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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.

Publication ,  Journal Article
Pons, M; Cousins, SW; Csaky, KG; Striker, G; Marin-Castaño, ME
Published in: Am J Pathol
September 2010

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 expression is decreased. Our data suggest that phosphorylated Hsp27 might be a key mediator in AMD and HQ-induced oxidative injury to the RPE, which may provide helpful insights into the early cellular events associated with actin reorganization and bleb formation involved in sub-RPE deposits formation relevant to the pathogenesis of AMD.

Duke Scholars

Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

September 2010

Volume

177

Issue

3

Start / End Page

1198 / 1213

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Statistics, Nonparametric
  • Smoking
  • Reverse Transcriptase Polymerase Chain Reaction
  • Retinal Pigment Epithelium
  • Phosphorylation
  • Pathology
  • Middle Aged
  • Mice
  • Male
 

Citation

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Pons, Marianne, Scott W. Cousins, Karl G. Csaky, Gary Striker, and Maria E. Marin-Castaño. “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.Am J Pathol 177, no. 3 (September 2010): 1198–1213. https://doi.org/10.2353/ajpath.2010.091108.
Journal cover image

Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

September 2010

Volume

177

Issue

3

Start / End Page

1198 / 1213

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Statistics, Nonparametric
  • Smoking
  • Reverse Transcriptase Polymerase Chain Reaction
  • Retinal Pigment Epithelium
  • Phosphorylation
  • Pathology
  • Middle Aged
  • Mice
  • Male