Effect of glucose concentration on activation of the ASK1–SEK1–JNK1 signal transduction pathway

Abstract

Recently, acute total glucose deprivation has been shown to cause activation of ASK1–MEK–MAPK signal transduction and dissociation of glutaredoxin (GRX) from apoptosis signal-regulating kinase 1 (ASK1). In this study, we investigated whether clinically relevant concentrations (0.01–0.1 mM) of glucose promote ASK1 activation. We observed that a prominent activation of JNK1 occurred at a glucose concentration less than or equal to 0.01 mM. Similar to JNK1 activation, we also observed that low glucose-induced ASK1 activation, dissociation of GRX and thioredoxin (TRX) from ASK1, dimerization of ASK1, and association of Daxx and TRAF2 with ASK1 significantly occurred at a glucose concentration less than or equal to 0.01 mM.