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The Expression Changes of Myelin and Lymphocyte Protein (MAL) Following Optic Nerve Crush in Adult Rats Retinal Ganglion Cells

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Abstract

Myelin and lymphocyte protein (MAL), a component of compact myelin, is highly expressed in oligodendrocytes and Schwann cells. It has been reported that MAL may play a vital role in the process of neuronal apoptosis following acute spinal cord injury. However, acquaintance regarding its distribution and possible function in the retina is limited. Therefore, in a rodent model of optic nerve crush (ONC), the dynamic changes of MAL in retina was detected. The expression of MAL was mainly located in the retinal ganglion cells (RGCs) and was increased strongly after ONC. The peak of MAL expression appeared on the third day. In addition, there was a concomitant upregulation of active-caspase-3, which also co-localized with MAL in RGCs. Moreover, co-localization of MAL with terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling (TUNEL) was detected in RGCs after ONC. Collectively, all these results suggested that the upregulation of MAL might play an important role in the pathophysiology of RGCs after ONC.

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References

  • Allcutt D, Berry M, Sievers J (1984) A qualitative comparison of the reactions of retinal ganglion cell axons to optic nerve crush in neonatal and adult mice. Brain Res 318:231–240

    Article  CAS  PubMed  Google Scholar 

  • Alonso MA, Millan J (2001) The role of lipid rafts in signalling and membrane trafficking in T lymphocytes. J Cell Sci 114:3957–3965

    CAS  PubMed  Google Scholar 

  • Alonso MA, Weissman SM (1987) cDNA cloning and sequence of MAL, a hydrophobic protein associated with human T-cell differentiation. Proc Natl Acad Sci U S A 84:1997–2001

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Boatright KM, Salvesen GS (2003) Mechanisms of caspase activation. Curr Opin Cell Biol 15:725–731

    Article  CAS  PubMed  Google Scholar 

  • Bouchard VJ, Rouleau M, Poirier GG (2003) PARP-1, a determinant of cell survival in response to DNA damage. Exp Hematol 31:446–454

    Article  CAS  PubMed  Google Scholar 

  • Buffart TE, Overmeer RM, Steenbergen RD, Tijssen M, van Grieken NC, Snijders PJ, Grabsch HI, van de Velde CJ, Carvalho B, Meijer GA (2008) MAL promoter hypermethylation as a novel prognostic marker in gastric cancer. Br J Cancer 99:1802–1807

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cao W, Zhang ZY, Xu Q, Sun Q, Yan M, Zhang J, Zhang P, Han ZG, Chen WT (2010) Epigenetic silencing of MAL, a putative tumor suppressor gene, can contribute to human epithelium cell carcinoma. Mol Cancer 9:296

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Castano A, Bell MD, Perry VH (1996) Unusual aspects of inflammation in the nervous system: Wallerian degeneration. Neurobiol Aging 17:745–751

    Article  CAS  PubMed  Google Scholar 

  • Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, Christ F, Schwab ME (2000) Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 403:434–439

    Article  CAS  PubMed  Google Scholar 

  • Fischer D, Pavlidis M, Thanos S (2000) Cataractogenic lens injury prevents traumatic ganglion cell death and promotes axonal regeneration both in vivo and in culture. Invest Ophthalmol Vis Sci 41:3943–3954

    CAS  PubMed  Google Scholar 

  • Frank M (2000) MAL, a proteolipid in glycosphingolipid enriched domains: functional implications in myelin and beyond. Prog Neurobiol 60:531–544

    Article  CAS  PubMed  Google Scholar 

  • Frank M, van der Haar ME, Schaeren-Wiemers N, Schwab ME (1998) rMAL is a glycosphingolipid-associated protein of myelin and apical membranes of epithelial cells in kidney and stomach. J Neurosci 18:4901–4913

    CAS  PubMed  Google Scholar 

  • Goldenberg-Cohen N, Dratviman-Storobinsky O, El Dadon Bar S, Cheporko Y, Hochhauser E (2011) Protective effect of Bax ablation against cell loss in the retinal ganglion layer induced by optic nerve crush in transgenic mice. J Neuroophthalmol 31:331–338

    Article  PubMed  Google Scholar 

  • GrandPre T, Nakamura F, Vartanian T, Strittmatter SM (2000) Identification of the Nogo inhibitor of axon regeneration as a reticulon protein. Nature 403:439–444

    Article  CAS  PubMed  Google Scholar 

  • Gregory MS, Hackett CG, Abernathy EF, Lee KS, Saff RR, Hohlbaum AM, Moody KS, Hobson MW, Jones A, Kolovou P, Karray S, Giani A, John SW, Chen DF, Marshak-Rothstein A, Ksander BR (2011) Opposing roles for membrane bound and soluble Fas ligand in glaucoma-associated retinal ganglion cell death. PLoS One 6:e17659

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gupta VK, You Y, Li JC, Klistorner A, Graham SL (2013) Protective effects of 7,8-dihydroxyflavone on retinal ganglion and RGC-5 cells against excitotoxic and oxidative stress. J Mol Neurosci 49:96–104

    Article  CAS  PubMed  Google Scholar 

  • Horne HN, Lee PS, Murphy SK, Alonso MA, Olson JA Jr, Marks JR (2009) Inactivation of the MAL gene in breast cancer is a common event that predicts benefit from adjuvant chemotherapy. Mol Cancer Res 7:199–209

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hu Y, Park KK, Yang L, Wei X, Yang Q, Cho KS, Thielen P, Lee AH, Cartoni R, Glimcher LH, Chen DF, He Z (2012) Differential effects of unfolded protein response pathways on axon injury-induced death of retinal ganglion cells. Neuron 73:445–452

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Joachim SC, Mondon C, Gramlich OW, Grus FH, Dick HB (2014) Apoptotic retinal ganglion cell death in an autoimmune glaucoma model is accompanied by antibody depositions. J Mol Neurosci 52:216–224

    Article  CAS  PubMed  Google Scholar 

  • Katai N, Yoshimura N (1999) Apoptotic retinal neuronal death by ischemia-reperfusion is executed by two distinct caspase family proteases. Invest Ophthalmol Vis Sci 40:2697–2705

    CAS  PubMed  Google Scholar 

  • Kermer P, Klocker N, Labes M, Thomsen S, Srinivasan A, Bahr M (1999) Activation of caspase-3 in axotomized rat retinal ganglion cells in vivo. FEBS Lett 453:361–364

    Article  CAS  PubMed  Google Scholar 

  • Kim T, Fiedler K, Madison DL, Krueger WH, Pfeiffer SE (1995) Cloning and characterization of MVP17: a developmentally regulated myelin protein in oligodendrocytes. J Neurosci Res 42:413–422

    Article  CAS  PubMed  Google Scholar 

  • Krupinski J, Ferrer I, Barrachina M, Secades JJ, Mercadal J, Lozano R (2002) CDP-choline reduces pro-caspase and cleaved caspase-3 expression, nuclear DNA fragmentation, and specific PARP-cleaved products of caspase activation following middle cerebral artery occlusion in the rat. Neuropharmacology 42:846–854

    Article  CAS  PubMed  Google Scholar 

  • Kwon KB, Yoo SJ, Ryu DG, Yang JY, Rho HW, Kim JS, Park JW, Kim HR, Park BH (2002) Induction of apoptosis by diallyl disulfide through activation of caspase-3 in human leukemia HL-60 cells. Biochem Pharmacol 63:41–47

    Article  CAS  PubMed  Google Scholar 

  • Leung CK, Lindsey JD, Crowston JG, Lijia C, Chiang S, Weinreb RN (2008) Longitudinal profile of retinal ganglion cell damage after optic nerve crush with blue-light confocal scanning laser ophthalmoscopy. Invest Ophthalmol Vis Sci 49:4898–4902

    Article  PubMed  Google Scholar 

  • Li Y, Schlamp CL, Nickells RW (1999) Experimental induction of retinal ganglion cell death in adult mice. Invest Ophthalmol Vis Sci 40:1004–1008

    CAS  PubMed  Google Scholar 

  • Li A, Zou F, Fu H, Cui G, Yan Y, Wu Q, Gu X (2013) Upregulation of CRM1 relates to neuronal apoptosis after traumatic brain injury in adult rats. J Mol Neurosci 51:208–218

    Article  PubMed  Google Scholar 

  • Mao H, Liu J, Shi W, Huang Q, Xu X, Ni L, Zou F, Shi J, Li D, Liu Y, Chen J (2013) The expression patterns of septin-9 after traumatic brain injury in rat brain. J Mol Neurosci 51:558–566

    Article  CAS  PubMed  Google Scholar 

  • Mimori K, Shiraishi T, Mashino K, Sonoda H, Yamashita K, Yoshinaga K, Masuda T, Utsunomiya T, Alonso MA, Inoue H, Mori M (2003) MAL gene expression in esophageal cancer suppresses motility, invasion and tumorigenicity and enhances apoptosis through the Fas pathway. Oncogene 22:3463–3471

    Article  CAS  PubMed  Google Scholar 

  • Nadal-Nicolas FM, Jimenez-Lopez M, Sobrado-Calvo P, Nieto-Lopez L, Canovas-Martinez I, Salinas-Navarro M, Vidal-Sanz M, Agudo M (2009) Brn3a as a marker of retinal ganglion cells: qualitative and quantitative time course studies in naive and optic nerve-injured retinas. Invest Ophthalmol Vis Sci 50:3860–3868

    Article  PubMed  Google Scholar 

  • Neufeld AH, Liu B (2003) Glaucomatous optic neuropathy: when glia misbehave. Neuroscientist 9:485–495

    Article  CAS  PubMed  Google Scholar 

  • Overmeer RM, Henken FE, Bierkens M, Wilting SM, Timmerman I, Meijer CJ, Snijders PJ, Steenbergen RD (2009) Repression of MAL tumour suppressor activity by promoter methylation during cervical carcinogenesis. J Pathol 219:327–336

    Article  CAS  PubMed  Google Scholar 

  • Parrilla-Reverter G, Agudo M, Sobrado-Calvo P, Salinas-Navarro M, Villegas-Perez MP, Vidal-Sanz M (2009) Effects of different neurotrophic factors on the survival of retinal ganglion cells after a complete intraorbital nerve crush injury: a quantitative in vivo study. Exp Eye Res 89:32–41

    Article  CAS  PubMed  Google Scholar 

  • Quigley HA, McKinnon SJ, Zack DJ, Pease ME, Kerrigan-Baumrind LA, Kerrigan DF, Mitchell RS (2000) Retrograde axonal transport of BDNF in retinal ganglion cells is blocked by acute IOP elevation in rats. Invest Ophthalmol Vis Sci 41:3460–3466

    CAS  PubMed  Google Scholar 

  • Rong X, Yang S, Miao H, Guo T, Wang Z, Shi W, Mo X, Yuan W, Jin T (2012) Effects of erythropoietin-dextran microparticle-based PLGA/PLA microspheres on RGCs. Invest Ophthalmol Vis Sci 53:6025–6034

    Article  CAS  PubMed  Google Scholar 

  • Schaeren-Wiemers N, Schaefer C, Valenzuela DM, Yancopoulos GD, Schwab ME (1995a) Identification of new oligodendrocyte- and myelin-specific genes by a differential screening approach. J Neurochem 65:10–22

    Article  CAS  PubMed  Google Scholar 

  • Schaeren-Wiemers N, Valenzuela DM, Frank M, Schwab ME (1995b) Characterization of a rat gene, rMAL, encoding a protein with four hydrophobic domains in central and peripheral myelin. J Neurosci 15:5753–5764

    CAS  PubMed  Google Scholar 

  • Schaeren-Wiemers N, Bonnet A, Erb M, Erne B, Bartsch U, Kern F, Mantei N, Sherman D, Suter U (2004) The raft-associated protein MAL is required for maintenance of proper axon—glia interactions in the central nervous system. J Cell Biol 166:731–742

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sharifi AM, Eslami H, Larijani B, Davoodi J (2009) Involvement of caspase-8, -9, and -3 in high glucose-induced apoptosis in PC12 cells. Neurosci Lett 459:47–51

    Article  CAS  PubMed  Google Scholar 

  • Shu Q, Xu Y, Zhuang H, Fan J, Sun Z, Zhang M, Xu G (2014) Ras homolog enriched in the brain is linked to retinal ganglion cell apoptosis after light injury in rats. J Mol Neurosci

  • Sucher NJ, Lipton SA, Dreyer EB (1997) Molecular basis of glutamate toxicity in retinal ganglion cells. Vis Res 37:3483–3493

    Article  CAS  PubMed  Google Scholar 

  • Tezel G (2006) Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences. Prog Retin Eye Res 25:490–513

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tsai RK, Chang CH, Sheu MM, Huang ZL (2010) Anti-apoptotic effects of human granulocyte colony-stimulating factor (G-CSF) on retinal ganglion cells after optic nerve crush are PI3K/AKT-dependent. Exp Eye Res 90:537–545

    Article  CAS  PubMed  Google Scholar 

  • van Wijk SJ, Hageman GJ (2005) Poly(ADP-ribose) polymerase-1 mediated caspase-independent cell death after ischemia/reperfusion. Free Radic Biol Med 39:81–90

    PubMed  Google Scholar 

  • Vigneswara V, Berry M, Logan A, Ahmed Z (2012) Pharmacological inhibition of caspase-2 protects axotomised retinal ganglion cells from apoptosis in adult rats. PLoS One 7:e53473

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wilson AM, Morquette B, Abdouh M, Unsain N, Barker PA, Feinstein E, Bernier G, Di Polo A (2013) ASPP1/2 regulate p53-dependent death of retinal ganglion cells through PUMA and Fas/CD95 activation in vivo. J Neurosci 33:2205–2216

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Chen C, Jin N, Zhu J, Kang L, Zhou T, Wang J, Sheng A, Shi J, Gu Z, Sang A (2013a) Muller glia cells activation in rat retina after optic nerve injury: spatiotemporal correlation with transcription initiation factor IIb. J Mol Neurosci 51:37–46

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Yang L, Yu S, Shu Q, Yang C, Wang J, Xu F, Sang A, Liang X (2013) Spatiotemporal changes in NFATc4 expression of retinal ganglion cells after light-Induced damage. J Mol Neurosci

  • Xu Y, Yu S, Shu Q, Yang L, Yang C, Wang J, Xu F, Ji M, Liang X (2014) Upregulation of CREM-1 relates to retinal ganglion cells apoptosis after light-induced damage in vivo. J Mol Neurosci 52:331–338

    Article  CAS  PubMed  Google Scholar 

  • Zacchetti D, Peranen J, Murata M, Fiedler K, Simons K (1995) VIP17/MAL, a proteolipid in apical transport vesicles. FEBS Lett 377:465–469

    Article  CAS  PubMed  Google Scholar 

  • Zhang ZZ, Gong YY, Shi YH, Zhang W, Qin XH, Wu XW (2012) Valproate promotes survival of retinal ganglion cells in a rat model of optic nerve crush. Neuroscience 224:282–293

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Cui Z, Shen A, Li W, Xu G, Bao G, Sun Y, Wang L, Gu H, Zhou Y (2013) Upregulation of myelin and lymphocyte protein (MAL) after traumatic spinal cord injury in rats. J Mol Histol 44:125–134

    Article  CAS  PubMed  Google Scholar 

  • Zou F, Xu J, Fu H, Cao J, Mao H, Gong M, Cui G, Zhang Y, Shi W, Chen J (2013) Different functions of HIPK2 and CtBP2 in traumatic brain injury. J Mol Neurosci 49:395–408

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Specialized Research Foundation for Doctoral Program of Higher Education of China (No. 20120171110086) and Science and Technology Planning Project of Guangzhou China (No. 11C22060787).

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Correspondence to Xiaoling Liang.

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Yongsheng Huang and Yue Xu contributed equally to this work

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Huang, Y., Xu, Y., Cheng, Q. et al. The Expression Changes of Myelin and Lymphocyte Protein (MAL) Following Optic Nerve Crush in Adult Rats Retinal Ganglion Cells. J Mol Neurosci 54, 614–621 (2014). https://doi.org/10.1007/s12031-014-0332-5

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  • DOI: https://doi.org/10.1007/s12031-014-0332-5

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