Protective role of Gipie, a Girdin family protein, in endoplasmic reticulum stress responses in endothelial cells
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- Etsushi Matsushita
- Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan
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- Naoya Asai
- Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan
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- Atsushi Enomoto
- Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan
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- Yoshiyuki Kawamoto
- Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi 487–8501, Japan
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- Takuya Kato
- Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan
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- Shinji Mii
- Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan
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- Kengo Maeda
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan
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- Rei Shibata
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan
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- Shun Hattori
- Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan
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- Minako Hagikura
- Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan
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- Ken Takahashi
- Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan
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- Masahiro Sokabe
- Department of Physiology, Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan
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- Yoshiki Murakumo
- Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan
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- Toyoaki Murohara
- Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan
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- Masahide Takahashi
- Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466–8550, Japan
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- Jeffrey L. Brodsky
- editor
Description
<jats:p> Continued exposure of endothelial cells to mechanical/shear stress elicits the unfolded protein response (UPR), which enhances intracellular homeostasis and protect cells against the accumulation of improperly folded proteins. Cells commit to apoptosis when subjected to continuous and high endoplasmic reticulum (ER) stress unless homeostasis is maintained. It is unknown how endothelial cells differentially regulate the UPR. Here we show that a novel Girdin family protein, Gipie (78 kDa glucose-regulated protein [GRP78]-interacting protein induced by ER stress), is expressed in endothelial cells, where it interacts with GRP78, a master regulator of the UPR. Gipie stabilizes the interaction between GRP78 and the ER stress sensor inositol-requiring protein 1 (IRE1) at the ER, leading to the attenuation of IRE1-induced c-Jun N-terminal kinase (JNK) activation. Gipie expression is induced upon ER stress and suppresses the IRE1-JNK pathway and ER stress-induced apoptosis. Furthermore we found that Gipie expression is up-regulated in the neointima of carotid arteries after balloon injury in a rat model that is known to result in the induction of the UPR. Thus our data indicate that Gipie/GRP78 interaction controls the IRE1-JNK signaling pathway. That interaction appears to protect endothelial cells against ER stress-induced apoptosis in pathological contexts such as atherosclerosis and vascular endothelial dysfunction. </jats:p>
Journal
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- Molecular Biology of the Cell
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Molecular Biology of the Cell 22 (6), 736-747, 2011-03-15
American Society for Cell Biology (ASCB)
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Keywords
- Male
- Vesicular Transport Proteins
- Golgi Apparatus
- Apoptosis
- Protein Serine-Threonine Kinases
- Endoplasmic Reticulum
- Chlorocebus aethiops
- Endoribonucleases
- Animals
- Humans
- Rats, Wistar
- Endoplasmic Reticulum Chaperone BiP
- Cells, Cultured
- Heat-Shock Proteins
- Microfilament Proteins
- JNK Mitogen-Activated Protein Kinases
- Endothelial Cells
- Membrane Proteins
- Articles
- U937 Cells
- Rats
- Enzyme Activation
- COS Cells
- Unfolded Protein Response
- RNA Interference
- Stress, Mechanical
- Carrier Proteins
- Signal Transduction
Details 詳細情報について
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- CRID
- 1360565167444979200
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- ISSN
- 19394586
- 10591524
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- PubMed
- 21289099
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- Article Type
- journal article
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- Data Source
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- Crossref
- KAKEN
- OpenAIRE
