TY - JOUR
T1 - Activation of endoplasmic reticulum stress in degenerating photoreceptors of the rd1 mouse
AU - Yang, Li Ping
AU - Wu, Le Meng
AU - Guo, Xiu Juan
AU - Tso, Mark O.M.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/11
Y1 - 2007/11
N2 - PURPOSE. Endoplasmic reticulum (ER) stress has been implicated in a wide variety of neurodegenerative disorders of the central nervous system (CNS). This study was designed to elucidate the role of ER stress in photoreceptor apoptosis in the rd1 mouse. METHODS. Photoreceptor apoptosis in the rd1 mouse was detected by terminal dUTP transferase nick-end labeling (TUNEL). Protein expressions of ER stress sensors, including glucose-regulated protein-78 (GRP78/BiP), caspase-12, phospho-eukaryotic initiation factor 2α (eIF2α), and phospho-pancreatic ER kinase (PERK), were examined by immunofluorescence and Western blot assays. RESULTS. Accompanying photoreceptor apoptosis in the rd1 mouse, the protein expressions of GRP78/BiP, caspase-12, phospho-eIF2α, and phospho-PERK were upregulated in a time-dependent manner. The upregulation of these proteins coincided with or preceded photoreceptor apoptosis. At the peak of their expression, these proteins were primarily located in the photoreceptor inner segments, the outer nuclear layer, or both. CONCLUSIONS. ER stress plays an important role in photoreceptor apoptosis in the rd1 mouse. Therefore, ER stress modulators may be strong candidates as therapeutic agents in the treatment of retinal degenerative diseases.
AB - PURPOSE. Endoplasmic reticulum (ER) stress has been implicated in a wide variety of neurodegenerative disorders of the central nervous system (CNS). This study was designed to elucidate the role of ER stress in photoreceptor apoptosis in the rd1 mouse. METHODS. Photoreceptor apoptosis in the rd1 mouse was detected by terminal dUTP transferase nick-end labeling (TUNEL). Protein expressions of ER stress sensors, including glucose-regulated protein-78 (GRP78/BiP), caspase-12, phospho-eukaryotic initiation factor 2α (eIF2α), and phospho-pancreatic ER kinase (PERK), were examined by immunofluorescence and Western blot assays. RESULTS. Accompanying photoreceptor apoptosis in the rd1 mouse, the protein expressions of GRP78/BiP, caspase-12, phospho-eIF2α, and phospho-PERK were upregulated in a time-dependent manner. The upregulation of these proteins coincided with or preceded photoreceptor apoptosis. At the peak of their expression, these proteins were primarily located in the photoreceptor inner segments, the outer nuclear layer, or both. CONCLUSIONS. ER stress plays an important role in photoreceptor apoptosis in the rd1 mouse. Therefore, ER stress modulators may be strong candidates as therapeutic agents in the treatment of retinal degenerative diseases.
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U2 - 10.1167/iovs.07-0512
DO - 10.1167/iovs.07-0512
M3 - Article
C2 - 17962473
AN - SCOPUS:38449086823
SN - 0146-0404
VL - 48
SP - 5191
EP - 5198
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 11
ER -