Induction of BiP, an ER-resident protein, prevents the neuronal death induced by transient forebrain ischemia in gerbil

Endoplasmic reticulum (ER) stress, which is caused by the accumulation of unfolded proteins in the ER lumen, is associated with stroke and neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. We evaluated the effect of a selective inducer of immunoglobulin heavy chain binding protein (BiP) (BiP inducer X; BIX) against both tunicamycin-induced cell death (in SH-SY5Y cells) and the effects of global transient forebrain ischemia (in gerbils). BIX significantly induced BiP expression both in vitro and in vivo. Pretreatment with BIX at 2 or 5 microM reduced the cell death induced by tunicamycin in SH-SY5Y cells. In gerbils subjected to forebrain ischemia, prior treatment with BIX (intracerebroventricular injection at 10 or 40 microg) protected against cell death and decreased TUNEL-positive cells in the hippocampal CA1 subfield. These findings indicate that this selective inducer of BiP could be used to prevent the neuronal damage both in vitro and in vivo.