Activation of Nuclear Factor-kappaB During Retinal Degeneration in Rd Mice

Overview

Journal Mol Vis

Specialties Cell Biology
Molecular Biology
Ophthalmology

Date 2008 Jun 17

PMID 18552981

Citations 25

Authors

Hui-Yang Zeng

Mark O M Tso

Shenghan Lai

Hong Lai

Affiliations

Soon will be listed here.

Abstract

Purpose: Transcription factors of the nuclear factor-kappa beta (NF-kappaB) family have been demonstrated to play an important role in the regulation of gene expression in the chronic neurodegenerative disorders. The aims of the current study were to investigate the alteration of NF-kappaB activity during retinal degeneration in rd mice and further explore its role in photoreceptor apoptosis.

Methods: Activation of NF-kappaB and its nuclear translocation in the retina of rd mice at postnatal days (P) 8, 10, 12, 14, 16, 18, and 28 were studied by immunohistochemical analysis using NF-kappaB P65 antibody. The amount of NF-kappaB P65 protein and NF-kappaB DNA-binding activity in the whole retina were assessed by western blot analysis and gel shift analysis, respectively. Expression of NF-kappaB in microglial cells labeled with CD11b was determined by double labeling.

Results: NF-kappaB P65 nuclear translocation and its DNA binding activity started to increase in the rd retina at P10 and reached a peak at P12. Expressions of P65 remained at high levels from P12 to P18. Double labeling of P65 with CD11 at P14 showed colocalization of P65 in the microglial cells in the outer nuclear layer.

Conclusions: NF-kappaB was activated in the retinal degeneration of rd mice. NF-kappaB modulation may play a role in the retinal degeneration through microglial activation.

Citing Articles

Cell and molecular targeted therapies for diabetic retinopathy.

Reddy S, Devi V, Seetharaman A, Shailaja S, Bhat K, Gangaraju R Front Endocrinol (Lausanne). 2024; 15:1416668.

PMID: 38948520 PMC: 11211264. DOI: 10.3389/fendo.2024.1416668.

Eye Drop with Fas-Blocking Peptide Attenuates Age-Related Macular Degeneration.

Yi Y, Pyun S, Kim C, Yun G, Kang E, Heo S Cells. 2024; 13(6.

PMID: 38534392 PMC: 10969560. DOI: 10.3390/cells13060548.

The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases.

Varner L, Chaya T, Maeda Y, Tsutsumi R, Zhou S, Tsujii T iScience. 2024; 27(4):109380.

PMID: 38510130 PMC: 10951987. DOI: 10.1016/j.isci.2024.109380.

Ocular Vascular Diseases: From Retinal Immune Privilege to Inflammation.

Wang X, Wang T, Lam E, Alvarez D, Sun Y Int J Mol Sci. 2023; 24(15).

PMID: 37569464 PMC: 10418793. DOI: 10.3390/ijms241512090.

GSK3 Is a Central Player in Retinal Degenerative Diseases but a Challenging Therapeutic Target.

Hottin C, Perron M, Roger J Cells. 2022; 11(18).

PMID: 36139472 PMC: 9496697. DOI: 10.3390/cells11182898.

References

Portera-Cailliau C, Sung C, Nathans J, Adler R . Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa. Proc Natl Acad Sci U S A. 1994; 91(3):974-8. PMC: 521436. DOI: 10.1073/pnas.91.3.974. View

Lee S, Liu W, Dickson D, Brosnan C, Berman J . Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 beta. J Immunol. 1993; 150(7):2659-67. View

Shen Y, Rattan V, Sultana C, Kalra V . Cigarette smoke condensate-induced adhesion molecule expression and transendothelial migration of monocytes. Am J Physiol. 1996; 270(5 Pt 2):H1624-33. DOI: 10.1152/ajpheart.1996.270.5.H1624. View

Mattson M, GOODMAN Y, Luo H, Fu W, Furukawa K . Activation of NF-kappaB protects hippocampal neurons against oxidative stress-induced apoptosis: evidence for induction of manganese superoxide dismutase and suppression of peroxynitrite production and protein tyrosine nitration. J Neurosci Res. 1997; 49(6):681-97. DOI: 10.1002/(SICI)1097-4547(19970915)49:6<681::AID-JNR3>3.0.CO;2-3. View

Camandola S, Mattson M . Pro-apoptotic action of PAR-4 involves inhibition of NF-kappaB activity and suppression of BCL-2 expression. J Neurosci Res. 2000; 61(2):134-9. DOI: 10.1002/1097-4547(20000715)61:2<134::AID-JNR3>3.0.CO;2-P. View

Pawate S, Shen Q, Fan F, Bhat N . Redox regulation of glial inflammatory response to lipopolysaccharide and interferongamma. J Neurosci Res. 2004; 77(4):540-51. DOI: 10.1002/jnr.20180. View

Hunot S, Brugg B, Ricard D, Michel P, Muriel M, Ruberg M . Nuclear translocation of NF-kappaB is increased in dopaminergic neurons of patients with parkinson disease. Proc Natl Acad Sci U S A. 1997; 94(14):7531-6. PMC: 23856. DOI: 10.1073/pnas.94.14.7531. View

Liu X, Samouilov A, Lancaster Jr J, Zweier J . Nitric oxide uptake by erythrocytes is primarily limited by extracellular diffusion not membrane resistance. J Biol Chem. 2002; 277(29):26194-9. DOI: 10.1074/jbc.M201939200. View

Krishnamoorthy R, Crawford M, Chaturvedi M, Jain S, Aggarwal B, Al-Ubaidi M . Photo-oxidative stress down-modulates the activity of nuclear factor-kappaB via involvement of caspase-1, leading to apoptosis of photoreceptor cells. J Biol Chem. 1999; 274(6):3734-43. DOI: 10.1074/jbc.274.6.3734. View

10.

Baeuerle P, Henkel T . Function and activation of NF-kappa B in the immune system. Annu Rev Immunol. 1994; 12:141-79. DOI: 10.1146/annurev.iy.12.040194.001041. View

11.

Farber D . From mice to men: the cyclic GMP phosphodiesterase gene in vision and disease. The Proctor Lecture. Invest Ophthalmol Vis Sci. 1995; 36(2):263-75. View

12.

Tamatani M, Che Y, Matsuzaki H, Ogawa S, Okado H, Miyake S . Tumor necrosis factor induces Bcl-2 and Bcl-x expression through NFkappaB activation in primary hippocampal neurons. J Biol Chem. 1999; 274(13):8531-8. DOI: 10.1074/jbc.274.13.8531. View

13.

Sawada M, Kondo N, Suzumura A, Marunouchi T . Production of tumor necrosis factor-alpha by microglia and astrocytes in culture. Brain Res. 1989; 491(2):394-7. DOI: 10.1016/0006-8993(89)90078-4. View

14.

Zhang W, Stanimirovic D . Current and future therapeutic strategies to target inflammation in stroke. Curr Drug Targets Inflamm Allergy. 2003; 1(2):151-66. DOI: 10.2174/1568010023344689. View

15.

Kaltschmidt C, Kaltschmidt B, Neumann H, Wekerle H, Baeuerle P . Constitutive NF-kappa B activity in neurons. Mol Cell Biol. 1994; 14(6):3981-92. PMC: 358764. DOI: 10.1128/mcb.14.6.3981-3992.1994. View

16.

ONeill L, Kaltschmidt C . NF-kappa B: a crucial transcription factor for glial and neuronal cell function. Trends Neurosci. 1997; 20(6):252-8. DOI: 10.1016/s0166-2236(96)01035-1. View

17.

Colton C, Gilbert D . Production of superoxide anions by a CNS macrophage, the microglia. FEBS Lett. 1987; 223(2):284-8. DOI: 10.1016/0014-5793(87)80305-8. View

18.

Viatour P, Merville M, Bours V, Chariot A . Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation. Trends Biochem Sci. 2005; 30(1):43-52. DOI: 10.1016/j.tibs.2004.11.009. View

19.

Chan E, Murphy J . Reactive oxygen species mediate endotoxin-induced human dermal endothelial NF-kappaB activation. J Surg Res. 2003; 111(1):120-6. DOI: 10.1016/s0022-4804(03)00050-7. View

20.

Shou Y, Li N, Li L, Borowitz J, Isom G . NF-kappaB-mediated up-regulation of Bcl-X(S) and Bax contributes to cytochrome c release in cyanide-induced apoptosis. J Neurochem. 2002; 81(4):842-52. DOI: 10.1046/j.1471-4159.2002.00880.x. View