adapt78, a stress-inducible mRNA, is related to the glucose-regulated protein family of genes

We have recently reported a new oxidant- and calcium-inducible mRNA, adapt7 8, from hamster HA-1 cells. The adapt78 mRNA is induced in HA-1 cells under conditions where a protective adaptive response is observed and contains a translatable open reading frame whose protein product shows strong homolog y to a human sequence. Computer analysis of the predicted Adapt78 protein s equence also revealed a stretch of amino acids homologous to a portion of t he glucose-regulated protein78 (Grp78). Based on this homology, we tested t he hypothesis that adapt78 may be a new member of the grp gene family. Towa rd this, we assessed the modulation of adapt78 mRNA by stress agents known to induce grp78. In HA-1 cells, adapt78 mRNA was induced by the calcium ion ophore A23187, 2-deoxyglucose, brefeldin A, tunicamycin, thapsigargin, and cyclopiazonic acid, with thapsigargin being the most potent inducer (7.3-fo ld). As expected, grp78 mRNA was also induced by these agents in our model system. In contrast, heat shock treatment produced little if any modulation of either grp78 or adapt78. Differences were also observed, as adapt78 mRN A but not grp78 mRNA was induced by 160 mu M hydrogen peroxide, and adapt78 demonstrated earlier induction kinetics for certain agents compared with g rp78. adapt78 mRNA was also found to be induced in several different human cell lines. A23187 had the strongest effect on adapt78 mRNA levels in human cells, inducing greater than 20-fold in all human cell cultures tested. Fu rthermore, in vitro transcription translation of human adapt78 cDNA produce d an Adapt78 protein product. We conclude that adapt78 may be a new member of the grp family of genes and may represent an early response grp that com plements the actions of grp78 and grp94. (C) 1999 Academic Press.