GRP94 reduces cell death in SH-SY5Y cells perturbated calcium homeostasis.
The endoplasmic reticulum (ER) resident-94 kDa glucose-regulated protein (GRP94), plays a pivotal role in cell death due to ER stress. In our study expression of GRP94 was increased in human neuroblastoma SH-SY5Y cells due to exposure to calcium ionophore A23187. A23187-mediated cell death was associated with activation of the major cysteine proteases, caspase-3 and calpain. Pretreatment with adenovirus-mediated antisense GRP94 (AdGRP94AS) reduced viability of SH-SY5Y cells subjected to A23187 treatment compared with wild type cells or cells with adenovirus-mediated overexpression of GRP94 (AdGRP94S). These results indicated that suppression of GRP94 is associated with accelerated cell death. Moreover, expression of GRP94 suppressed A23187-induced cell death and stabilized calcium homeostasis.
Bando
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Y
Department of Anatomy and Neuroscience, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan. ybando@asahikawa-med.ac.jp
Katayama
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T
Aleshin
A N
AN
Manabe
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T
Tohyama
M
M
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D016373:DNA, Antisense / Q000235:genetics; D003620:Dantrolene / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006651:Histocytochemistry; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D007763:Lac Operon / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection
D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; D016373:DNA, Antisense; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C018551:glucose-regulated proteins; D000001:Calcimycin; D019284:Thapsigargin; C505407:CASP3 protein, human; D002154:Calpain; D053148:Caspase 3; D020169:Caspases; D003620:Dantrolene; D002118:Calcium