Inflammatory and cell death mechanisms induced by 7-ketocholesterol in the retina. Implications for age-related macular degeneration

Experimental Eye Research
Ana ParienteIgnacio M Larráyoz

Abstract

This review will focus on the inflammatory and toxic mechanism of action of 7-ketocholesterol (7KCh) and the potential implications of its accumulation, especially in the retina. 7KCh is a pro-inflammatory oxysterol usually associated with oxidized lipoprotein deposits present in aged retinas. High amounts of 7KCh can be generated in situ in these lipoprotein deposits possibly through a free radical-mediated mechanism catalyzed by iron. 7KCh seems to activate several kinase signaling pathways that work via multiple transcription factors to induce cytokines and intracellular effectors causing cell death. There seems to be a controversy in the literature in relation to the mechanisms of death induced by 7KCh. Some of the discrepancies arise from the way the oxysterol is delivered because different signaling pathways are activated in different experimental setups. The elucidation of the inflammatory and toxic mechanisms is crucial for the discovery and design of new therapies. Importantly, there is little evidence of 7KCh detoxifying mechanisms in the retina, although some potential enzymes have been described. Thus, continuous formation throughout life and potential toxicity of 7KCh points it out as an "age-related" risk factor i...Continue Reading

References

Feb 22, 1990·The Journal of Comparative Neurology·C A CurcioA E Hendrickson
Feb 1, 1989·Archives of Ophthalmology·E T DobiM Destro
Aug 30, 1994·Proceedings of the National Academy of Sciences of the United States of America·I BjörkhemE Lund
Dec 6, 1993·FEBS Letters·S J FlieslerR K Keller
Nov 17, 1995·Chemistry and Physics of Lipids·S DzeletovicU Diczfalusy
Feb 1, 1996·Experimental Eye Research·K C DunnL M Hjelmeland
Jan 6, 1999·Proceedings of the National Academy of Sciences of the United States of America·B A JanowskiD J Mangelsdorf
May 4, 1999·The International Journal of Biochemistry & Cell Biology·M A Lyons, A J Brown
Apr 5, 2000·The Journal of Biological Chemistry·J Li-HawkinsD W Russell
Jun 16, 2000·Journal of Atherosclerosis and Thrombosis·H HakamataS Horiuchi
Oct 24, 2000·The Journal of Biological Chemistry·J F SavouretR F Casper
Mar 9, 2002·Molecular and Cellular Biology·Sudesh AgrawalGuy M Chisolm
Sep 5, 2002·American Journal of Ophthalmology·Don H AndersonLincoln V Johnson
Sep 20, 2002·Journal of Atherosclerosis and Thrombosis·Yoh MiyashitaKohji Shirai
Nov 27, 2002·Vascular Pharmacology·Wendy JessupLen Kritharides
Jan 14, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Wolfgang DichtlFranz Weidinger
Jan 28, 2003·The American Journal of Pathology·Goldis MalekChristine A Curcio
Apr 30, 2003·Neurochemical Research·John M OngM Cristina Kenney
Dec 4, 2003·Experimental Cell Research·Henrique GirãoAlan Prescott
Mar 12, 2004·American Journal of Ophthalmology·Ronald KleinMylan R Vannewkirk
Jul 28, 2004·Investigative Ophthalmology & Visual Science·Nataliya GordiyenkoIgnacio R Rodriguez
Jul 28, 2004·Investigative Ophthalmology & Visual Science·Ignacio R RodriguezJung Wha Lee
Feb 22, 2005·Redox Report : Communications in Free Radical Research·Makoto ShimozawaToshikazu Yoshikawa
Mar 31, 2005·Rejuvenation Research·Wendy Jessup, Andrew J Brown
Jun 28, 2005·Investigative Ophthalmology & Visual Science·Chuan-Ming LiChristine A Curcio
Nov 16, 2005·Archives of Ophthalmology·Matthew D DavisUNKNOWN Age-Related Eye Disease Study Group
Nov 16, 2005·Archives of Ophthalmology·Frederick L FerrisUNKNOWN Age-Related Eye Disease Study (AREDS) Research Group
Mar 22, 2006·Experimental Eye Research·Jung Wha LeeIgnacio R Rodriguez
Jun 27, 2006·Investigative Ophthalmology & Visual Science·Chuan-Ming LiChristine A Curcio
Jun 29, 2006·Pharmacotherapy·Matthew K ItoSotirios Tsimikas
Nov 24, 2006·Investigative Ophthalmology & Visual Science·Mercedes CamposRobert N Fariss
Jan 9, 2007·Redox Report : Communications in Free Radical Research·David M van ReykWendy Jessup
Mar 10, 2007·Current Molecular Medicine·Maria Norlin, Kjell Wikvall
Mar 10, 2007·Journal of Lipid Research·Hirotoshi FudaCharles A Strott
Apr 25, 2007·Current Eye Research·Corinne JoffreLionel Bretillon
Apr 25, 2007·Current Eye Research·Lionel BretillonCatherine Creuzot-Garcher
Sep 12, 2007·Proceedings of the National Academy of Sciences of the United States of America·Naoki TerasakaAlan R Tall
Oct 9, 2007·Progress in Retinal and Eye Research·Xining HeJoshua L Dunaief
Dec 11, 2007·Microvascular Research·Saurabh LuthraM Cristina Kenney

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Citations

Mar 7, 2020·Biomolecules·Nehal M ElsherbinyAmany Tawfik
Apr 27, 2020·British Journal of Pharmacology·Andrew J BrownMichael J Rogers
Oct 22, 2020·Journal of Lipid Research·Sriganesh Ramachandra Rao, Steven J Fliesler
Mar 5, 2021·Journal of Lipid Research·Sriganesh Ramachandra Rao, Steven J Fliesler
Feb 20, 2021·Molecular and Cellular Endocrinology·Elise P Gomez-Sanchez, Celso E Gomez-Sanchez
Jun 13, 2021·The Journal of Steroid Biochemistry and Molecular Biology·Imen GhzaielGérard Lizard

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