Cloning of mammalian Ire1 reveals diversity in the ER stress responses

Acidosis Causes Endoplasmic Reticulum Stress and Caspase-12-Mediated Astrocyte Death

“…Caspase-12-mediated astrocyte death K Aoyama et al Ire1-a is broadly expressed, whereas Ire1-b is expressed selectively in foregut-derived epithelium (Tirasophon et al, 1998;Wang et al, 1998). Results of the present study demonstrated a dissociation of Ire1-a from GRP-78 after acidosis, suggesting this as a likely mechanism by which the ER stress response is induced by acidosis.…”

Participation of endoplasmic reticulum stress in the pathogenesis of spontaneous glomerulosclerosis–Role of intra-renal angiotensin system

“…However, activation of IRE1 in the face of persistent ER stress can facilitate apoptosis by promoting the synthesis of proapoptotic proteins. 38 Accordingly, the severity and duration of ER stress determines the success or failure of the ER stress response. 39,40 In addition to participating in the ER stress-induced apoptosis, IRE1 has been shown to promote autophagy in the eukaryotic cells.…”

Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways

“…To determine whether hepatic cholesterol and triglyceride accumulation in hyperhomocysteinemic mice is associated with ER stress and activation of the UPR, we probed total RNA isolated from the livers of CBS +/+ mice fed control or hyperhomocysteinemic diets for GADD153 gene expression (Figure 11), which is a direct indicator of ER stress (41,42). Northern blot analysis demonstrated that steady-state mRNA levels of GADD153 were elevated 6.7-fold in mice fed high-methionine diet and 11.4-fold in mice fed high-methionine/low-folate diet for 2 weeks, compared with control mice (P < 0.05).…”

“…conditions that adversely affect ER function activate the UPR, resulting in increased expression of GRP78/BiP, GRP94 (52-54), GADD153 (41,42), and activation of the ER membrane-bound transcription factor, ATF6 (55). Recent studies have indicated that the UPR regulates lipid biosynthesis in yeast (25,26) and dolichol biosynthesis, which is part of the cholesterol biosynthesis pathway, in human fibroblasts (27).…”