Cigarette smoke-related hydroquinone induces filamentous actin reorganization and heat shock protein 27 phosphorylation through p38 and extracellular signal-regulated kinase 1/2 in retinal pigment epithelium: implications for age-related macular degeneration.

The American Journal of Pathology
Marianne PonsMaria E Marin-Castaño

Abstract

Retinal pigment epithelium (RPE)-derived membranous debris named blebs, may accumulate and contribute to sub-RPE deposit formation, which is the earliest sign of age-related macular degeneration (AMD). Oxidative injury to the RPE might play a significant role in AMD. However, the underlying mechanisms are unknown. We previously reported that hydroquinone (HQ), a major pro-oxidant in cigarette smoke, foodstuff, and atmospheric pollutants, induces actin rearrangement and membrane blebbing in RPE cells as well as sub-RPE deposits in mice. Here, we show for the first time that phosphorylated Heat shock protein 27 (Hsp27), a key regulator of actin filaments dynamics, is up-regulated in RPE from patients with AMD. Also, HQ-induced nonlethal oxidative injury led to Hsp27mRNA up-regulation, dimer formation, and Hsp27 phosphorylation in ARPE-19 cells. Furthermore, we found that a cross talk between p38 and extracellular signal-regulated kinase (ERK) mediates HQ-induced Hsp27 phosphorylation and actin aggregate formation, revealing ERK as a novel upstream mediator of Hsp27 phosphorylation. Finally, we demonstrated that Hsp25, p38, and ERK phosphorylation are increased in aging C57BL/6 mice chronically exposed to HQ, whereas Hsp25 express...Continue Reading

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Citations

Jun 22, 2012·Archives of Toxicology·Cristina Bichels HebedaSandra Helena Poliselli Farsky
Dec 2, 2015·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Claudio RamírezM Cristina Kenney
Apr 21, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yu-Ping JiaLi-Juan Zhang
Mar 21, 2020·International Journal of Molecular Sciences·Niina BhattaraiAnu Kauppinen
Aug 21, 2020·Investigative Ophthalmology & Visual Science·Ping YangGlenn J Jaffe

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