BIX

BIX is an inducer of the chaperone protein glucose-regulated protein 78 kDa (GRP78), also known as heat shock 70 kDa protein 5 (HspA5) and immunoglobulin heavy chain-binding protein (BiP).¹ It induces expression of the gene encoding GRP78, but not those encoding calreticulin, CHOP, EDEM, p58^IPK, or ASNA, in SK-N-SH neuroblastoma cells when used at a concentration of 50 µM. BIX (5 µM) reduces endoplasmic reticulum (ER) stress-induced apoptosis in SK-N-SH cells. In vivo, BIX (20 µg/2 µl, i.c.v.) reduces infarct volume and brain swelling in a mouse model of cerebral ischemia induced by middle cerebral artery occlusion (MCAO). It protects against carotid artery occlusion-induced neuronal apoptosis in gerbil hippocampus.² BIX also increases renal GRP78 protein levels and attenuates ischemia and reperfusion-induced renal injury in mice.³

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1. Kudo, T., Kanemoto, S., Hara, H., et al. A molecular chaperone inducer protects neurons from ER stress. Cell Death Differ. 15(2), 364-375 (2008).

2. Oida, Y., Izuta, H., Oyagi, A., et al. Induction of BiP, an ER-resident protein, prevents the neuronal death induced by transient forebrain ischemia in gerbil. Brain Res. 1208, 217-224 (2008).

3. Prachasilchai, W., Sonoda, H., Yokota-Ikeda, N., et al. The protective effect of a newly developed molecular chaperone-inducer against mouse ischemic acute kidney injury. J. Pharmacol. Sci. 109(2), 311-314 (2009).