Bax inhibitor-1 protects neurons from oxygen-glucose deprivation.
Bax ihibitor-1 (BI-1) has been characterized as an inhibitor of Bax-induced cell death in plants and various mammalian cell systems. To explore the function of BI-1 in neurons, we overexpressed BI-1 tagged to HA or GFP in rat nigral CSM14.1 and human SH-SY5Y neuroblastoma cells. Stable BI-1 expression proved marked protection from cell death induced by thapsigargine, a stress agent blocking the Ca2+-ATPase of the endoplasmic reticulum (ER) but failed to inhibit cell death induced by staurosporine, a kinase inhibitor initiating mitochondria-dependent apoptosis. Moreover, BI-1 was neuroprotective in a paradigm mimicking ischemia, namely oxygen-glucose as well as serum deprivation. Examination of the subcellular distribution revealed that BI-1 predominantly locates to the ER and nuclear envelope but not mitochondria. Taken together, BI-1 overexpression in the ER is protective in neurons, making BI-1 an interesting target for future studies aiming at the inhibition of neuronal cell death during neurodegenerative diseases and stroke.
Dohm
Christoph P
CP
Department of Neurology, University of Göttingen, 37075 Göttingen, Germany.
Siedenberg
Sandra
S
Liman
Jan
J
Esposito
Alessandro
A
Wouters
Fred S
FS
Reed
John C
JC
Bähr
Mathias
M
Kermer
Pawel
P
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D018696:Neuroprotective Agents; D011993:Recombinant Fusion Proteins; C088008:Tmbim6 protein, rat; D019284:Thapsigargin; D005947:Glucose; D010100:Oxygen