Skip to main content

Advertisement

SpringerLink
Log in

Upregulation of CREM-1 Relates to Retinal Ganglion Cells Apoptosis After Light-Induced Damage In Vivo

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Previous studies have shown activation of cyclic AMP response element-binding protein (CREB) family is involved in the retinal ganglion cells (RGCs) protection. However, the function of cyclic AMP response element modulator-1 (CREM-1), one member of the CREB family, is still with limited acquaintance. To investigate whether CREM-1 is involved in RGCs death, we performed a light-induced retinal damage model in adult rats. Upregulation of CREM-1 was observed in retina after light-induced damage by performing western blot. Immunofluorescent labeling indicated that upregulated CREM-1 was localized mainly in the RGCs. We also investigated co-localization of CREM-1 with active-caspase-3 and TUNEL (apoptotic markers) in the retina after light-induced damage. In addition, the expression patterns of B cell lymphoma/leukemia-2 and Bcl-2 associated X protein were parallel with that of CREM-1. Collectively, we hypothesized upregulation of CREM-1 in the retina was associated with RGCs death after light-induced damage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Agudo M, Perez-Marin MC, Sobrado-Calvo P, Lonngren U, Salinas-Navarro M, Canovas I, Nadal-Nicolas FM, Miralles-Imperial J, Hallbook F, Vidal-Sanz M (2009) Immediate upregulation of proteins belonging to different branches of the apoptotic cascade in the retina after optic nerve transection and optic nerve crush. Invest Ophthalmol Vis Sci 50:424–431

    Article  PubMed  Google Scholar 

  • Algvere PV, Marshall J, Seregard S (2006) Age-related maculopathy and the impact of blue light hazard. Acta Ophthalmol Scand 84:4–15

    Article  CAS  PubMed  Google Scholar 

  • Bahr M (2000) Live or let die—retinal ganglion cell death and survival during development and in the lesioned adult CNS. Trends Neurosci 23:483–490

    Article  CAS  PubMed  Google Scholar 

  • Benito E, Barco A (2010) CREB’s control of intrinsic and synaptic plasticity: implications for CREB-dependent memory models. Trends Neurosci 33:230–240

    Article  CAS  PubMed  Google Scholar 

  • Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME (1999) Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. Science 286:1358–1362

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Wu W, Dentchev T, Wong R, Dunaief JL (2004) Increased metallothionein in light damaged mouse retinas. Exp Eye Res 79:287–293

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Su Y, Run X, Sun Z, Wang T, Sun S, Liang Z (2013a) Pretreatment of PC12 cells with 17beta-estradiol prevents Abeta-induced down-regulation of CREB phosphorylation and prolongs inhibition of GSK-3beta. J Mol Neurosci 50:394–401

    Article  CAS  PubMed  Google Scholar 

  • Chen Z, Song Y, Yao J, Weng C, Yin ZQ (2013b) Alterations of sodium and potassium channels of RGCs in RCS rat with the development of retinal degeneration. J Mol Neurosci 51(3):976–85

    Article  CAS  PubMed  Google Scholar 

  • Choi JS, Kim JA, Joo CK (2003) Activation of MAPK and CREB by GM1 induces survival of RGCs in the retina with axotomized nerve. Invest Ophthalmol Vis Sci 44:1747–1752

    Article  PubMed  Google Scholar 

  • Chowdhury I, Tharakan B, Bhat GK (2006) Current concepts in apoptosis: the physiological suicide program revisited. Cell Mol Biol Lett 11:506–525

    Article  CAS  PubMed  Google Scholar 

  • Chun H, Hao W, Honghai Z, Ning L, Yasong W, Chen D (2009) CCL3L1 prevents gp120-induced neuron death via the CREB cell signaling pathway. Brain Res 1257:75–88

    Article  CAS  PubMed  Google Scholar 

  • Conforti L, Adalbert R, Coleman MP (2007) Neuronal death: where does the end begin? Trends Neurosci 30:159–166

    Article  CAS  PubMed  Google Scholar 

  • Das A, Garner DP, Del Re AM, Woodward JJ, Kumar DM, Agarwal N, Banik NL, Ray SK (2006) Calpeptin provides functional neuroprotection to rat retinal ganglion cells following Ca2+ influx. Brain Res 1084:146–157

    Article  CAS  PubMed  Google Scholar 

  • Dejda A, Jolivel V, Bourgault S, Seaborn T, Fournier A, Vaudry H, Vaudry D (2008) Inhibitory effect of PACAP on caspase activity in neuronal apoptosis: a better understanding towards therapeutic applications in neurodegenerative diseases. J Mol Neurosci 36:26–37

    Article  CAS  PubMed  Google Scholar 

  • Fan L, Pandey SC, Cohen RS (2008) Estrogen affects levels of Bcl-2 protein and mRNA in medial amygdala of ovariectomized rats. J Neurosci Res 86:3655–3664

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Finkbeiner S (2000) CREB couples neurotrophin signals to survival messages. Neuron 25:11–14

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Ayuso D, Salinas-Navarro M, Agudo-Barriuso M, Alarcon-Martinez L, Vidal-Sanz M, Villegas-Perez MP (2011) Retinal ganglion cell axonal compression by retinal vessels in light-induced retinal degeneration. Mol Vis 17:1716–1733

    PubMed  Google Scholar 

  • Gartner S, Henkind P (1982) Pathology of retinitis pigmentosa. Ophthalmology 89:1425–1432

    Article  CAS  PubMed  Google Scholar 

  • Gordon WC, Casey DM, Lukiw WJ, Bazan NG (2002) DNA damage and repair in light-induced photoreceptor degeneration. Invest Ophthalmol Vis Sci 43:3511–3521

    PubMed  Google Scholar 

  • Guo Z, Du X, Iacovitti L (1998) Regulation of tyrosine hydroxylase gene expression during transdifferentiation of striatal neurons: changes in transcription factors binding the AP-1 site. J Neurosci 18:8163–8174

    CAS  PubMed  Google Scholar 

  • He Z, Jiang J, Kokkinaki M, Golestaneh N, Hofmann MC, Dym M (2008) Gdnf upregulates c-Fos transcription via the Ras/Erk1/2 pathway to promote mouse spermatogonial stem cell proliferation. Stem Cells 26:266–278

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Herdegen T, Leah JD (1998) Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res Brain Res Rev 28:370–490

    Article  CAS  PubMed  Google Scholar 

  • Jancic D, Lopez de Armentia M, Valor LM, Olivares R, Barco A (2009) Inhibition of cAMP response element-binding protein reduces neuronal excitability and plasticity, and triggers neurodegeneration. Cereb Cortex 19:2535–2547

    Article  PubMed  Google Scholar 

  • Johannessen M, Delghandi MP, Moens U (2004) What turns CREB on? Cell Signal 16:1211–1227

    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 

  • Kermer P, Liman J, Weishaupt JH, Bahr M (2004) Neuronal apoptosis in neurodegenerative diseases: from basic research to clinical application. Neurodegener Dis 1:9–19

    Article  PubMed  Google Scholar 

  • Khosravi-Far R, Esposti MD (2004) Death receptor signals to mitochondria. Cancer Biol Ther 3:1051–1057

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kim HS, Park CK (2005) Retinal ganglion cell death is delayed by activation of retinal intrinsic cell survival program. Brain Res 1057:17–28

    Article  CAS  PubMed  Google Scholar 

  • Lonze BE, Ginty DD (2002) Function and regulation of CREB family transcription factors in the nervous system. Neuron 35:605–623

    Article  CAS  PubMed  Google Scholar 

  • Marc RE, Jones BW, Watt CB, Vazquez-Chona F, Vaughan DK, Organisciak DT (2008) Extreme retinal remodeling triggered by light damage: implications for age related macular degeneration. Mol Vis 14:782–806

    PubMed  Google Scholar 

  • Mayor-Torroglosa S, De la Villa P, Rodriguez ME, Lopez-Herrera MP, Aviles-Trigueros M, Garcia-Aviles A, de Imperial JM, Villegas-Perez MP, Vidal-Sanz M (2005) Ischemia results 3 months later in altered ERG, degeneration of inner layers, and deafferented tectum: neuroprotection with brimonidine. Invest Ophthalmol Vis Sci 46:3825–3835

    Article  PubMed  Google Scholar 

  • Men J, Zhang X, Yang Y, Gao D (2012) An AD-related neuroprotector rescues transformed rat retinal ganglion cells from CoCl(2)-induced apoptosis. J Mol Neurosci 47:144–149

    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 

  • Parlato R, Rieker C, Turiault M, Tronche F, Schutz G (2006) Survival of DA neurons is independent of CREM upregulation in absence of CREB. Genesis 44:454–464

    Article  CAS  PubMed  Google Scholar 

  • Parone PA, James D, Martinou JC (2002) Mitochondria: regulating the inevitable. Biochimie 84:105–111

    Article  CAS  PubMed  Google Scholar 

  • Peng Y, Zhang J, Xu H, He J, Ying X, Wang Y (2013) Neuroprotective effect of protease-activated receptor-2 in the hypoxia-induced apoptosis of rat RGC-5 cells. J Mol Neurosci 50:98–108

    Article  CAS  PubMed  Google Scholar 

  • Pereira C, Ferreiro E, Cardoso SM, de Oliveira CR (2004) Cell degeneration induced by amyloid-beta peptides: implications for Alzheimer’s disease. J Mol Neurosci 23:97–104

    Article  CAS  PubMed  Google Scholar 

  • Sakamoto K, Karelina K, Obrietan K (2011) CREB: a multifaceted regulator of neuronal plasticity and protection. J Neurochem 116:1–9

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sanders EJ, Parker E, Harvey S (2008) Growth hormone-mediated survival of embryonic retinal ganglion cells: signaling mechanisms. Gen Comp Endocrinol 156:613–621

    Article  CAS  PubMed  Google Scholar 

  • Sang A, Cheng Y, Lu H, Chen D, Gao R, Shen A (2011) Light-induced retinal ganglion cell damage in vivo involves Dexras1. Mol Vis 17:134–143

    CAS  PubMed  Google Scholar 

  • Sang A, Xu Y, Jin N, Zhou T, Wang J, Zhu J, Chen C, Shi J, Shuai J, Xu G, Gu Z (2013) Involvement of transcription initiation factor IIB in the light-induced death of rat retinal ganglion cells in vivo. J Mol Histol 44:11–18

    Article  CAS  PubMed  Google Scholar 

  • Sawka-Verhelle D, Escoubet-Lozach L, Fong AL, Hester KD, Herzig S, Lebrun P, Glass CK (2004) PE-1/METS, an antiproliferative Ets repressor factor, is induced by CREB-1/CREM-1 during macrophage differentiation. J Biol Chem 279:17772–17784

    Article  CAS  PubMed  Google Scholar 

  • Scott R, Bourtchuladze R, Gossweiler S, Dubnau J, Tully T (2002) CREB and the discovery of cognitive enhancers. J Mol Neurosci 19:171–177

    Article  CAS  PubMed  Google Scholar 

  • Sugiura S, Kitagawa K, Omura-Matsuoka E, Sasaki T, Tanaka S, Yagita Y, Matsushita K, Storm DR, Hori M (2004) CRE-mediated gene transcription in the peri-infarct area after focal cerebral ischemia in mice. J Neurosci Res 75:401–407

    Article  CAS  PubMed  Google Scholar 

  • Wilson BE, Mochon E, Boxer LM (1996) Induction of bcl-2 expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis. Mol Cell Biol 16:5546–5556

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu X, Jin W, Liu X, Fu H, Gong P, Xu J, Cui G, Ni Y, Ke K, Gao Z, Gao Y (2012) Cyclic AMP response element modulator-1 (CREM-1) involves in neuronal apoptosis after traumatic brain injury. J Mol Neurosci 47:357–367

    Article  CAS  PubMed  Google Scholar 

  • Yalcin A, Koulich E, Mohamed S, Liu L, D’Mello SR (2003) Apoptosis in cerebellar granule neurons is associated with reduced interaction between CREB-binding protein and NF-kappaB. J Neurochem 84:397–408

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Odom DT, Koo SH, Conkright MD, Canettieri G, Best J, Chen H, Jenner R, Herbolsheimer E, Jacobsen E, Kadam S, Ecker JR, Emerson B, Hogenesch JB, Unterman T, Young RA, Montminy M (2005) Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci U S A 102:4459–4464

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

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).

Author information

Authors and Affiliations

  1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China

    Yue Xu, Shanshan Yu, Lu Yang, Jiawei Wang, Fan Xu & Xiaoling Liang

  2. Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, People’s Republic of China

    Qinmeng Shu

  3. Department of Ophthalmology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, People’s Republic of China

    Cheng Yang

  4. Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, People’s Republic of China

    Min Ji

Authors
  1. Yue Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shanshan Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qinmeng Shu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lu Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cheng Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jiawei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Min Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xiaoling Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaoling Liang.

Additional information

Yue Xu and Shanshan Yu contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xu, Y., Yu, S., Shu, Q. et al. Upregulation of CREM-1 Relates to Retinal Ganglion Cells Apoptosis After Light-Induced Damage In Vivo. J Mol Neurosci 52, 331–338 (2014). https://doi.org/10.1007/s12031-013-0153-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-013-0153-y

Keywords

Search

Navigation