scholarly journals 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

2010 ◽  
Vol 177 (3) ◽  
pp. 1198-1213 ◽  
Author(s):  
Marianne Pons ◽  
Scott W. Cousins ◽  
Karl G. Csaky ◽  
Gary Striker ◽  
Maria E. Marin-Castaño
Keyword(s):  
Retinal Pigment Epithelium ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cigarette Smoke ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Filamentous Actin ◽  
Actin Reorganization ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

scholarly journals Loss of Extracellular Signal-Regulated Kinase 1/2 in the Retinal Pigment Epithelium Leads to RPE65 Decrease and Retinal Degeneration

2017 ◽  
Vol 37 (24) ◽  
Author(s):  
Aswin Pyakurel ◽  
Delphine Balmer ◽  
Marc K. Saba-El-Leil ◽  
Caroline Kizilyaprak ◽  
Jean Daraspe ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Side Effects ◽  
Retinal Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Rpe Cells ◽  
Extracellular Signal Regulated Kinase ◽  
Ocular Side ◽  
Extracellular Signal

ABSTRACT Recent work suggested that the activity of extracellular signal-regulated kinase 1/2 (ERK1/2) is increased in the retinal pigment epithelium (RPE) of age-related macular degeneration (ARMD) patients and therefore could be an attractive therapeutic target. Notably, ERK1/2 pathway inhibitors are used in cancer therapy, with severe and noncharacterized ocular side effects. To decipher the role of ERK1/2 in RPE cells, we conditionally disrupted the Erk1 and Erk2 genes in mouse RPE. The loss of ERK1/2 activity resulted in a significant decrease in the level of RPE65 expression, a decrease in ocular retinoid levels concomitant with low visual function, and a rapid disorganization of RPE cells, ultimately leading to retinal degeneration. Our results identify the ERK1/2 pathway as a direct regulator of the visual cycle and a critical component of the viability of RPE and photoreceptor cells. Moreover, our results caution about the need for a very fine adjustment of kinase inhibition in cancer or ARMD treatment in order to avoid ocular side effects.

scholarly journals Induction of Heat Shock Protein 70 in Mouse RPE as an In Vivo Model of Transpupillary Thermal Stimulation

2020 ◽  
Vol 21 (6) ◽  
pp. 2063
Author(s):  
Mooud Amirkavei ◽  
Marja Pitkänen ◽  
Ossi Kaikkonen ◽  
Kai Kaarniranta ◽  
Helder André ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Response ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
In Vivo Model ◽  
Tunel Staining ◽  
Long Duration ◽  
Shock Response

The induction of heat shock response in the macula has been proposed as a useful therapeutic strategy for retinal neurodegenerative diseases by promoting proteostasis and enhancing protective chaperone mechanisms. We applied transpupillary 1064 nm long-duration laser heating to the mouse (C57Bl/6J) fundus to examine the heat shock response in vivo. The intensity and spatial distribution of heat shock protein (HSP) 70 expression along with the concomitant probability for damage were measured 24 h after laser irradiation in the mouse retinal pigment epithelium (RPE) as a function of laser power. Our results show that the range of heating powers for producing heat shock response while avoiding damage in the mouse RPE is narrow. At powers of 64 and 70 mW, HSP70 immunostaining indicates 90 and 100% probability for clearly elevated HSP expression while the corresponding probability for damage is 20 and 33%, respectively. Tunel staining identified the apoptotic regions, and the estimated 50% damaging threshold probability for the heating (ED50) was ~72 mW. The staining with Bestrophin1 (BEST1) demonstrated RPE cell atrophy with the most intense powers. Consequently, fundus heating with a long-duration laser provides an approachable method to develop heat shock-based therapies for the RPE of retinal disease model mice.

scholarly journals The Molecular Chaperone Heat Shock Protein 70 Controls Liver Cancer Initiation and Progression by Regulating Adaptive DNA Damage and Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling Pathways

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Wonkyoung Cho ◽  
Xiongjie Jin ◽  
Junfeng Pang ◽  
Yan Wang ◽  
Nahid F. Mivechi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Heat Shock ◽  
Protein Kinase ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Cell Transformation ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

ABSTRACT Delineating the mechanisms that drive hepatic injury and hepatocellular carcinoma (HCC) progression is critical for development of novel treatments for recurrent and advanced HCC but also for the development of diagnostic and preventive strategies. Heat shock protein 70 (HSP70) acts in concert with several cochaperones and nucleotide exchange factors and plays an essential role in protein quality control that increases survival by protecting cells against environmental stressors. Specifically, the HSP70-mediated response has been implicated in the pathogenesis of cancer, but the specific mechanisms by which HSP70 may support malignant cell transformation remains to be fully elucidated. Here, we show that genetic ablation of HSP70 markedly impairs HCC initiation and progression by distinct but overlapping pathways. This includes the potentiation of the carcinogen-induced DNA damage response, at the tumor initiation stage, to increase the p53-dependent surveillance response leading to the cell cycle exit or death of genomically damaged differentiated pericentral hepatocytes, and this may also prevent their conversion into more proliferating HCC progenitor cells. Subsequently, activation of a mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) negative feedback pathway diminishes oncogenic signals, thereby attenuating premalignant cell transformation and tumor progression. Modulation of HSP70 function may be a strategy for interfering with oncogenic signals driving liver cell transformation and tumor progression, thus providing an opportunity for human cancer control.

scholarly journals Phosphorylated Heat Shock Protein 27 Represses Growth of Hepatocellular Carcinoma via Inhibition of Extracellular Signal-regulated Kinase

2008 ◽  
Vol 283 (27) ◽  
pp. 18852-18860 ◽  
Author(s):  
Rie Matsushima-Nishiwaki ◽  
Shinji Takai ◽  
Seiji Adachi ◽  
Chiho Minamitani ◽  
Eisuke Yasuda ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 27 ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal
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