Thursday, August 8, 2013
CRACkdown on pancreatitis.
Gerasimenko et al. have found that blocking calcium release-activated calcium channels (CRACs) could prevent the
calcium (Ca2+)-mediated cytotoxicity that leads to acute
consist of channel subunits such as transmembrane protein 142A
(ORAI1; TMEM142A; CRACM1) and
calcium-sensing sub-units such as stromal interaction molecule 1
et al. propose that in pancreatic acinar cells, high levels of alcohol
lead to formation of fatty acid ethyl esters [a] that cause depletion of
calcium stores in the endoplasmic reticulum [b] and activate STIM1 [c].
STIM1 binds to and activates CRACM1 [d], which then opens to allow
extracellular calcium to flow into the cytoplasm [e], leading to
cytotoxicity, necrosis and pancreatitis [f].
a CRACM1 antagonist developed as a research reagent at GlaxoSmithKline plc for
respiratory indications, prevented acinar cell toxicity caused by fatty acid
CalciMedica Inc. and Synta Pharmaceuticals Corp.
have CRACM1 antagonists in preclinical development for autoimmune and inflammatory