Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P33527 (ABCC1)
 1,164 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aging modifies a number of functional and phenotypic parameters of cells from the immune system. In this study, the activities of two members of the superfamily of ATP-binding cassette (ABC) transport proteins, ABCB1 and ABCC (measured by rhodamine 123 efflux and Fluo-3 efflux respectively), were compared in murine bone marrow cells and thymocytes of young (3-4 weeks old), adult (2-3 months old) and old (18 months old) mice. ABCB1 activity was shown to be age regulated in murine bone marrow mononuclear cells and thymocytes. In the bone marrow, the increased amount of cells with ABCB1 activity observed in old mice was restricted to the c-kit(-)Sca-1(+) and c-kit(+)Sca-1(+) subpopulations. Only a small percentage of c-kit(+) cells in the thymus had ABCB1 activity, and this subpopulation increased with age. In the thymus, old age augmented this activity in the CD4(-) CD8(-) double-negative cells and in the CD4(+) and CD8(+) single-positive populations. The activity of another ABC transporter, the ABCC-related activity, was also modified by age in the bone marrow. However, the age-related increase was observed in the subpopulations were ABCB1 was not modified, namely the non-progenitor population (c-kit(-)Sca-1(-)cells) and c-kit(+)Sca-1(-) cells. Nearly, all thymocytes expressed the ABCC1 molecule in an active form and aging did not affect this pattern. This study demonstrates an independent upregulation of ABCB1 and ABCC activities during the aging process. The increases were observed in different subsets of cells but followed a developmentally regulated pattern. The functions played by these transporters and alterations in aging are discussed.
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PMID:Independent regulation of ABCB1 and ABCC activities in thymocytes and bone marrow mononuclear cells during aging. 1763 1

The marine plathyhelminth Macrostomum lignano was recently isolated from Adriatic shore sediments where it experiences a wide variety of environmental challenges, ranging from hypoxia and reoxygenation, feeding on toxic algae, to exposure to anthropogenic contaminants. As multidrug resistance transporters constitute the first line of defense against toxins and toxicants we have studied the presence of such transporters in M. lignano in living animals by applying optical methods and pharmacological inhibitors that had been developed for mammalian cells. Application of the MDR1 inhibitor Verapamil or of the MRP1 inhibitors MK571 or Probenecid increased the intracellular fluorescence of the reporter dyes Fura-2 am, Calcein am, Fluo-3 am in the worms, but did not affect their staining with the dyes Rhodamine B, CMFDA or Ageladine A. The marine sponge alkaloid Ageladine A remained intracellularly trapped for several days in the worms, suggesting that it does not serve as substrate of multidrug resistance exporters. In addition, Ageladine A did not affect multidrug resistance-associated protein (MRP)-mediated dye export from M. lignano or the MRP1-mediated glutathione (GSH) export from cultured rat brain astrocytes. The data obtained demonstrate that life-imaging is a useful tool to address physiological drug export from intact marine transparent flatworms by using multiphoton scanning microscopy.
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PMID:Reporter dyes demonstrate functional expression of multidrug resistance proteins in the marine flatworm Macrostomum lignano: the sponge-derived dye Ageladine A is not a substrate of these transporters. 2413 11