Correlation of ER stress and retinal degeneration in tubby mice.
Mutation of the Tub gene results in the mislocalization of photoreceptor-specific proteins and eventually retinal degeneration. However, the exact mechanism underlying the retinal degeneration remains largely unknown. In this study, we discovered that the expression of endoplasmic reticulum (ER) stress markers, IRE1, ATF6, eIF2α, GRP78/BiP, and XBP-1, is up regulated during tubby retinal development. The dynamics of the expression of these genes are time-dependent and coincided with the time-course of photoreceptor death. Our data also demonstrated that ER stress triggers apoptosis via down-regulation of Bcl2, up-regulation of CHOP and the activation of NF-кB signaling.
Department of Ophthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States. Electronic address: xue-cai@ouhsc.edu.
Xue
X
Cai
Department of Ophthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States.
Lijuan
L
Chen
Department of Ophthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States; Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States. Electronic address: james-mcginnis@ouhsc.edu.
James F
JF
McGinnis
D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D019084:Fluorescent Antibody Technique, Indirect; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
D051702:Activating Transcription Factor 6; D048868:Adaptor Proteins, Signal Transducing; C497112:Atf6 protein, mouse; D015415:Biomarkers; D004268:DNA-Binding Proteins; C103652:Elf2 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D008565:Membrane Proteins; D014157:Transcription Factors; C098988:Tub protein, mouse; C486556:Ern2 protein, mouse; D017346:Protein Serine-Threonine Kinases
Apoptosis; Downstream regulation; ER stress; Retinal degeneration; Tubby mouse