Mechanism of cellular uptake of a ruthenium polypyridyl complex

作者: Cindy A. Puckett , Jacqueline K. Barton

DOI: 10.1021/BI800856T

关键词: BiophysicsBiochemistryOligomycinRutheniumMembrane potentialHeLaInternalizationDeoxyglucoseValinomycinChemistryOrganic cation transport proteins

摘要: Transition metal complexes provide a promising avenue for the design of therapeutic and diagnostic agents, but limited understanding their cellular uptake is roadblock to effective application. Here, we examine mechanism entry luminescent ruthenium(II) polypyridyl complex, Ru(DIP)2dppz2+ (where DIP = 4,7-diphenyl-1,10-phenanthroline dppz dipyridophenazine), into HeLa cells, with extent measured by flow cytometry. No diminution observed under metabolic inhibition deoxyglucose oligomycin, indicating an energy-independent mode entry. The presence organic cation transporter inhibitors also does not significantly alter uptake. However, internalization sensitive membrane potential. Uptake decreases when cells are depolarized high potassium buffer increases hyperpolarized valinomycin. These results support passive diffusion cell.

参考文章(25)
J.D. Bleil, M.S. Bretscher, Transferrin receptor and its recycling in HeLa cells. The EMBO Journal. ,vol. 1, pp. 351- 355 ,(1982) , 10.1002/J.1460-2075.1982.TB01173.X
S Davis, M J Weiss, J R Wong, T J Lampidis, L B Chen, Mitochondrial and plasma membrane potentials cause unusual accumulation and retention of rhodamine 123 by human breast adenocarcinoma-derived MCF-7 cells. Journal of Biological Chemistry. ,vol. 260, pp. 13844- 13850 ,(1985) , 10.1016/S0021-9258(17)38802-6
Stanley Barban, Henry O. Schulze, The effects of 2-deoxyglucose on the growth and metabolism of cultured human cells. Journal of Biological Chemistry. ,vol. 236, pp. 1887- 1890 ,(1961) , 10.1016/S0021-9258(18)64100-6
Cindy A. Puckett, Jacqueline K. Barton, Methods to Explore Cellular Uptake of Ruthenium Complexes Journal of the American Chemical Society. ,vol. 129, pp. 46- 47 ,(2007) , 10.1021/JA0677564
B. P. Sullivan, D. J. Salmon, T. J. Meyer, Mixed phosphine 2,2'-bipyridine complexes of ruthenium Inorganic Chemistry. ,vol. 10, pp. 3334- 3341 ,(1978) , 10.1021/IC50190A006
B. Ehrenberg, V. Montana, M.D. Wei, J.P. Wuskell, L.M. Loew, Membrane potential can be determined in individual cells from the nernstian distribution of cationic dyes. Biophysical Journal. ,vol. 53, pp. 785- 794 ,(1988) , 10.1016/S0006-3495(88)83158-8
Leigh JK Boerner, Jeffrey M Zaleski, Metal complex-DNA interactions: from transcription inhibition to photoactivated cleavage. Current Opinion in Chemical Biology. ,vol. 9, pp. 135- 144 ,(2005) , 10.1016/J.CBPA.2005.02.010
Christian G. Hartinger, Stefanie Zorbas-Seifried, Michael A. Jakupec, Bernd Kynast, Haralabos Zorbas, Bernhard K. Keppler, From bench to bedside – preclinical and early clinical development of the anticancer agent indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019 or FFC14A) Journal of Inorganic Biochemistry. ,vol. 100, pp. 891- 904 ,(2006) , 10.1016/J.JINORGBIO.2006.02.013
Hermann Koepsell, Katrin Lips, Christopher Volk, Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharmaceutical Research. ,vol. 24, pp. 1227- 1251 ,(2007) , 10.1007/S11095-007-9254-Z