Skip to main content

Advertisement

Log in

Expression of c-Jun and Bcl-2 Family Proteins in Apoptotic Photoreceptors of RCS Rats

  • LABORATORY INVESTIGATION
  • Published:
Japanese Journal of Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To determine if c-Jun and Bcl-2 family proteins play a role in photoreceptor apoptosis in Royal College of Surgeons (RCS) rats.

Methods

RCS and Sprague-Dawley rats were used. Cryosections of retinas harvested at various postnatal periods were immunostained with antibodies against c-Jun, Bcl-2, and Bax. Double staining with TdT-dUTP nick-end labeling (TUNEL) or propidium iodide (PI) and antibodies was also done. To study the time course of gene and protein expression, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting analyses were carried out.

Results

TUNEL-positive photoreceptors of RCS rats were stained strongly with antibodies against c-Jun and Bax. The number of immunoreactive cells increased on days 21 and 28 after birth (P21 and P28) and decreased on P45. Semiquantitative RT-PCR analysis showed that mRNAs for c-Jun and Bax were upregulated at P21 and P28, but those for Bcl-2 were unchanged. On immunoblotting, a 43-kDa band was revealed by the anti-c-Jun antibody and a 21-kDa band, by the anti-Bax antibody. Protein expression of c-Jun and Bax were increased at both P21 and P28. The temporal profiles of immunoreactivity, protein expression, and mRNA expression were similar.

Conclusion

c-Jun and Bax may play a role in photoreceptor apoptosis in RCS rats. Jpn J Ophthalmol 2006;50:121–127 © Japanese Ophthalmological Society 2006

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. RJ Mullen MM LaVail (1976) ArticleTitleInherited retinal dystrophy: primary defect in pigment epithelium determined with experimental rat chimeras Science 192 799–801 Occurrence Handle1265483 Occurrence Handle1:STN:280:CSmC2sfgvFQ%3D

    PubMed  CAS  Google Scholar 

  2. MO Tso C Zhang AS Abler et al. (1994) ArticleTitleApoptosis leads to photoreceptor degeneration in inherited retinal dystrophy of RCS rats Invest Ophthalmol Vis Sci 35 2693–2699 Occurrence Handle8188463 Occurrence Handle1:STN:280:ByuB2crksFw%3D

    PubMed  CAS  Google Scholar 

  3. N Katai T Kikuchi H Shibuki et al. (1999) ArticleTitleCaspase-like proteases activated in apoptotic photoreceptors of Royal College of Surgeons rats Invest Ophthalmol Vis Sci 40 1802–1807 Occurrence Handle10393051 Occurrence Handle1:STN:280:DyaK1MzitVahsA%3D%3D

    PubMed  CAS  Google Scholar 

  4. PM D'Cruz D Yasumura J Weir et al. (2000) ArticleTitleMutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat Hum Mol Genet 9 645–651 Occurrence Handle10.1093/hmg/9.4.645 Occurrence Handle10699188

    Article  PubMed  Google Scholar 

  5. PL Cohen R Caricchio V Abraham et al. (2002) ArticleTitleDelayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase J Exp Med 196 135–140 Occurrence Handle12093878 Occurrence Handle1:CAS:528:DC%2BD38Xlt1Whu7g%3D

    PubMed  CAS  Google Scholar 

  6. RS Scott EJ McMahon SM Pop et al. (2001) ArticleTitlePhagocytosis and clearance of apoptotic cells is mediated by MER Nature 411 207–211 Occurrence Handle11346799 Occurrence Handle1:CAS:528:DC%2BD3MXjslGlurs%3D

    PubMed  CAS  Google Scholar 

  7. S Nagata (1997) ArticleTitleApoptosis by death factor Cell 88 355–365 Occurrence Handle10.1016/S0092-8674(00)81874-7 Occurrence Handle9039262 Occurrence Handle1:CAS:528:DyaK2sXhtFahtbg%3D

    Article  PubMed  CAS  Google Scholar 

  8. M Dragunow K Preston (1995) ArticleTitleThe role of inducible transcription factors in apoptotic nerve cell death Brain Res Rev 21 1–28 Occurrence Handle10.1016/0165-0173(95)00003-L Occurrence Handle8547952 Occurrence Handle1:CAS:528:DyaK2MXpvFyqtr8%3D

    Article  PubMed  CAS  Google Scholar 

  9. DT Chao GP Linette LH Boise LS White CB Thompson SJ Korsmeyer (1995) ArticleTitleBcl-XL and Bcl-2 repress a common pathway of cell death J Exp Med 182 821–828 Occurrence Handle10.1084/jem.182.3.821 Occurrence Handle7650488 Occurrence Handle1:CAS:528:DyaK2MXns1Sisr8%3D

    Article  PubMed  CAS  Google Scholar 

  10. A Srinivasan LM Foster MP Testa et al. (1996) ArticleTitleBcl-2 expression in neural cells blocks activation of ICE/CED-3 family proteases during apoptosis J Neurosci 16 5654–5660 Occurrence Handle8795621 Occurrence Handle1:CAS:528:DyaK28XlsFOiurY%3D

    PubMed  CAS  Google Scholar 

  11. TL Deckwerth JL Elliott CM Knudson E Johnson SuffixJr WD Snider SJ Korsmeyer (1996) ArticleTitleBAX is required for neuronal death after trophic factor deprivation and during development Neuron 17 401–411 Occurrence Handle10.1016/S0896-6273(00)80173-7 Occurrence Handle8816704 Occurrence Handle1:STN:280:BymH3MzlsFQ%3D

    Article  PubMed  CAS  Google Scholar 

  12. S Krajewski JK Mai M Krajewska M Sikorska MJ Mossakowski JC Reed (1995) ArticleTitleUpregulation of bax protein levels in neurons following cerebral ischemia J Neurosci 15 6364–6376 Occurrence Handle7472401 Occurrence Handle1:CAS:528:DyaK2MXovFWhtLw%3D

    PubMed  CAS  Google Scholar 

  13. L Wang M Miura L Bergeron H Zhu J Yuan (1994) ArticleTitleIch-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death Cell 78 739–750 Occurrence Handle10.1016/S0092-8674(94)90422-7 Occurrence Handle8087842 Occurrence Handle1:CAS:528:DyaK2cXmvFGgtLk%3D

    Article  PubMed  CAS  Google Scholar 

  14. DS Park L Stefanis C Yan SE Farinelli LA Greene (1996) ArticleTitleOrdering the cell death pathway. Differential effects of BCL2, an interleukin-1-converting enzyme family protease inhibitor, and other survival agents on JNK activation in serum/nerve growth factor-deprived PC12 cells J Biol Chem 271 21898–21905 Occurrence Handle8702992 Occurrence Handle1:CAS:528:DyaK28XlsFKgur0%3D

    PubMed  CAS  Google Scholar 

  15. RW Nickells DJ Zack (1996) ArticleTitleApoptosis in ocular disease: a molecular overview Ophthalmic Genet 17 145–165 Occurrence Handle9010866 Occurrence Handle1:STN:280:ByiC28vhsVc%3D

    PubMed  CAS  Google Scholar 

  16. S Shimizu Y Eguchi W Kamiike H Matsuda Y Tsujimoto (1996) ArticleTitleBcl-2 expression prevents activation of the ICE protease cascade Oncogene 12 2251–2257 Occurrence Handle8649764 Occurrence Handle1:CAS:528:DyaK28XjvFCmt70%3D

    PubMed  CAS  Google Scholar 

  17. V Gagliardini PA Fernandez RK Lee et al. (1994) ArticleTitlePrevention of vertebrate neuronal death by the crmA gene Science 263 826–828 Occurrence Handle8303301 Occurrence Handle1:CAS:528:DyaK2cXhsF2nsrc%3D

    PubMed  CAS  Google Scholar 

  18. F Hafezi JP Steinbach A Marti et al. (1997) ArticleTitleThe absence of c-fos prevents light-induced apoptotic cell death of photoreceptors in retinal degeneration in vivo Nat Med 3 346–349 Occurrence Handle10.1038/nm0397-346 Occurrence Handle9055866 Occurrence Handle1:CAS:528:DyaK2sXhsFGqsbw%3D

    Article  PubMed  CAS  Google Scholar 

  19. J Chen JG Flannery MM La Vail RH Steinberg J Xu MI Simon (1996) ArticleTitlebcl-2 overexpression reduces apoptotic photoreceptor cell death in three different retinal degenerations Proc Natl Acad Sci U S A 93 7042–7047 Occurrence Handle8692941 Occurrence Handle1:CAS:528:DyaK28Xkt1Whtr0%3D

    PubMed  CAS  Google Scholar 

  20. RM Joseph T Li (1996) ArticleTitleOverexpression of Bcl-2 or Bcl-XL transgenes and photoreceptor degeneration Invest Ophthalmol Vis Sci 37 2434–2446 Occurrence Handle8933760 Occurrence Handle1:STN:280:ByiD1cjot1U%3D

    PubMed  CAS  Google Scholar 

  21. T Curran B Franza SuffixJr (1988) ArticleTitleFos and Jun: the AP-1 connection Cell 55 395–397 Occurrence Handle10.1016/0092-8674(88)90024-4 Occurrence Handle3141060 Occurrence Handle1:CAS:528:DyaL1MXivFKk

    Article  PubMed  CAS  Google Scholar 

  22. J Ham C Babij J Whitfield et al. (1995) ArticleTitleA c-Jun dominant negative mutant protects sympathetic neurons against programmed cell death Neuron 14 927–939 Occurrence Handle10.1016/0896-6273(95)90331-3 Occurrence Handle7748560 Occurrence Handle1:CAS:528:DyaK2MXlsl2hs74%3D

    Article  PubMed  CAS  Google Scholar 

  23. CA Haas T Deller T Naumann M Frotscher (1996) ArticleTitleSelective expression of the immediate early gene c-jun in axotomized rat medial septal neurons is not related to neuronal degeneration J Neurosci 16 1894–1903 Occurrence Handle8774457 Occurrence Handle1:CAS:528:DyaK28Xht1GlsLg%3D

    PubMed  CAS  Google Scholar 

  24. MA Soriano I Ferrer E Rodriguez-Farre AM Planas (1996) ArticleTitleApoptosis and c-Jun in the thalamus of the rat following cortical infarction NeuroReport 7 425–428 Occurrence Handle8730797 Occurrence Handle1:CAS:528:DyaK28XisVCmsr4%3D

    PubMed  CAS  Google Scholar 

  25. E Bossy-Wetzel L Bakiri M Yaniv (1997) ArticleTitleInduction of apoptosis by the transcription factor c-Jun EMBO J 16 1695–1709 Occurrence Handle10.1093/emboj/16.7.1695 Occurrence Handle9130714 Occurrence Handle1:CAS:528:DyaK2sXisleqtLk%3D

    Article  PubMed  CAS  Google Scholar 

  26. S Kuroiwa N Katai H Shibuki et al. (1998) ArticleTitleExpression of cell cycle-related genes in dying cells in retinal ischemic injury Invest Ophthalmol Vis Sci 39 610–617 Occurrence Handle9501873 Occurrence Handle1:STN:280:DyaK1c7mt1Gitw%3D%3D

    PubMed  CAS  Google Scholar 

  27. Shibuki H, Katai N, Kuroiwa S, Kurokawa T, Yodoi J, Yoshimura N. Protective effect of adult T-cell leukemia-derived factor on retinal ischemia-reperfusion injury in the rat. Invest Ophthalmol Vis Sci 39:1470–1477

  28. G Martin J Segui P Diaz-Villoslada X Montalban AM Planas I Ferrer (1996) ArticleTitleJun expression is found in neurons located in the vicinity of subacute plaques in patients with multiple sclerosis Neurosci Lett 212 95–98 Occurrence Handle10.1016/0304-3940(96)12776-2 Occurrence Handle8832647 Occurrence Handle1:CAS:528:DyaK28XkvVeqtrw%3D

    Article  PubMed  CAS  Google Scholar 

  29. GM Kasof A Mandelzys SD Maika RE Hammer T Curran JI Morgan (1995) ArticleTitleKainic acid-induced neuronal death is associated with DNA damage and a unique immediate-early gene response in c-fos-lacZ transgenic rats J Neurosci 15 4238–4249 Occurrence Handle7790908 Occurrence Handle1:CAS:528:DyaK2MXmt1aqt7Y%3D

    PubMed  CAS  Google Scholar 

  30. AJ Anderson JH Su CW Cotman (1996) ArticleTitleDNA damage and apoptosis in Alzheimer's disease: colocalization with c-Jun immunoreactivity, relationship to brain area, and effect of postmortem delay J Neurosci 16 1710–1719 Occurrence Handle8774439 Occurrence Handle1:CAS:528:DyaK28Xht1GlsrY%3D

    PubMed  CAS  Google Scholar 

  31. TW Sedlak ZN Oltvai E Yang et al. (1995) ArticleTitleMultiple Bcl-2 family members demonstrate selective dimerizations with Bax Proc Natl Acad Sci U S A 92 7834–7838 Occurrence Handle7644501 Occurrence Handle1:CAS:528:DyaK2MXnsFOnt74%3D

    PubMed  CAS  Google Scholar 

  32. J Mosinger Ogilvie TL Deckwerth CM Knudson SJ Korsmeyer (1998) ArticleTitleSuppression of developmental retinal cell death but not of photoreceptor degeneration in Bax-deficient mice Invest Ophthalmol Vis Sci 39 1713–1720 Occurrence Handle9699561 Occurrence Handle1:STN:280:DyaK1czmtlWnsw%3D%3D

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Naomichi Katai.

About this article

Cite this article

Katai, N., Yanagidaira, T., Senda, N. et al. Expression of c-Jun and Bcl-2 Family Proteins in Apoptotic Photoreceptors of RCS Rats. Jpn J Ophthalmol 50, 121–127 (2006). https://doi.org/10.1007/s10384-005-0296-7

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10384-005-0296-7

Key words

Navigation