earticle

영어

Murine inositol-requiring enzyme 1 alpha (IRE1α) appears to function as a proximal sensor of the endoplasmic reticulum (ER) stress. To test if IRE1α has any functional role during the dieldrin-induced ER response and subsequent apoptosis, first, the wild type IRE1α cDNA and a mutant IRE1α lacking the c-terminal kinase domain (ΔIRE1α) were isolated by RT-PCR cloning, which is the routine cDNA cloning procedure. After cloning into the expression vector (pFLAG-CMV), their protective or apoptotic effects were tested by transient expression analysis under
normal and dieldrin-treatment conditions. Dopaminergic neuronal cells expressing ΔIRE1α showed lower expression of BiP/GRP78, which is thought to be an ER chaperone relieving the ER stress. However, the cells expressing wild-type IRE1α significantly elevated the BiP/GRP78
expression on account of dieldrin treatment. In addition, ΔIRE1α expressing cells showed higher rate of morphological features of apoptosis than cells expressing wild-type IRE1α or mock (empty plasmid) after treatment with dieldrin. These results suggest that c-terminal kinase domain of IRE1α is a key component in the battle against ER stress and neuronal cell death.