Grp78 is essential for 11-deoxy-16,16-dimethyl PGE2-mediated cytoprotection in renal epithelial cells
| Autor: | Jianjun Shen, Serrine S. Lau, Jing Dong, James L. Stevens, Terrence J. Monks, Zhe Jia, Maria D. Person, Sean C. Hensley |
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| Rok vydání: | 2004 |
| Předmět: |
Programmed cell death
Physiology Gene Expression Apoptosis Biology Protein Serine-Threonine Kinases p38 Mitogen-Activated Protein Kinases Dinoprostone Cell Line Iodoacetamide Kidney Tubules Proximal chemistry.chemical_compound medicine Animals Humans Electrophoresis Gel Two-Dimensional RNA Antisense Phosphorylation Endoplasmic Reticulum Chaperone BiP Heat-Shock Proteins Cell Death Intracellular Signaling Peptides and Proteins Epithelial Cells Glutathione Hydrogen Peroxide Cytoprotection Molecular biology Epithelium Hydroquinones medicine.anatomical_structure Eicosanoid Biochemistry chemistry Cell culture Toxicity Kidney Diseases Molecular Chaperones |
| Zdroj: | American journal of physiology. Renal physiology. 287(6) |
| ISSN: | 1931-857X |
| Popis: | 11-Deoxy-16,16-dimethyl PGE2(DDM-PGE2) protects renal proximal tubule epithelial cells (LLC-PK1) against the toxicity induced by 2,3,5- tris(glutathion- S-yl)hydroquinone (TGHQ), a potent nephrotoxic and nephrocarcinogenic metabolite of hydroquinone. We have now determined the ability of DDM-PGE2to protect against other renal toxicants and report that DDM-PGE2only protects against oncotic cell death, induced by H2O2, iodoacetamide, and TGHQ, but not against apoptotic cell death induced by cisplatin, mercuric chloride, or tumor necrosis factor-α. DDM-PGE2-mediated cytoprotection is associated with the upregulation of at least five proteins, including the major endoplasmic reticulum (ER) chaperone glucose-regulated protein 78 (Grp78). To elucidate the role of Grp78 in oncotic cell death, we used LLC-PK1cells in which induction of grp78 expression was disrupted by stable expression of an antisense grp78 RNA (pkASgrp78). As anticipated, DDM-PGE2failed to induce Grp78 in pkASgrp78 cells, with a concomitant inability to provide cytoprotection. In contrast, DDM-PGE2induced Grp78 and afforded cytoprotection against H2O2, iodoacetamide, and TGHQ in empty vector transfected cells (pkNEO). These data suggest that Grp78 plays an essential role in DDM-PGE2-mediated cytoprotection. Moreover, TGHQ-induced p38 MAPK activation is disrupted under conditions of a compromised ER stress response in pkASgrp78 cells, which likely contributes to the loss of cytoprotection. Finally, using two-dimensional gel electrophoresis coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy, we found that DDM-PGE2induced several proteins in pkNEO cells, but not in pkASgrp78 cells, including retinol-binding protein, myosin light chain, and heat shock protein 27. The findings suggest that additional proteins may act in concert with Grp78 during DDM-PGE2-mediated cytoprotection against oncotic cell death. |
| Databáze: | OpenAIRE |
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