501.x.
45. D mytrenko L, Cicanic M, Anderova M, Vorisek I, Ottersen OP, Sykova E, et al. The impact of alpha-syntrophin deletion on the changes in tissue structure and extracellular diffusion associated with cell swelling under physiological and pathological conditions. PLoS One. 2013;8:e68044. doi: 10.1371/journal.pone.0068044.
46. Matsuoka Y, Hossmann KA. Cortical impedance and extracellular volume changes following middle cerebral artery occlusion in cats. J Cereb Blood Flow Metab. 1982;2:466-474. doi: 10.1038/jcbfm.1982.53.
47. Hansen AJ, Zeuthen T. Extracellular ion concentrations during spreading depression and ischemia in the rat brain cortex. Acta Physiol Scand. 1981;113:437-445. doi: 10.1111/j.1748-1716.1981.tb06920.x.
48. Yan Y, Merlin D. Ste20-related proline/alanine-rich kinase: a novel regulator of intestinal inflammation. World J Gastroenterol. 2008;14:6115-6121.
49. Jayakumar AR, Liu M, Moriyama M, Ramakrishnan R, Forbush B 3rd, Reddy PV, et al. Na-K-Cl Cotransporter-1 in the mechanism of ammonia-induced astrocyte swelling. J Biol Chem. 2008;283:33874-33882. doi: 10.1074/jbc.M804016200.
50. Schomberg SL, Su G, Haworth RA, Sun D. Stimulation of Na-K-2Cl cotransporter in neurons by activation of Non-NMDA ionotropic receptor and group-I mGluRs. J Neurophysiol. 2001;85:2563-2575.
51. Sun D, Murali SG. Stimulation of Na+-K+-2Cl-cotransporter in neuronal cells by excitatory neurotransmitter glutamate. Am J Physiol. 1998;275(3 Pt 1):C772-C779.
52. Gagnon KB, Delpire E. Physiology of SLC12 transporters: lessons from inherited human genetic mutations and genetically engineered mouse knockouts. Am J Physiol Cell Physiol. 2013;304:C693-C714. doi:10.1152/ajpcell.00350.2012.
53. Sengupta S, Tu SW, Wedin K, Earnest S, Stippec S, Luby-Phelps K, et al. Interactions with WNK (with no lysine) family members regulate oxidative stress response 1 and ion co-transporter activity. J Biol Chem. 2012;287:37868-37879. doi: 10.1074/jbc.M112.398750.
54. Lee AY, Chen W, Stippec S, Self J, Yang F, Ding X, et al. Protein kinase WNK3 regulates the neuronal splicing factor Fox-1. Proc Natl Acad Sci USA. 2012;109:16841-16846. doi: 10.1073/pnas.1215406109.