Skip to main content

Advertisement

SpringerLink
Log in

Expression of p97/VCP and ubiquitin during postnatal development of the degenerating rat retina

  • Original Paper
  • Published:
Journal of Molecular Histology Aims and scope Submit manuscript

Abstract

In this study, we aimed to investigate the distribution pattern of ubiquitin and p97/VCP in the rat retina during postnatal development. Eyeballs from 1-, 4-, 10-, 36- and 72-week-old rats were examined by immunohistochemistry, and protein colocalization was determined by immunofluorescence microscopy. In the 1-week-old rat retina, p97/VCP was strongly expressed in the neuroblast layer, however no ubiquitin immunoreactivity was observed. p97/VCP immunoreactivity was present in the ganglion cell layer (GCL), inner nuclear layer (INL), outer nuclear layer (ONL), inner segment (IS) of the photoreceptor layer, and retinal pigment epithelium in the 4- and 10-week-old rat retinas. p97/VCP immunoreactivity increased significantly in the 10-week-old rat retinas. Ubiquitin was barely seen in the 4-week-old rat retinas, and ubiquitin expression was weak in the GCL and the IPL of the 10-week-old rat retinas. In the 36- and 72-week-old rats, the presence of ubiquitin was remarkable in the IS, INL, IPL and GCL, however, p97/VCP immunoreactivity was significantly decreased. Colocalization of ubiquitin and p97/VCP was also observed in the INL, IS, GCL and ONL of 36- and 72-week-old rat retinas. Our results indicate that p97/VCP immunoreactivity in the retina significantly decreases after rats reach 10 weeks of age, whereas ubiquitin immunoreactivity increases with aging. These results suggest that an altered expression pattern of p97/VCP and ubiquitin in the developing rat retina may associate with age-related retinal degeneration.

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

Similar content being viewed by others

References

  • Cayli S, Eyibilen A, Gurbuzler L, Koc S, Atay GA, Ekici A, Aladag I (2011) Jab1 expression is associated with TGF-beta1 signaling in chronic rhinosinusitis and nasal polyposis. Acta Histochem. doi:10.1016/j.acthis.2011.01.005

  • Ciechanover A (2007) Intracellular protein degradation from a vague idea through the lysosome and the ubiquitin-proteasome system and on to human diseases and drug targeting: Nobel Lecture, December 8, 2004. Ann N Y Acad Sci 1116:1–28. doi:10.1196/annals.1402.078

    Article  PubMed  Google Scholar 

  • Curcio CA, Millican CL, Allen KA, Kalina RE (1993) Aging of the human photoreceptor mosaic: evidence for selective vulnerability of rods in central retina. Invest Ophthalmol Vis Sci 34(12):3278–3296

    PubMed  CAS  Google Scholar 

  • Dai RM, Li CC (2001) Valosin-containing protein is a multi-ubiquitin chain-targeting factor required in ubiquitin-proteasome degradation. Nat Cell Biol 3(8):740–744. doi:10.1038/3508705635087056

    Article  PubMed  CAS  Google Scholar 

  • Feeney-Burns L, Hilderbrand ES, Eldridge S (1984) Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells. Invest Ophthalmol Vis Sci 25(2):195–200

    PubMed  CAS  Google Scholar 

  • Ficarro S, Chertihin O, Westbrook VA, White F, Jayes F, Kalab P, Marto JA, Shabanowitz J, Herr JC, Hunt DF, Visconti PE (2003) Phosphoproteome analysis of capacitated human sperm. Evidence of tyrosine phosphorylation of a kinase-anchoring protein 3 and valosin-containing protein/p97 during capacitation. J Biol Chem 278(13):11579–11589. doi:10.1074/jbc.M202325200

    Article  PubMed  CAS  Google Scholar 

  • Finnegan S, Robson J, Hocking PM, Ali M, Inglehearn CF, Stitt A, Curry WJ (2010) Proteomic profiling of the retinal dysplasia and degeneration chick retina. Mol Vis 16:7–17

    PubMed  CAS  Google Scholar 

  • Fletcher EL, Kalloniatis M (1997) Localisation of amino acid neurotransmitters during postnatal development of the rat retina. J Comp Neurol 380(4):449–471. doi:10.1002/(SICI)1096-9861(19970421)380:4<449:AID-CNE3>3.0.CO;2-1

    Article  PubMed  CAS  Google Scholar 

  • Gao H, Hollyfield JG (1992) Aging of the human retina. Differential loss of neurons and retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 33(1):1–17

    PubMed  CAS  Google Scholar 

  • Griciuc A, Aron L, Piccoli G, Ueffing M (2011a) Clearance of Rhodopsin(P23H) aggregates requires the ERAD effector VCP. Biochim Biophys Acta 1803(3):424–434. doi:10.1016/j.bbamcr.2010.01.008

    Article  Google Scholar 

  • Griciuc A, Aron L, Roux MJ, Klein R, Giangrande A, Ueffing M (2011b) Inactivation of VCP/ter94 suppresses retinal pathology caused by misfolded rhodopsin in Drosophila. PLoS Genet 6(8). doi:10.1371/journal.pgen.1001075

  • Grillari J, Katinger H, Voglauer R (2006) Aging and the ubiquitinome: traditional and non-traditional functions of ubiquitin in aging cells and tissues. Exp Gerontol 41(11):1067–1079. doi:10.1016/j.exger.2006.07.003

    Article  PubMed  CAS  Google Scholar 

  • Grunwald JE, Metelitsina TI, Dupont JC, Ying GS, Maguire MG (2005) Reduced foveolar choroidal blood flow in eyes with increasing AMD severity. Invest Ophthalmol Vis Sci 46(3):1033–1038. doi:10.1167/iovs.04-1050

    Article  PubMed  Google Scholar 

  • Harding JJ (2002) Viewing molecular mechanisms of ageing through a lens. Ageing Res Rev 1(3):465–479

    Article  PubMed  CAS  Google Scholar 

  • Hetzer M, Meyer HH, Walther TC, Bilbao-Cortes D, Warren G, Mattaj IW (2001) Distinct AAA-ATPase p97 complexes function in discrete steps of nuclear assembly. Nat Cell Biol 3(12):1086–1091

    Article  PubMed  CAS  Google Scholar 

  • Hirabayashi M, Inoue K, Tanaka K, Nakadate K, Ohsawa Y, Kamei Y, Popiel AH, Sinohara A, Iwamatsu A, Kimura Y, Uchiyama Y, Hori S, Kakizuka A (2001) VCP/p97 in abnormal protein aggregates, cytoplasmic vacuoles, and cell death, phenotypes relevant to neurodegeneration. Cell Death Differ 8(10):977–984. doi:10.1038/sj.cdd.4400907

    Article  PubMed  CAS  Google Scholar 

  • Hochstrasser M (1995) Ubiquitin, proteasomes, and the regulation of intracellular protein degradation. Curr Opin Cell Biol 7(2):215–223

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi T, Manno A, Kakizuka A (2007) Involvement of valosin-containing protein (VCP)/p97 in the formation and clearance of abnormal protein aggregates. Genes Cells 12(7):889–901. doi:10.1111/j.1365-2443.2007.01099.x

    Article  PubMed  CAS  Google Scholar 

  • Kondo H, Rabouille C, Newman R, Levine TP, Pappin D, Freemont P, Warren G (1997) p47 is a cofactor for p97-mediated membrane fusion. Nature 388(6637):75–78

    Article  PubMed  CAS  Google Scholar 

  • Krick R, Bremer S, Welter E, Schlotterhose P, Muehe Y, Eskelinen EL, Thumm M (2010) Cdc48/p97 and Shp1/p47 regulate autophagosome biogenesis in concert with ubiquitin-like Atg8. J Cell Biol 190(6):965–973. doi:10.1083/jcb.201002075

    Article  PubMed  CAS  Google Scholar 

  • Leger F, Fernagut PO, Canron MH, Leoni S, Vital C, Tison F, Bezard E, Vital A (2011) Protein aggregation in the aging retina. J Neuropathol Exp Neurol 70(1):63–68. doi:10.1097/NEN.0b013e31820376cc

    Article  PubMed  CAS  Google Scholar 

  • Lord JM, Roberts LM, Stirling CJ (2005) Quality control: another player joins the ERAD cast. Curr Biol 15(23):R963–R964. doi:10.1016/j.cub.2005.11.013

    Article  PubMed  CAS  Google Scholar 

  • Marshall J (1987) The ageing retina: physiology or pathology. Eye Lond 1(Pt 2):282–295

    Article  PubMed  Google Scholar 

  • Martinez-Vicente M, Sovak G, Cuervo AM (2005) Protein degradation and aging. Exp Gerontol 40(8–9):622–633. doi:10.1016/j.exger.2005.07.005

    Article  PubMed  CAS  Google Scholar 

  • Meyer HH, Shorter JG, Seemann J, Pappin D, Warren G (2000) A complex of mammalian ufd1 and npl4 links the AAA-ATPase, p97, to ubiquitin and nuclear transport pathways. EMBO J 19(10):2181–2192

    Article  PubMed  CAS  Google Scholar 

  • Mirza S, Plafker KS, Aston C, Plafker SM (2010) Expression and distribution of the class III ubiquitin-conjugating enzymes in the retina. Mol Vis 16:2425–2437

    PubMed  CAS  Google Scholar 

  • Ozawa Y, Nakao K, Kurihara T, Shimazaki T, Shimmura S, Ishida S, Yoshimura A, Tsubota K, Okano H (2008) Roles of STAT3/SOCS3 pathway in regulating the visual function and ubiquitin-proteasome-dependent degradation of rhodopsin during retinal inflammation. J Biol Chem 283(36):24561–24570

    Article  PubMed  CAS  Google Scholar 

  • Pickart CM (2001) Ubiquitin enters the new millennium. Mol Cell 8(3):499–504

    Article  PubMed  CAS  Google Scholar 

  • Rabinovich E, Kerem A, Frohlich KU, Diamant N, Bar-Nun S (2002) AAA-ATPase p97/Cdc48p, a cytosolic chaperone required for endoplasmic reticulum-associated protein degradation. Mol Cell Biol 22(2):626–634

    Article  PubMed  CAS  Google Scholar 

  • Ramkumar HL, Zhang J, Chan CC (2010) Retinal ultrastructure of murine models of dry age-related macular degeneration (AMD). Prog Retin Eye Res 29(3):169–190. doi:10.1016/j.preteyeres.2010.02.002

    Article  PubMed  CAS  Google Scholar 

  • Rapaport DH, Wong LL, Wood ED, Yasumura D, LaVail MM (2004) Timing and topography of cell genesis in the rat retina. J Comp Neurol 474(2):304–324. doi:10.1002/cne.20134

    Article  PubMed  Google Scholar 

  • Reddy GB, Vasireddy V, Mandal MN, Tiruvalluru M, Wang XF, Jablonski MM, Nappanveettil G, Ayyagari R (2009) A novel rat model with obesity-associated retinal degeneration. Invest Ophthalmol Vis Sci 50(7):3456–3463. doi:10.1167/iovs.08-2498

    Article  PubMed  Google Scholar 

  • Remé CE, Wolfrum U, Imsand C, Hafezi F, Williams TP (1999) Photoreceptor autophagy: effects of light history on number and opsin content of degradative vacuoles. Invest Ophthalmol Vis Sci 40(10):2398–2404

    PubMed  Google Scholar 

  • Riederer BM, Leuba G, Vernay A, Riederer IM (2011) The role of the ubiquitin proteasome system in Alzheimer’s disease. Exp Biol Med Maywood 236(3):268–276. doi:10.1258/ebm.2010.010327

    Article  PubMed  CAS  Google Scholar 

  • Salvi SM, Akhtar S, Currie Z (2006) Ageing changes in the eye. Postgrad Med J 82(971):581–587. doi:10.1136/pgmj.2005.040857

    Article  PubMed  CAS  Google Scholar 

  • Sati L, Seval-Celik Y, Demir R (2010) Lung surfactant proteins in the early human placenta. Histochem Cell Biol 133 (1):85–93. doi:10.1007/s00418-009-0642-9

    Google Scholar 

  • Sowell RA, Owen JB, Butterfield DA (2009) Proteomics in animal models of Alzheimer’s and Parkinson’s diseases. Ageing Res Rev 8(1):1–17. doi:10.1016/j.arr.2008.07.003

    Article  PubMed  CAS  Google Scholar 

  • Tresse E, Salomons FA, Vesa J, Bott LC, Kimonis V, Yao TP, Dantuma NP, Taylor JP (2010) VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD. Autophagy 6(2):217–227

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson KD (2000) Ubiquitination and deubiquitination: targeting of proteins for degradation by the proteasome. Semin Cell Dev Biol 11(3):141–148. doi:10.1006/scdb.2000.0164

    Article  PubMed  CAS  Google Scholar 

  • Yang S, Liu T, Li S, Zhang X, Ding Q, Que H, Yan X, Wei K, Liu S (2008) Comparative proteomic analysis of brains of naturally aging mice. Neuroscience 154(3):1107–1120. doi:10.1016/j.neuroscience.2008.04.012

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This project was supported by the Research Foundation of Gaziosmanpasa University (Project no:2011-059).

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey

    Huseyin Ortak & Helin Deniz Demir

  2. Department of Histology and Embryology, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey

    Sevil Cayli & Seda Ocakli

  3. Department of Anatomy, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey

    Ufuk Tas

  4. Department of Biochemistry, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey

    Erkan Söğüt

Authors
  1. Huseyin Ortak
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sevil Cayli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ufuk Tas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seda Ocakli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Erkan Söğüt
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Helin Deniz Demir
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Huseyin Ortak.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ortak, H., Cayli, S., Tas, U. et al. Expression of p97/VCP and ubiquitin during postnatal development of the degenerating rat retina. J Mol Hist 43, 17–25 (2012). https://doi.org/10.1007/s10735-011-9374-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10735-011-9374-y

Keywords

Search

Navigation