High impact information on HSPA5

• Stable transfection of cells with antisense RNA targeted against GRP78 (pkASgrp78 cells) prevented GRP78 induction, disabled the ER stress response, sensitized cells to H2O2-induced injury, and prevented the development of tolerance to H2O2 that normally occurs with preconditioning [1].
• These results indicate that GRP78 plays an important role in the ER stress response and cytoprotection [1].
• Iodoacetamide (IDAM) is an alkylating toxicant that up-regulates expression of hsp70 (Liu, H., Lightfoot, D. L., and Stevens, J. L. (1996) J. Biol. Chem. 271, 4805-4812) and grp78 in LLC-PK1 renal epithelial cells [2].
• Prior heat shock did not protect cells from IDAM but pretreatment with trans-4,5-dihydroxy-1,2-dithiane (DTTox), thapsigargin, or tunicamycin enhanced expression of the endoplasmic reticulum (ER) chaperones GRP78 and GRP94 and rendered cells tolerant to IDAM [2].
• Cells expressing a 524-base pair antisense grp78 fragment (pkASgrp78) had a diminished capacity to up-regulate grp78 and grp94 expression after ER stress [2].

Biological context of HSPA5

• GRP78 was mapped to 1q2.10-->q2.13 and LIPE was localized to chromosome 6cen-->q1 [3].
• Endoplasmic reticulum chaperones GRP78 and calreticulin prevent oxidative stress, Ca2+ disturbances, and cell death in renal epithelial cells [2].
• Exposure of cell monolayers to tunicamycin, an inhibitor of protein glycosylation, mimicked the effect of NO2 exposure on expression of GRP-78 [4].
• Thus, the expression of grp78 antisense perturbs ER functions and activates expression of other ER stress genes accounting for the resistance to apoptosis [5].

Anatomical context of HSPA5

• The probable correspondence of P72 with the 78-kDa glucose-regulated protein (GRP78) isolated from hamster fibroblasts has been reported [6].

Associations of HSPA5 with chemical compounds

• Increased expression of GRP-78 was also detected when cell monolayers were exposed to the calcium ionophore A 23187, to 2-deoxyglucose, or to glucose-free medium, which are also known to cause perturbations in protein glycosylation [4].
• Liver CYP2E1 and the endoplasmic reticulum stress signals glucose-regulated protein 78 (GRP78), caspase 12, and sterol regulatory element binding protein-1c (SREBP-1c) were each activated in pigs fed folate-deficient or ethanol diets singly or in combination [7].
• The molecular response to reductive stress in LLC-PK1 renal epithelial cells: coordinate transcriptional regulation of gadd153 and grp78 genes by thiols [8].
• Nuclear run-on assays demonstrated that DTT activated both grp78 and gadd153 genes transcriptionally [8].

Analytical, diagnostic and therapeutic context of HSPA5

• Western blot revealed the induction of GRP78, GRP94, and protein disulfide isomerase at wk 3 and 4 [9].
• Assignment of GRP78 gene to swine chromosome 1q2.12-->q2.13 by fluorescent in situ hybridization [10].

References