Iron Toxicity in the Retina Requires Alu RNA and the NLRP3 Inflammasome

Cell Reports

Volumn 11, Issue 11, 2015, Pages 1686-1693

  Gelfand, Bradley D ^a,b,c   Wright, Charles B ^a   Kim, Younghee ^a   Yasuma, Tetsuhiro ^a   Yasuma, Reo ^a   Li, Shengjian ^a   Fowler, Benjamin J ^a   Bastos Carvalho, Ana ^a   Kerur, Nagaraj ^a   Uittenbogaard, Annette ^a   Han, Youn Seon ^a   Lou, Dingyuan ^a   Kleinman, Mark E ^a   McDonald, W Hayes ^d   Núñez, Gabriel ^e   Georgel, Philippe ^f   Dunaief, Joshua L ^g   Ambati, Jayakrishna ^a  

^a UNIVERSITY OF KENTUCKY   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

^c UNIVERSITY OF KENTUCKY   (United States)

^d VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^f UNIVERSITÉ DE STRASBOURG   (France)

^g UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BINDING PROTEIN; CASPASE 11; CRYOPYRIN; DICER; DICER1; FERROUS GLUCONATE; INFLAMMASOME; INTERLEUKIN 1BETA CONVERTING ENZYME; IRON; POLYCYTIDYLIC ACID BINDING PROTEIN 2; RNA; UNCLASSIFIED DRUG; CARRIER PROTEIN; DEAD BOX PROTEIN; DICER1 PROTEIN, MOUSE; NLRP3 PROTEIN, MOUSE; PCBP2 PROTEIN, MOUSE; RIBONUCLEASE III; RNA BINDING PROTEIN;

AGE RELATED MACULAR DEGENERATION; ALU SEQUENCE; ANIMAL TISSUE; ARTICLE; CATALYSIS; CONTROLLED STUDY; DEGENERATIVE DISEASE; DISEASE ASSOCIATION; GENE TARGETING; INNATE IMMUNITY; IRON OVERLOAD; MOUSE; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN INDUCTION; PROTEIN SYNTHESIS INHIBITION; RETINA PIGMENT DEGENERATION; RNA ANALYSIS; RNA TRANSCRIPTION; SHORT INTERSPERSED REPEAT; ANIMAL; C57BL MOUSE; DRUG EFFECTS; GENETICS; METABOLISM; RETINAL PIGMENT EPITHELIUM;

MUS; RODENTIA;

ALU ELEMENTS; ANIMALS; CARRIER PROTEINS; CASPASE 1; DEAD-BOX RNA HELICASES; INFLAMMASOMES; IRON; MICE; MICE, INBRED C57BL; NLR FAMILY, PYRIN DOMAIN-CONTAINING 3 PROTEIN; RETINAL PIGMENT EPITHELIUM; RIBONUCLEASE III; RNA-BINDING PROTEINS;

EID: 84937630554     PISSN: None     EISSN: 22111247     Source Type: Journal    
DOI: 10.1016/j.celrep.2015.05.023     Document Type: Article

References (49)

1. Anderson O.A., Finkelstein A., Shima D.T. A2E induces IL-1ß production in retinal pigment epithelial cells via the NLRP3 inflammasome. PLoS ONE 2013, 8:e67263.
2. Ayton S., Lei P. Nigral iron elevation is an invariable feature of Parkinson's disease and is a sufficient cause of neurodegeneration. BioMed Res. Int. 2014, 2014:581256.
3. Blyn L.B., Swiderek K.M., Richards O., Stahl D.C., Semler B.L., Ehrenfeld E. Poly(rC) binding protein 2 binds to stem-loop IV of the poliovirus RNA 5' noncoding region: identification by automated liquid chromatography-tandem mass spectrometry. Proc. Natl. Acad. Sci. USA 1996, 93:11115-11120.
4. Blyn L.B., Towner J.S., Semler B.L., Ehrenfeld E. Requirement of poly(rC) binding protein 2 for translation of poliovirus RNA. J. Virol. 1997, 71:6243-6246.
5. Chan C., Shen D., Wang Y., Chu X., Abu-Asab M., Tuo J. Inflammasomes in human eyes with AMD and mouse retinas with focal retinal degeneration 2013, ARVO Annual Meeting, Seattle, WA. http://www.arvo.org/webs/am2013/abstract/section/retinal_cell_biology.pdf.
6. Codolo G., Plotegher N., Pozzobon T., Brucale M., Tessari I., Bubacco L., de Bernard M. Triggering of inflammasome by aggregated α-synuclein, an inflammatory response in synucleinopathies. PLoS ONE 2013, 8:e55375.
7. Czyzyk-Krzeska M.F., Bendixen A.C. Identification of the poly(C) binding protein in the complex associated with the 3' untranslated region of erythropoietin messenger RNA. Blood 1999, 93:2111-2120.
8. Dexter D.T., Wells F.R., Agid F., Agid Y., Lees A.J., Jenner P., Marsden C.D. Increased nigral iron content in postmortem parkinsonian brain. Lancet 1987, 2:1219-1220.
9. Doyle S.L., Campbell M., Ozaki E., Salomon R.G., Mori A., Kenna P.F., Farrar G.J., Kiang A.S., Humphries M.M., Lavelle E.C., et al. NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components. Nat. Med. 2012, 18:791-798.
10. Dridi S., Hirano Y., Tarallo V., Kim Y., Fowler B.J., Ambati B.K., Bogdanovich S., Chiodo V.A., Hauswirth W.W., Kugel J.F., et al. ERK1/2 activation is a therapeutic target in age-related macular degeneration. Proc. Natl. Acad. Sci. USA 2012, 109:13781-13786.
11. Flinn J.M., Kakalec P., Tappero R., Jones B., Lengyel I. Correlations in distribution and concentration of calcium, copper and iron with zinc in isolated extracellular deposits associated with age-related macular degeneration. Metallomics 2014, 6:1223-1228.
12. Fowler B.J., Gelfand B.D., Kim Y., Kerur N., Tarallo V., Hirano Y., Amarnath S., Fowler D.H., Radwan M., Young M.T., et al. Nucleoside reverse transcriptase inhibitors possess intrinsic anti-inflammatory activity. Science 2014, 346:1000-1003.
13. Freeman D., Cedillos R., Choyke S., Lukic Z., McGuire K., Marvin S., Burrage A.M., Sudholt S., Rana A., O'Connor C., et al. Alpha-synuclein induces lysosomal rupture and cathepsin dependent reactive oxygen species following endocytosis. PLoS ONE 2013, 8:e62143.
14. Ghosh D., Srivastava G.P., Xu D., Schulz L.C., Roberts R.M. A link between SIN1 (MAPKAP1) and poly(rC) binding protein 2 (PCBP2) in counteracting environmental stress. Proc. Natl. Acad. Sci. USA 2008, 105:11673-11678.
15. Gnana-Prakasam J.P., Tawfik A., Romej M., Ananth S., Martin P.M., Smith S.B., Ganapathy V. Iron-mediated retinal degeneration in haemojuvelin-knockout mice. Biochem. J. 2012, 441:599-608.
16. Hadziahmetovic M., Dentchev T., Song Y., Haddad N., He X., Hahn P., Pratico D., Wen R., Harris Z.L., Lambris J.D., et al. Ceruloplasmin/hephaestin knockout mice model morphologic and molecular features of AMD. Invest. Ophthalmol. Vis. Sci. 2008, 49:2728-2736.
17. Hahn P., Milam A.H., Dunaief J.L. Maculas affected by age-related macular degeneration contain increased chelatable iron in the retinal pigment epithelium and Bruch's membrane. Arch. Ophthalmol. 2003, 121:1099-1105.
18. Hahn P., Qian Y., Dentchev T., Chen L., Beard J., Harris Z.L., Dunaief J.L. Disruption of ceruloplasmin and hephaestin in mice causes retinal iron overload and retinal degeneration with features of age-related macular degeneration. Proc. Natl. Acad. Sci. USA 2004, 101:13850-13855.
19. Han W., Xin Z., Zhao Z., Bao W., Lin X., Yin B., Zhao J., Yuan J., Qiang B., Peng X. RNA-binding protein PCBP2 modulates glioma growth by regulating FHL3. J. Clin. Invest. 2013, 123:2103-2118.
20. Heneka M.T., Kummer M.P., Stutz A., Delekate A., Schwartz S., Vieira-Saecker A., Griep A., Axt D., Remus A., Tzeng T.C., et al. NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 2013, 493:674-678.
21. Hu Q., Tanasa B., Trabucchi M., Li W., Zhang J., Ohgi K.A., Rose D.W., Glass C.K., Rosenfeld M.G. DICER- and AGO3-dependent generation of retinoic acid-induced DR2 Alu RNAs regulates human stem cell proliferation. Nat. Struct. Mol. Biol. 2012, 19:1168-1175.
22. Hu C.E., Liu Y.C., Zhang H.D., Huang G.J. The RNA-binding protein PCBP2 facilitates gastric carcinoma growth by targeting miR-34a. Biochem. Biophys. Res. Commun. 2014, 448:437-442.
23. Jünemann A.G., Stopa P., Michalke B., Chaudhri A., Reulbach U., Huchzermeyer C., Schlötzer-Schrehardt U., Kruse F.E., Zrenner E., Rejdak R. Levels of aqueous humor trace elements in patients with non-exsudative age-related macular degeneration: a case-control study. PLoS ONE 2013, 8:e56734.
24. Jurka J., Kohany O., Pavlicek A., Kapitonov V.V., Jurka M.V. Clustering, duplication and chromosomal distribution of mouse SINE retrotransposons. Cytogenet. Genome Res. 2005, 110:117-123.
25. Kaneko H., Dridi S., Tarallo V., Gelfand B.D., Fowler B.J., Cho W.G., Kleinman M.E., Ponicsan S.L., Hauswirth W.W., Chiodo V.A., et al. DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration. Nature 2011, 471:325-330.
26. Kauppinen A., Niskanen H., Suuronen T., Kinnunen K., Salminen A., Kaarniranta K. Oxidative stress activates NLRP3 inflammasomes in ARPE-19 cells-implications for age-related macular degeneration (AMD). Immunol. Lett. 2012, 147:29-33.
27. Kerur N., Hirano Y., Tarallo V., Fowler B.J., Bastos-Carvalho A., Yasuma T., Yasuma R., Kim Y., Hinton D.R., Kirschning C.J., et al. TLR-independent and P2X7-dependent signaling mediate Alu RNA-induced NLRP3 inflammasome activation in geographic atrophy. Invest. Ophthalmol. Vis. Sci. 2013, 54:7395-7401.
28. Lane D.J., Richardson D.R. Chaperone turns gatekeeper: PCBP2 and DMT1 form an iron-transport pipeline. Biochem. J. 2014, 462:e1-e3.
29. Li Y., Lin L., Li Z., Ye X., Xiong K., Aryal B., Xu Z., Paroo Z., Liu Q., He C., Jin P. Iron homeostasis regulates the activity of the microRNA pathway through poly(C)-binding protein 2. Cell Metab. 2012, 15:895-904.
30. Lin M., Rippe R.A., Niemelä O., Brittenham G., Tsukamoto H. Role of iron in NF-kappa B activation and cytokine gene expression by rat hepatic macrophages. Am. J. Physiol. 1997, 272:G1355-G1364.
31. Liu R.T., Gao J., Cao S., Sandhu N., Cui J.Z., Chou C.L., Fang E., Matsubara J.A. Inflammatory mediators induced by amyloid-beta in the retina and RPE in vivo: implications for inflammasome activation in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2013, 54:2225-2237.
32. Marneros A.G. NLRP3 inflammasome blockade inhibits VEGF-A-induced age-related macular degeneration. Cell Rep. 2013, 4:945-958.
33. Mori M.A., Raghavan P., Thomou T., Boucher J., Robida-Stubbs S., Macotela Y., Russell S.J., Kirkland J.L., Blackwell T.K., Kahn C.R. Role of microRNA processing in adipose tissue in stress defense and longevity. Cell Metab. 2012, 16:336-347.
34. Paulding W.R., Czyzyk-Krzeska M.F. Regulation of tyrosine hydroxylase mRNA stability by protein-binding, pyrimidine-rich sequence in the 3'-untranslated region. J. Biol. Chem. 1999, 274:2532-2538.
35. Quintana C., Bellefqih S., Laval J.Y., Guerquin-Kern J.L., Wu T.D., Avila J., Ferrer I., Arranz R., Patiño C. Study of the localization of iron, ferritin, and hemosiderin in Alzheimer's disease hippocampus by analytical microscopy at the subcellular level. J. Struct. Biol. 2006, 153:42-54.
36. Ren Y.F., Li G., Wu J., Xue Y.F., Song Y.J., Lv L., Zhang X.J., Tang K.F. Dicer-dependent biogenesis of small RNAs derived from 7SL RNA. PLoS ONE 2012, 7:e40705.
37. Ren Y.F., Li G., Xue Y.F., Zhang X.J., Song Y.J., Lv L., Wu J., Fang Y.X., Wang Y.Q., Shi K.Q., et al. Decreased dicer expression enhances SRP-mediated protein targeting. PLoS ONE 2013, 8:e56950.
38. Sayre L.M., Perry G., Harris P.L., Liu Y., Schubert K.A., Smith M.A. In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer's disease: a central role for bound transition metals. J. Neurochem. 2000, 74:270-279.
39. Smith M.A., Harris P.L., Sayre L.M., Perry G. Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc. Natl. Acad. Sci. USA 1997, 94:9866-9868.
40. Tarallo V., Hirano Y., Gelfand B.D., Dridi S., Kerur N., Kim Y., Cho W.G., Kaneko H., Fowler B.J., Bogdanovich S., et al. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell 2012, 149:847-859.
41. Triantafilou K., Hughes T.R., Triantafilou M., Morgan B.P. The complement membrane attack complex triggers intracellular Ca2+ fluxes leading to NLRP3 inflammasome activation. J. Cell Sci. 2013, 126:2903-2913.
42. Tseng W.A., Thein T., Kinnunen K., Lashkari K., Gregory M.S., D'Amore P.A., Ksander B.R. NLRP3 inflammasome activation in retinal pigment epithelial cells by lysosomal destabilization: implications for age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 2013, 54:110-120.
43. Urrutia P.J., Mena N.P., Núñez M.T. The interplay between iron accumulation, mitochondrial dysfunction, and inflammation during the execution step of neurodegenerative disorders. Front. Pharmacol. 2014, 5:38.
44. Waggoner S.A., Johannes G.J., Liebhaber S.A. Depletion of the poly(C)-binding proteins alphaCP1 and alphaCP2 from K562 cells leads to p53-independent induction of cyclin-dependent kinase inhibitor (CDKN1A) and G1 arrest. J. Biol. Chem. 2009, 284:9039-9049.
45. Wiesen J.L., Tomasi T.B. Dicer is regulated by cellular stresses and interferons. Mol. Immunol. 2009, 46:1222-1228.
46. Xin Z., Han W., Zhao Z., Xia Q., Yin B., Yuan J., Peng X. PCBP2 enhances the antiviral activity of IFN-α against HCV by stabilizing the mRNA of STAT1 and STAT2. PLoS ONE 2011, 6:e25419.
47. Xiong S., She H., Zhang A.S., Wang J., Mkrtchyan H., Dynnyk A., Gordeuk V.R., French S.W., Enns C.A., Tsukamoto H. Hepatic macrophage iron aggravates experimental alcoholic steatohepatitis. Am. J. Physiol. Gastrointest. Liver Physiol. 2008, 295:G512-G521.
48. Yan Y., Salazar T.E., Dominguez J.M., Nguyen D.V., Li Calzi S., Bhatwadekar A.D., Qi X., Busik J.V., Boulton M.E., Grant M.B. Dicer expression exhibits a tissue-specific diurnal pattern that is lost during aging and in diabetes. PLoS ONE 2013, 8:e80029.
49. You F., Sun H., Zhou X., Sun W., Liang S., Zhai Z., Jiang Z. PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4. Nat. Immunol. 2009, 10:1300-1308.