Overexpression of GRP78/BiP in P-Glycoprotein-Positive L1210 Cells is Responsible for Altered Response of Cells to Tunicamycin as a Stressor of the Endoplasmic Reticulum
| Autor: | Zdena Sulova, Boris Lakatoš, Tomáš Kyca, Viera Bohacova, Mário Šereš, Lucia Pavlikova, Ivana Borovska, Albert Breier |
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| Rok vydání: | 2020 |
| Předmět: |
ATP Binding Cassette Transporter
Subfamily B Cell Apoptosis tunicamycin-induced ER stress Endoplasmic Reticulum Article chemistry.chemical_compound Mice Downregulation and upregulation multidrug resistance Cell Line Tumor p-glycoprotein medicine Animals Humans ATP Binding Cassette Transporter Subfamily B Member 1 lcsh:QH301-705.5 Endoplasmic Reticulum Chaperone BiP Heat-Shock Proteins P-glycoprotein Leukemia biology Chemistry Endoplasmic reticulum Tunicamycin General Medicine Transfection Cell cycle Molecular biology GRP78/BiP medicine.anatomical_structure lcsh:Biology (General) Unfolded protein response biology.protein CHOP |
| Zdroj: | Cells Cells, Vol 9, Iss 890, p 890 (2020) Volume 9 Issue 4 |
| ISSN: | 2073-4409 |
| Popis: | P-glycoprotein (P-gp, ABCB1 member of the ABC (ATP-binding cassette) transporter family) localized in leukemia cell plasma membranes is known to reduce cell sensitivity to a large but well-defined group of chemicals known as P-gp substrates. However, we found previously that P-gp-positive sublines of L1210 murine leukemia cells (R and T) but not parental P-gp-negative parental cells (S) are resistant to the endoplasmic reticulum (ER) stressor tunicamycin (an N-glycosylation inhibitor). Here, we elucidated the mechanism of tunicamycin resistance in P-gp-positive cells. We found that tunicamycin at a sublethal concentration of 0.1 µ M induced retention of the cells in the G1 phase of the cell cycle only in the P-gp negative variant of L1210 cells. P-gp-positive L1210 cell variants had higher expression of the ER stress chaperone GRP78/BiP compared to that of P-gp-negative cells, in which tunicamycin induced larger upregulation of CHOP (C/EBP homologous protein). Transfection of the sensitive P-gp-negative cells with plasmids containing GRP78/BiP antagonized tunicamycin-induced CHOP expression and reduced tunicamycin-induced arrest of cells in the G1 phase of the cell cycle. Taken together, these data suggest that the resistance of P-gp-positive cells to tunicamycin is due to increased levels of GRP78/BiP, which is overexpressed in both resistant variants of L1210 cells. |
| Databáze: | OpenAIRE |
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