Sulová Zdena, Orlický Jozef, Fiala Roderik, Dovinová Ima, Uhrík Branislav, Seres Mário, Gibalová Lenka, Breier Albert
Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlárska 5, 833 34 Bratislava, Slovakia.
Biochem Biophys Res Commun. 2005 Sep 30;335(3):777-84. doi: 10.1016/j.bbrc.2005.07.144.
L1210/VCR cell line (R) was obtained by adaptation of the L1210 mouse leukaemia cells (S) to vincristine and showed P-glycoprotein (P-gp) mediated multidrug resistance (MDR). R cells were observed to be more sensitive to high external calcium as parental S. More pronounced calcium uptake was observed for R cells. Moreover, differences in intracellular calcium cell localization between S and R cells were found ultrastructurally following a calcium precipitating cytochemical method. In S cells, calcium precipitates were found to be localized predominantly along the cell surface coat and within mitochondria delineating the cristae. In R cells, precipitates were also found inside nuclei, at the border of heterochromatin clumps, and scattered within the cytoplasm. High extracellular calcium did not influence the P-gp mediated extrusion of calcein/AM as P-gp substrate. These results indicate that calcium enters and consequently damages the MDR cells to a higher extent than parental cells.
L1210/VCR细胞系（R）是通过将L1210小鼠白血病细胞（S）适应长春新碱而获得的，表现出P-糖蛋白（P-gp）介导的多药耐药性（MDR）。观察到R细胞比亲代S细胞对高细胞外钙更敏感。R细胞的钙摄取更明显。此外，采用钙沉淀细胞化学方法在超微结构上发现S细胞和R细胞之间细胞内钙的定位存在差异。在S细胞中，发现钙沉淀主要位于细胞表面被膜以及线粒体嵴内。在R细胞中，沉淀也存在于细胞核内、异染色质团块边界处，并散布于细胞质中。高细胞外钙并不影响作为P-gp底物的钙黄绿素/AM的P-gp介导的外排。这些结果表明，与亲代细胞相比，钙进入并因此对多药耐药细胞造成更大程度的损伤。
