| Effect of thapsigargin on P-glycoprotein-negative and P-glycoprotein-positive L1210 mouse leukaemia cells. | |
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MedLine Citation:
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PMID: 21157003 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Expression of drug-transporting P-glycoprotein (P-gp, an integral protein of the plasma membrane) in neoplastic cells confers multidrug resistance and also involves alteration of cell sensitivity to inhibitors of the sarco/endoplasmic reticulum calcium pump thapsigargin (Th). Mouse leukaemia L1210 cell sublines that overexpress P-gp due to selection with vincristine (R) or stable transfection with a gene encoding human P-gp (T) were less sensitive to Th than the parental cell line (S). Th at a concentration of 0.1 μmol/l did not induce alterations in the amount of P-gp mRNA in R or T cells (S cells did not contain any measurable amount of this transcript as assessed by RT-PCR) or in the amount of calnexin (CNX) or glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in all three cell sublines. However, when using a concentration of 10 μmol/l, Th decreases the amounts of CNX, GAPDH (in S, R and T cells) and P-gp (in R and T cells) mRNAs. In contrast to R and T cells (which contain abundant P-gp), S cells did not contain any P-gp detectable by the c219 antibody on a Western blot. Th at a concentration of 0.1 μmol/l induced a reduction in the amount of P-gp present in R and T cells, particularly in isoforms with higher molecular weights (i.e., mature fully glycosylated isoforms). Similar results were observed when Th was used at a concentration of 10 μmol/l. R and T cells contained lower levels of CNX than S cells. While Th at a lower concentration did not alter the levels of CNX in S, R or T cells, a higher concentration of this substance induced a measurable decrease in the amount of CNX. S, R and T cells did not differ with respect to GAPDH content, but Th induced a reduction in the amount of this protein in all cell sublines. More pronounced results were observed when Th was applied at a concentration of 10 μmol/l comparing with a concentration of 0.1 mmol/l. These changes may be involved together with the Th efflux activity of P-gp in Th-resistance associated with the P-gp-mediated multidrug resistance of R and T cells. |
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Authors:
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Mário Sereš; Peter Ditte; Albert Breier; Zdena Sulová |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: General physiology and biophysics Volume: 29 ISSN: 0231-5882 ISO Abbreviation: Gen. Physiol. Biophys. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8400604 Medline TA: Gen Physiol Biophys Country: Slovakia |
Other Details:
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Languages: eng Pagination: 396-401 Citation Subset: IM |
Affiliation:
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Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlárska 5, 833 34 Bratislava, Slovakia. zdena.sulova@savba.sk. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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