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Translational Stroke Research

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01.07.2012 | Review Article

Excitatory and Mitogenic Signaling in Cell Death, Blood–brain Barrier Breakdown, and BBB Repair after Intracerebral Hemorrhage

verfasst von: Da-Zhi Liu, Frank R. Sharp

Erschienen in: Translational Stroke Research | Sonderheft 1/2012

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Abstract

Intracerebral hemorrhage (ICH) results in the release of a large number of endogenous molecules, including glutamate, Ca²⁺, ROS, thrombin, heme, iron, TNF-α, and others. These molecules participate in excitatory and mitogenic signaling transduction in which N-methyl-d-aspartate (NMDA) receptors and Src family kinases (SFKs) are implicated. Mitogenic signaling initiates the cell cycle for normal cell division of microglia and neural progenitor cells, whereas aberrant mitogenic signaling causes toxicity, killing neurons, astrocytes, and brain microvascular endothelial cells in neurological diseases including ICH. In this review, we summarize (1) how SFKs modulate NMDA receptors to kill neurons following ICH and (2) how SFKs modulate mitogenic signaling transduction to kill neurons and play a role in disrupting the blood–brain barrier (BBB) immediately following ICH and in repairing the BBB during the recovery phases weeks following ICH.

Thiex R, Tsirka SE. Brain edema after intracerebral hemorrhage: mechanisms, treatment options, management strategies, and operative indications. Neurosurg Focus. 2007;22(5):E6.PubMedCrossRef

Thiex R, Weis J, Krings T, Barreiro S, Yakisikli-Alemi F, Gilsbach JM, et al. Addition of intravenous N-methyl-D-aspartate receptor antagonists to local fibrinolytic therapy for the optimal treatment of experimental intracerebral hemorrhages. J Neurosurg. 2007;106(2):314–20.PubMedCrossRef

Hossain MI, Kamaruddin MA, Cheng HC. Aberrant regulation and function of Src-family tyrosine kinases—their potential contributions to glutamate-induced neurotoxicity. Clin Exp Pharmacol Physiol. 2012. doi:10.1111/j.1440-1681.2011.05621.x.

Liu DZ, Cheng XY, Ander BP, Xu H, Davis RR, Gregg JP, et al. Src kinase inhibition decreases thrombin-induced injury and cell cycle re-entry in striatal neurons. Neurobiol Dis. 2008;30(2):201–11.PubMedCrossRef

Liu DZ, Ander BP, Sharp FR. Cell cycle inhibition without disruption of neurogenesis is a strategy for treatment of central nervous system diseases. Neurobiol Dis. 2010;37:549–57.PubMedCrossRef

Liu DZ, Ander BP. Cell cycle inhibition without disruption of neurogenesis is a strategy for treatment of aberrant cell cycle diseases: an update. Sci World J, 2012, (in press).

Liu DZ, Ander BP. Cell cycle phase transitions: signposts for aberrant cell cycle reentry in dying mature neurons. J Cytol Histol. 2011;2:5.

Ardizzone TD, Lu A, Wagner KR, Tang Y, Ran R, Sharp FR. Glutamate receptor blockade attenuates glucose hypermetabolism in perihematomal brain after experimental intracerebral hemorrhage in rat. Stroke. 2004;35(11):2587–91.PubMedCrossRef

Groveman BR, Feng S, Fang XQ, Pflueger M, Lin SX, Bienkiewicz EA, et al. The regulation of N-methyl-D-aspartate receptors by Src kinase. FEBS J. 2012;279(1):20–8.PubMedCrossRef

10.

Ardizzone TD, Zhan X, Ander BP, Sharp FR. SRC kinase inhibition improves acute outcomes after experimental intracerebral hemorrhage. Stroke. 2007;38(5):1621–5.PubMedCrossRef

11.

Sharp F, Liu DZ, Zhan X, Ander BP. Intracerebral hemorrhage injury mechanisms: glutamate neurotoxicity, thrombin, and Src. Acta Neurochir Suppl. 2008;105:43–6.PubMedCrossRef

12.

Oda H, Kumar S, Howley PM. Regulation of the Src family tyrosine kinase Blk through E6AP-mediated ubiquitination. Proc Natl Acad Sci USA. 1999;96(17):9557–62.PubMedCrossRef

13.

Biscardi JS, Ishizawar RC, Silva CM, Parsons SJ. Tyrosine kinase signalling in breast cancer: epidermal growth factor receptor and c-Src interactions in breast cancer. Breast Cancer Res. 2000;2(3):203–10.PubMedCrossRef

14.

Grimmler M, Wang Y, Mund T, Cilensek Z, Keidel EM, Waddell MB, et al. Cdk-inhibitory activity and stability of p27Kip1 are directly regulated by oncogenic tyrosine kinases. Cell. 2007;128(2):269–80.PubMedCrossRef

15.

Kasahara K, Nakayama Y, Nakazato Y, Ikeda K, Kuga T, Yamaguchi N. Src signaling regulates completion of abscission in cytokinesis through ERK/MAPK activation at the midbody. J Biol Chem. 2007;282(8):5327–39.PubMedCrossRef

16.

Liu Z, Falola J, Zhu X, Gu Y, Kim LT, Sarosi GA, et al. Antiproliferative effects of Src inhibition on medullary thyroid cancer. J Clin Endocrinol Metab. 2004;89(7):3503–9.PubMedCrossRef

17.

Mishra R, Wang Y, Simonson MS. Cell cycle signaling by endothelin-1 requires Src nonreceptor protein tyrosine kinase. Mol Pharmacol. 2005;67(6):2049–56.PubMedCrossRef

18.

Taylor SJ, Shalloway D. The cell cycle and c-Src. Curr Opin Genet Dev. 1993;3(1):26–34.PubMedCrossRef

19.

Liu DZ, Ander BP, Xu H, Shen Y, Kaur P, Deng W, et al. Blood–brain barrier breakdown and repair by Src after thrombin-induced injury. Ann Neurol. 2010;67(4):526–33.PubMedCrossRef

20.

Liu DZ, Sharp FR. The dual role of SRC kinases in intracerebral hemorrhage. Acta Neurochir Suppl. 2011;111:77–81.PubMedCrossRef

21.

Copani A, Condorelli F, Caruso A, Vancheri C, Sala A, Giuffrida Stella AM, et al. Mitotic signaling by beta-amyloid causes neuronal death. FASEB J. 1999;13(15):2225–34.PubMed

22.

Varvel NH, Bhaskar K, Patil AR, Pimplikar SW, Herrup K, Lamb BT. Abeta oligomers induce neuronal cell cycle events in Alzheimer's disease. J Neurosci. 2008;28(43):10786–93.PubMedCrossRef

23.

Williamson R, Scales T, Clark BR, Gibb G, Reynolds CH, Kellie S, et al. Rapid tyrosine phosphorylation of neuronal proteins including tau and focal adhesion kinase in response to amyloid-beta peptide exposure: involvement of Src family protein kinases. J Neurosci. 2002;22(1):10–20.PubMed

24.

Wang H, Reiser G. Thrombin signaling in the brain: the role of protease-activated receptors. Biol Chem. 2003;384(2):193–202.PubMedCrossRef

25.

Ohnishi M, Katsuki H, Fujimoto S, Takagi M, Kume T, Akaike A. Involvement of thrombin and mitogen-activated protein kinase pathways in hemorrhagic brain injury. Exp Neurol. 2007;206(1):43–52.PubMedCrossRef

26.

Guan J, Luo Y, Denker BM. Purkinje cell protein-2 (Pcp2) stimulates differentiation in PC12 cells by Gbetagamma-mediated activation of Ras and p38 MAPK. Biochem J. 2005;392(Pt 2):389–97.PubMed

27.

Segarra J, Balenci L, Drenth T, Maina F, Lamballe F. Combined signaling through ERK, PI3K/AKT, and RAC1/p38 is required for met-triggered cortical neuron migration. J Biol Chem. 2006;281(8):4771–8.PubMedCrossRef

28.

Lopez-Bergami P, Ronai Z. Requirements for PKC-augmented JNK activation by MKK4/7. Int J Biochem Cell Biol. 2008;40(5):1055–64.PubMedCrossRef

29.

Dwivedi Y, Pandey GN. Effects of treatment with haloperidol, chlorpromazine, and clozapine on protein kinase C (PKC) and phosphoinositide-specific phospholipase C (PI-PLC) activity and on mRNA and protein expression of PKC and PLC isozymes in rat brain. J Pharmacol Exp Ther. 1999;291(2):688–704.PubMed

30.

Zhu X, Rottkamp CA, Boux H, Takeda A, Perry G, Smith MA. Activation of p38 kinase links tau phosphorylation, oxidative stress, and cell cycle-related events in Alzheimer disease. J Neuropathol Exp Neurol. 2000;59(10):880–8.PubMed

31.

Khurana V, Lu Y, Steinhilb ML, Oldham S, Shulman JM, Feany MB. TOR-mediated cell-cycle activation causes neurodegeneration in a Drosophila tauopathy model. Curr Biol. 2006;16(3):230–41.PubMedCrossRef

32.

Xing B, Xin T, Hunter RL, Bing G. Pioglitazone inhibition of lipopolysaccharide-induced nitric oxide synthase is associated with altered activity of p38 MAP kinase and PI3K/Akt. J Neuroinflammation. 2008;5:4.PubMedCrossRef

33.

Goody RJ, Beckham JD, Rubtsova K, Tyler KL. JAK-STAT signaling pathways are activated in the brain following reovirus infection. J Neurovirol. 2007;13(4):373–83.PubMedCrossRef

34.

Li N, Wang C, Wu Y, Liu X, Cao X. Ca2+/calmodulin-dependent protein kinase II promotes cell cycle progression by directly activating MEK1 and subsequently modulating p27 phosphorylation. J Biol Chem. 2009;284(5):3021–7.PubMedCrossRef

35.

Mao LM, Tang QS, Wang JQ. Regulation of extracellular signal-regulated kinase phosphorylation in cultured rat striatal neurons. Brain Res Bull. 2009;78(6):328–34.PubMedCrossRef

36.

de Bernardo S, Canals S, Casarejos MJ, Solano RM, Menendez J, Mena MA. Role of extracellular signal-regulated protein kinase in neuronal cell death induced by glutathione depletion in neuron/glia mesencephalic cultures. J Neurochem. 2004;91(3):667–82.PubMedCrossRef

37.

Copani A, Nicoletti F. Cell-cycle mechanisms and neuronal cell death. New York: Kluwer Academic; 2005.CrossRef

38.

Qian JY, Leung A, Harding P, LaPointe MC. PGE2 stimulates human brain natriuretic peptide expression via EP4 and p42/44 MAPK. Am J Physiol Heart Circ Physiol. 2006;290(5):H1740–6.PubMedCrossRef

39.

Fiebich BL, Schleicher S, Spleiss O, Czygan M, Hull M. Mechanisms of prostaglandin E2-induced interleukin-6 release in astrocytes: possible involvement of EP4-like receptors, p38 mitogen-activated protein kinase and protein kinase C. J Neurochem. 2001;79(5):950–8.PubMedCrossRef

40.

Meissirel C, Ruiz de Almodovar C, Knevels E, Coulon C, Chounlamountri N, Segura I, et al. VEGF modulates NMDA receptors activity in cerebellar granule cells through Src-family kinases before synapse formation. Proc Natl Acad Sci USA. 2011;108(33):13782–7.PubMedCrossRef

41.

Rosenberg GA. Matrix metalloproteinases and their multiple roles in neurodegenerative diseases. Lancet Neurol. 2009;8(2):205–16.PubMedCrossRef

42.

Xiao L, Hu C, Feng C, Chen Y. Switching of N-methyl-D-aspartate (NMDA) receptor-favorite intracellular signal pathways from ERK1/2 protein to p38 mitogen-activated protein kinase leads to developmental changes in NMDA neurotoxicity. J Biol Chem. 2011;286(23):20175–93.PubMedCrossRef

43.

Centeno C, Repici M, Chatton JY, Riederer BM, Bonny C, Nicod P, et al. Role of the JNK pathway in NMDA-mediated excitotoxicity of cortical neurons. Cell Death Differ. 2007;14(2):240–53.PubMedCrossRef

44.

Jantas D, Szymanska M, Budziszewska B, Lason W. An involvement of BDNF and PI3-K/Akt in the anti-apoptotic effect of memantine on staurosporine-evoked cell death in primary cortical neurons. Apoptosis. 2009;14(7):900–12.PubMedCrossRef

45.

Yu XM, Askalan R, Keil 2nd GJ, Salter MW. NMDA channel regulation by channel-associated protein tyrosine kinase Src. Science. 1997;275(5300):674–8.PubMedCrossRef

46.

Salter MW, Kalia LV. Src kinases: a hub for NMDA receptor regulation. Nat Rev Neurosci. 2004;5(4):317–28.PubMedCrossRef

47.

Trepanier CH, Jackson MF, MacDonald JF. Regulation of NMDA receptors by the tyrosine kinase Fyn. FEBS J. 2012;279(1):12–9.PubMedCrossRef

48.

Choi UB, Xiao S, Wollmuth LP, Bowen ME. Effect of Src kinase phosphorylation on disordered C-terminal domain of N-methyl-D-aspartic acid (NMDA) receptor subunit GluN2B protein. J Biol Chem. 2011;286(34):29904–12.PubMedCrossRef

49.

Heidinger V, Manzerra P, Wang XQ, Strasser U, Yu SP, Choi DW, et al. Metabotropic glutamate receptor 1-induced upregulation of NMDA receptor current: mediation through the Pyk2/Src-family kinase pathway in cortical neurons. J Neurosci. 2002;22(13):5452–61.PubMed

50.

Bernabeu R, Sharp FR. NMDA and AMPA/kainate glutamate receptors modulate dentate neurogenesis and CA3 synapsin-I in normal and ischemic hippocampus. J Cereb Blood Flow Metab. 2000;20(12):1669–80.PubMedCrossRef

51.

Liu J, Solway K, Messing RO, Sharp FR. Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J Neurosci. 1998;18(19):7768–78.PubMed

52.

Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD. Blood–brain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol. 2006;1(3):223–36.PubMedCrossRef

53.

Banerjee S, Bhat MA. Neuron-glial interactions in blood–brain barrier formation. Annu Rev Neurosci. 2007;30:235–58.PubMedCrossRef

54.

Ohab JJ, Fleming S, Blesch A, Carmichael ST. A neurovascular niche for neurogenesis after stroke. J Neurosci. 2006;26(50):13007–16.PubMedCrossRef

55.

Palmer TD, Willhoite AR, Gage FH. Vascular niche for adult hippocampal neurogenesis. J Comp Neurol. 2000;425(4):479–94.PubMedCrossRef

Titel: Excitatory and Mitogenic Signaling in Cell Death, Blood–brain Barrier Breakdown, and BBB Repair after Intracerebral Hemorrhage
verfasst von: Da-Zhi Liu
Frank R. Sharp
Publikationsdatum: 01.07.2012
Verlag: Springer-Verlag
Erschienen in: Translational Stroke Research / Ausgabe Sonderheft 1/2012
Print ISSN: 1868-4483
Elektronische ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-012-0147-z

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