Exposure of Astrocytes to Hypoxia/Reoxygenation Enhances Expression of Glucose-Regulated Protein 78 Facilitating Astrocyte Release of the Neuroprotective Cytokine Interleukin 6 |
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Authors: | Osamu Hori,&dagger Masayasu Matsumoto,&Dagger Keisuke Kuwabara,Yusuke Maeda,&dagger Hirokazu Ueda,Toshiho Ohtsuki, Taroh Kinoshita,Satoshi Ogawa,&Dagger David M. Stern, Takenobu Kamada |
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Affiliation: | First Department of Medicine and; Department of Neurology, Osaka University Medical School;; Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, Suita City, Japan;and; Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York, U.S.A. |
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Abstract: | Abstract: Astrocytes exposed to hypoxia (H) or hypoxia/reoxygenation (H/R) maintain cell viability and display changes in protein biosynthesis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of metabolically labeled astrocytes exposed to H showed induction of an ≈78-kDa polypeptide that demonstrated sequence identity with glucose-regulated protein (GRP) 78. Cell lysates from H/R astrocytes displayed induction of neuroprotective interleukin (IL) 6, which was present in a high-molecular-weight complex also containing GRP78, suggesting that GRP78 might be functioning as a chaperone during cellular stress consequent on H/R. Introduction of anti-sense oligonucleotide to GRP78 into astrocytes prevented expression of the protein and suppressed H/R-induced astrocyte release of IL-6 by ≈50%. These data indicate that modulation of astrocyte properties during oxygen deprivation results, in part, from intracellular glucose depletion and subsequent expression of GRP78, which sustains generation of neuroprotective IL-6 under the stress of H/R. |
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Keywords: | Stress proteins Oxygen-regulated proteins Cytokine Interleukin 6 |
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