Endoplasmic reticulum stress upregulates the chondroitin sulfate level which thus prevents neurite extension in C6 glioma cells and primary cultured astrocytes.
Chondroitin sulfate (CS), which is known to be a neurite-preventing molecule, is a major component of the extracellular matrix (ECM) in the central nervous system (CNS). The CS expression is upregulated around damaged areas. Endoplasmic reticulum (ER) stress causes neuronal cell death in numerous neurodegenerative diseases. However, the effects of ER stress on glial cells remain to be clarified. The present study examined whether direct ER stress to glial cells can upregulate CS expression in C6 glioma cells and primary cultured mouse astrocytes, and also whether the expression of CS prevents neurite extension. ER stressors tunicamycin (TM) and thapsigargin (TG) significantly increased CS expression in both C6 cells and primary cultured astrocytes, while NO donor sodium nitroprusside (SNP) did not significantly alter the CS expression. The dosage of TM and TG treatment used in this study did not significantly induce cell death but upregulated the ER chaperone molecule Grp78 in C6 glioma cells and primary astrocytes. The ECM of glial cells exposed to ER stress prevented neurite extension in primary cultured mouse cortical neurons, and chondroitinase ABC (ChABC) treatment diminished the inhibitory effect on neurite extension. These findings suggest that direct ER stress to glial cells increases the CS expression, which thus prevents neurite extension.
Natori
Takamitsu
T
Department of Epigenetic Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, 409-3898, Japan.
Nagai
Kaoru
K
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000648:ultrastructure*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000096:biosynthesis*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005910:Glioma; D051379:Mice; D008810:Mice, Inbred C57BL; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000648:ultrastructure; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology
D000091342:Endoplasmic Reticulum Chaperone BiP; C000717248:Hspa5 protein, mouse; D020030:Nitric Oxide Donors; D014415:Tunicamycin; D009599:Nitroprusside; D019284:Thapsigargin; D002809:Chondroitin Sulfates