Orginal Article

Role of Mitogen-activated Protein Kinase Pathways in Expression of Aquaporin-4 in Astrocytes after Oxygen-glucose Deprivation in Rats

  • QIAN Chao ,
  • LIU Feng ,
  • XIAO Xue-qian ,
  • LI Feng ,
  • GAO Xi-song ,
  • DANG Lian-feng ,
  • ZHANG Yu
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  • Deparment of Neurosurgery, No. 215 Hospital of Shaanxi Nuclear Industry, Xianyang, Shaanxi 712000, China

Received date: 2017-04-02

  Revised date: 2017-06-08

  Online published: 2017-12-28

Abstract

Objective To investigate whether mitogen-activated protein kinases (MAPKs), which were involved in changes in osmolality, might mediate aquaporin-4 (AQP4) expression in astrocytes after oxygen-glucose deprivation (OGD) in rats. Methods Astrocytes were obtained from new born Sprague-Dawley rats. The P2 cells were divided into control group, OGD group and inhibitors of U0126, SB203580 and SP600125 groups. The latter groups underwent OGD for five hours and reoxygenated, the inhibitors of U0126, SB203580 and SP600125 (1 μmol/L and 10 μmol/L, respectively) groups, named U1, U10, SB1, SB10, SP1 and SP10 groups, respectively, were cultured with the inhibitors for twelve hours. The volume of cells in OGD group was measured half, one, one and half, two, three, four, eight and twelve hours after reoxygenation, and the expression of AQP4 was detected half, one, one and half, eight and twelve hours after reoxygenation with Western blotting. The expression of AQP4, and phosphorylation of extracellular regulated protein kinases (p-ERK), c-Jun N-terminal kinase (p-JNK) and p38 MAPK (p-p38 MAPK) was detected 24 hours after reoxygenation in all the groups, while the activity of lactate dehydrogenase (LDH) was measured. Results The volume of cells increased in OGD group one and half, two, three and four hours after reoxygenation compared with those in the control group (P<0.001), and the expression of AQP4 also increased in OGD group after reoxygenation (P<0.001), especially 1.5 hours of reoxygenation. The expression of AQP4, p-ERK, p-JNK and p-p38 MAPK increased in OGD group after five hours of OGD compared with those in the control group (P<0.001), and the expression of p-ERK, p-JNK and p-p38 MAPK decreased in the inhibitors groups compared with those in OGD group (P<0.001), and the expression of AQP4 decreased in SB10 group (P<0.001). The activity of LDH was less in all the inhibitors groups except SP1 and SB1 groups than in OGD group (P<0.01), and was the least in SB10 group (P<0.001). Conclusion MAPKs signal pathway, especially p38 MAPK, may promote AQP4 expression in astrocytes after OGD in rat, and play a role in cells death.

Cite this article

QIAN Chao , LIU Feng , XIAO Xue-qian , LI Feng , GAO Xi-song , DANG Lian-feng , ZHANG Yu . Role of Mitogen-activated Protein Kinase Pathways in Expression of Aquaporin-4 in Astrocytes after Oxygen-glucose Deprivation in Rats[J]. Chinese Journal of Rehabilitation Theory and Practice, 2017 , 23(12) : 1397 -1402 . DOI: 10.3969/j.issn.1006-9771.2017.12.006

References

[1] Hubbard JA, Szu JI, Binder DK. The role of aquaporin-4 in synaptic plasticity, memory and disease [J]. Brain Res Bull, 2017, 6(17): 30115-30116.
[2] Aghayev K, Bal E, Rahimli T, et al. Aquaporin-4 expression is not elevated in mild hydrocephalus [J]. Acta Neurochir, 2012, 154(4): 753-759.
[3] Ximenes SA. Metal ion toxins and brain aquaporin-4 expression: an overview [J]. Front Neurosci, 2016, 1(10): 233-238.
[4] Filippidis AS, Carozza RB, Rekate HL. Aquaporins in brain edema and neuropathological conditions [J]. Int J Mol Sci, 2016, 18(1): E55.
[5] Yang J, Zhang R, Shi C, et al. AQP4 association with amyloid deposition and astrocyte pathology in the Tg-ArcSwe mouse model of Alzheimer's disease [J]. Alzheimers Dis, 2017, 57(1): 157-169.
[6] Raghupathi R. Cell death mechanisms following traumatic brain injury [J]. Brain Pathol, 2004, 14(2): 215-222.
[7] Nito C, Kamada H, Endo H, et al. Involvement of mitogen-activated protein kinase pathways in expression of the water channel protein aquaporin-4 after ischemia in rat cortical astrocytes [J]. J Neurotrauma, 2012, 29(14): 2404-2412.
[8] Xiong LL, Tan Y, Ma HY, et al. Administration of SB239063, a potent p38 MAPK inhibitor, alleviates acute lung injury induced by intestinal ischemia reperfusion in rats associated with AQP4 down regulation [J]. Int Immunopharmacol, 2016, 38(3): 54-60.
[9] Jayakumar AR, Rao KV, Panickar KS, et al. Trauma-induced cell swelling in cultured astrocytes [J]. Neuropathol Exp Neurol, 2008, 67(5): 417-427.
[10] Yu J, Jiang Z, Ning L, et al. Protective HSP70 induction by Z-ligustilide against oxygen-glucose deprivation injury via activation of the MAPK pathway but not of HSF1 [J]. Biol Pharm Bull, 2015, 38(10): 1564-1572.
[11] Chen YQ, Gao F, Jiang R, et al. Down-regulation of AQP4 expression via p38 MAPK signaling in temozolomide-induced glioma cells growth inhibition and invasion impairment [J]. Cell Biochem, 2017, 118(12): 4905-4913.
[12] Nito C, Kamada H, Endo H, et al. Role of the p38 mitogen-activated protein kinase/cytosolic phospholipase A(2) signaling pathway in blood-brain barrier disruption after focal cerebral ischemia and reperfusion [J]. Cereb Blood Flow Metab, 2008, 28(10): 1686-1696.
[13] Qi LL, Fang SH, Shi WZ, et al. CysLT2 receptor-mediated AQP4 up-regulation is involved in ischemic-like injury through activation of ERK and p38 MAPK in rat astrocytes [J]. Life Sci, 2011, 88(3): 50-60.
[14] De Bellis M, Pisani F, Mola MG, et al. Translational read through generates new astrocyte AQP4 isoforms that modulate supramolecular clustering, glial endfeet localization, and water transport [J]. Glia, 2017, 65(5): 790-803.
[15] Yang X, Ransom BR, Ma JF, et al. The role of AQP4 in neuromyelitis optica: more answers, more questions [J]. J Neuroimmunol, 2016, 298(15): 63-70.
[16] Ikeshima KH. Neuroimmunological implications of AQP4 in astrocytes [J]. Int J Mol Sci, 2016, 17(8): 1306-1322.
[17] Hinson SR, Lennon VA, Pittock SJ. Autoimmune AQP4 channelopathies and neuromyelitis optica spectrum disorders [J]. Handb Clin Neurol, 2016, 133: 377-403
[18] Li S, Hu X, Zhang M, et al. Remote ischemic post-conditioning improves neurological function by AQP4 down-regulation in astrocytes [J]. Behav Brain Res, 2015, 289(1): 1-8.
[19] Assentoft M, Larsen BR, MacAulay N. Regulation and function of AQP4 in the central nervous system [J]. Neurochem Res, 2015, 40(12): 2615-2627.
[20] Frydenlund DS, Bhardwaj A, Otsuka T, et al. Temporary loss of perivascular aquaporin-4 in neocortex after transient middle cerebral artery occlusion in mice [J]. Proc Natl Acad Sci USA, 2006, 103(36): 13532-13536.
[21] Piao CS, Kim JB, Han PL, et al. Administration of the p38 MAPK inhibitor SB203580 affords brain protection with a wide therapeutic window against focal ischemic insult [J]. Neurosci Res, 2003, 73(4): 537-544.
[22] Tait MJ, Saadoun S, Bell BA, et al. Increased brain edema in AQP4-null mice in an experimental model of subarachnoid hemorrhage [J]. Neuroscience, 2010, 167(1): 60-67.
[23] Manley GT, Fujimura M, Ma T, et al. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke [J]. Nat Med, 2000, 6(2): 159-163.
[24] Arima H, Yamamoto N, Sobue K, et al. Hyperosmolar mannitol stimulates expression of aquaporins 4 and 9 through a p38 mitogen-activated protein kinase-dependent pathway in rat astrocytes [J]. Biol Chem, 2003, 278(45): 44525-44534.
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