Tags

Type your tag names separated by a space and hit enter

Brefeldin A, thapsigargin, and AIF4- stimulate the accumulation of GRP78 mRNA in a cycloheximide dependent manner, whilst induction by hypoxia is independent of protein synthesis.
J Cell Physiol. 1992 Sep; 152(3):545-52.JC

Abstract

The glucose regulated proteins (GRPs) are major structural components of the endoplasmic reticulum (ER) and are involved in the import, folding, and processing of ER proteins. Expression of the glucose regulated proteins (GRP78 and GRP94) is greatly increased after cells are exposed to stress agents (including A23187 and tunicamycin) which inhibit ER function. Here, we demonstrate that three novel inhibitors of ER function, thapsigargin (which inhibits the ER Ca(2+)-ATPase), brefeldin A (an inhibitor of vesicle transport between the ER and Golgi) and AIF4-, (which inhibits trimeric G-proteins), can increase the expression of both GRP78 and 94. The common characteristic shared by activators of GRP expression is that they disrupt some function of the ER. The increased levels of GRPs may be a response to the accumulation of aberrant proteins in the ER or they may be increased in response to structural/functional damage to the ER. The increased accumulation of GRP78 mRNA after exposure of cells to either thapsigargin, brefeldin A, AIF4-, A23187, or tunicamycin can be blocked by pre-incubation in cycloheximide. In contrast, accumulation of GRPs after exposure to hypoxia was independent of cycloheximide. In addition, the protein kinase inhibitor genistein blocked the thapsigargin induced accumulation of GRP78 mRNA, whereas the protein phosphatase inhibitor okadaic acid caused increased accumulation of GRP78 mRNA. The data indicates that there are at least 2 mechanisms for induced expression of GRPs, one of which involves a phosphorylation step and requires new protein synthesis (e.g., thapsigargin, A23187) and one which is independent of both these steps (hypoxia).

Authors+Show Affiliations

Joint Center for Radiation Therapy, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1506413

Citation

Price, B D., et al. "Brefeldin A, Thapsigargin, and AIF4- Stimulate the Accumulation of GRP78 mRNA in a Cycloheximide Dependent Manner, Whilst Induction By Hypoxia Is Independent of Protein Synthesis." Journal of Cellular Physiology, vol. 152, no. 3, 1992, pp. 545-52.
Price BD, Mannheim-Rodman LA, Calderwood SK. Brefeldin A, thapsigargin, and AIF4- stimulate the accumulation of GRP78 mRNA in a cycloheximide dependent manner, whilst induction by hypoxia is independent of protein synthesis. J Cell Physiol. 1992;152(3):545-52.
Price, B. D., Mannheim-Rodman, L. A., & Calderwood, S. K. (1992). Brefeldin A, thapsigargin, and AIF4- stimulate the accumulation of GRP78 mRNA in a cycloheximide dependent manner, whilst induction by hypoxia is independent of protein synthesis. Journal of Cellular Physiology, 152(3), 545-52.
Price BD, Mannheim-Rodman LA, Calderwood SK. Brefeldin A, Thapsigargin, and AIF4- Stimulate the Accumulation of GRP78 mRNA in a Cycloheximide Dependent Manner, Whilst Induction By Hypoxia Is Independent of Protein Synthesis. J Cell Physiol. 1992;152(3):545-52. PubMed PMID: 1506413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brefeldin A, thapsigargin, and AIF4- stimulate the accumulation of GRP78 mRNA in a cycloheximide dependent manner, whilst induction by hypoxia is independent of protein synthesis. AU - Price,B D, AU - Mannheim-Rodman,L A, AU - Calderwood,S K, PY - 1992/9/1/pubmed PY - 1992/9/1/medline PY - 1992/9/1/entrez SP - 545 EP - 52 JF - Journal of cellular physiology JO - J Cell Physiol VL - 152 IS - 3 N2 - The glucose regulated proteins (GRPs) are major structural components of the endoplasmic reticulum (ER) and are involved in the import, folding, and processing of ER proteins. Expression of the glucose regulated proteins (GRP78 and GRP94) is greatly increased after cells are exposed to stress agents (including A23187 and tunicamycin) which inhibit ER function. Here, we demonstrate that three novel inhibitors of ER function, thapsigargin (which inhibits the ER Ca(2+)-ATPase), brefeldin A (an inhibitor of vesicle transport between the ER and Golgi) and AIF4-, (which inhibits trimeric G-proteins), can increase the expression of both GRP78 and 94. The common characteristic shared by activators of GRP expression is that they disrupt some function of the ER. The increased levels of GRPs may be a response to the accumulation of aberrant proteins in the ER or they may be increased in response to structural/functional damage to the ER. The increased accumulation of GRP78 mRNA after exposure of cells to either thapsigargin, brefeldin A, AIF4-, A23187, or tunicamycin can be blocked by pre-incubation in cycloheximide. In contrast, accumulation of GRPs after exposure to hypoxia was independent of cycloheximide. In addition, the protein kinase inhibitor genistein blocked the thapsigargin induced accumulation of GRP78 mRNA, whereas the protein phosphatase inhibitor okadaic acid caused increased accumulation of GRP78 mRNA. The data indicates that there are at least 2 mechanisms for induced expression of GRPs, one of which involves a phosphorylation step and requires new protein synthesis (e.g., thapsigargin, A23187) and one which is independent of both these steps (hypoxia). SN - 0021-9541 UR - https://www.unboundmedicine.com/medline/citation/1506413/Brefeldin_A_thapsigargin_and_AIF4__stimulate_the_accumulation_of_GRP78_mRNA_in_a_cycloheximide_dependent_manner_whilst_induction_by_hypoxia_is_independent_of_protein_synthesis_ L2 - https://doi.org/10.1002/jcp.1041520314 DB - PRIME DP - Unbound Medicine ER -