Exposure of astrocytes to hypoxia/reoxygenation enhances expression of glucose-regulated protein 78 facilitating astrocyte release of the neuroprotective cytokine interleukin 6.
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 approximately 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 antisense oligonucleotide to GRP78 into astrocytes prevented expression of the protein and suppressed H/R-induced astrocyte release of IL-6 by approximately 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.
Hori
O
O
First Department of Medicine, Osaka University Medical School, Japan.
Matsumoto
M
M
Kuwabara
K
K
Maeda
Y
Y
Ueda
H
H
Ohtsuki
T
T
Kinoshita
T
T
Ogawa
S
S
Stern
D M
DM
Kamada
T
T
D000818:Animals; D016375:Antisense Elements (Genetics) / Q000235:genetics; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001483:Base Sequence; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D018696:Neuroprotective Agents; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats
D016375:Antisense Elements (Genetics); D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D015850:Interleukin-6; D018832:Molecular Chaperones; D018696:Neuroprotective Agents; D016376:Oligonucleotides, Antisense; D006419:Heme Oxygenase (Decyclizing); D010100:Oxygen