Author
Loris G. Baggetto
Bio: Loris G. Baggetto is an academic researcher from Centre national de la recherche scientifique. The author has contributed to research in topics: P-glycoprotein & Transfection. The author has an hindex of 13, co-authored 26 publications receiving 800 citations.
Papers
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TL;DR: These and other regulatory aberrations in tumor cells appear to be reflections of a complex set of non-random phenotypic changes, initiated by expression of oncogenes.
284 citations
TL;DR: Evidence is provided that caveolin‐1 regulates p‐gp function through the phosphorylation state of caveolin•1 in endothelial cells from the blood–brain barrier in rat brain endothelial cell line (RBE4).
Abstract: p-glycoprotein (p-gp) is an ATP-binding cassette transporter and its overexpression is responsible for the acquisition of the multidrug resistance phenotype in human tumors. p-gp is localized at the blood-brain barrier and is involved in brain cytoprotection. Our previous work used immunoprecipitation to show that caveolin-1 can interact with p-gp. In this study, we provide evidence that caveolin-1 regulates p-gp transport activity in a rat brain endothelial cell line (RBE4). Down-regulation of caveolin-1 by siRNA reduced the interaction between p-gp and caveolin-1, followed by a decrease in [3H]-Taxol and [3H]-Vinblastine accumulation in RBE4 cells. The latter result showed that down-regulation of caveolin-1 enhanced p-gp transport activity. RBE4 cells were also transfected with Sarcoma in order to modulate caveolin-1 phosphorylation. Overexpression of Sarcoma, a protein tyrosine kinase, stimulated caveolin-1 phosphorylation and increased both [3H]-Taxol and [3H]-Vinblastine accumulation as well as Hoechst 33342 accumulation. Transfection of caveolin-1 inhibits p-gp transport activity. Conversely, transfection of the mutant cavY14F decreased the p-gp/caveolin-1 interaction and reduced accumulation of the two p-gp substrates. Thus, our data show that caveolin-1 regulates p-gp function through the phosphorylation state of caveolin-1 in endothelial cells from the blood-brain barrier.
79 citations
TL;DR: The results put forward a functional role for the tryptophan-containing sequence of P-glycoprotein NBD2 that was not detected up to now and potentially prevented or chased by ATP or ADP at millimolar concentrations.
72 citations
TL;DR: A general procedure for efficient purification of P-glycoprotein by combining solubilization with sodium dodecyl sulfate and chromatography on ceramic hydroxyapatite was developed and yielded 70% of the P- glycoprotein present in the starting plasma membranes with more than 99% purity.
58 citations
TL;DR: SDS-treated P-glycoprotein, glutamate dehydrogenase, and Lysozyme fully recovered their enzymatic activities after HAP chromatography, including lysozyme electroeluted from SDS-polyacrylamide gel electrophoresis, demonstrating that reactivation of SDS -treated protein can be achieved, provided that SDS is completely removed under mild conditions.
40 citations
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TL;DR: New data suggests that this metabolic switch within the solid tumour may provide a benefit to the tumour not by increasing glycolysis but by decreasing mitochondrial activity.
Abstract: It has been known for many years that cellular metabolism within the solid tumour is markedly different from that of the corresponding normal tissue. The transcription factor hypoxia-inducible factor 1 (HIF1) has been implicated in regulating many of the genes that are responsible for the metabolic difference. However, it remains unclear how this 'aerobic glycolysis', originally described by Otto Warburg, offers tumour cells a growth advantage. As discussed in this Perspective, new data suggests that this metabolic switch may provide a benefit to the tumour not by increasing glycolysis but by decreasing mitochondrial activity.
1,463 citations
TL;DR: This review will concentrate on the methods currently available for efficient reconstitution and solubilization of membrane proteins through the use of detergent micelles, mixed lipid/detergent micella and bicelles or liposomes and the role that lipids can play in stabilizing the proteins.
1,270 citations
TL;DR: The nature of detergent binding by the membrane from a noncooperative to a cooperative interaction already below the critical micellar concentration is considered and it is concluded that in general binding as a monolayer ring, rather than as a micelle, is the most probable mechanism.
985 citations
TL;DR: It is proposed that energy metabolism may be an alternative therapeutic target for both hypoxic (glycolytic) and oxidative tumors.
Abstract: In early studies on energy metabolism of tumor cells, it was proposed that the enhanced glycolysis was induced by a decreased oxidative phosphorylation. Since then it has been indiscriminately applied to all types of tumor cells that the ATP supply is mainly or only provided by glycolysis, without an appropriate experimental evaluation. In this review, the different genetic and biochemical mechanisms by which tumor cells achieve an enhanced glycolytic flux are analyzed. Furthermore, the proposed mechanisms that arguably lead to a decreased oxidative phosphorylation in tumor cells are discussed. As the O(2) concentration in hypoxic regions of tumors seems not to be limiting for the functioning of oxidative phosphorylation, this pathway is re-evaluated regarding oxidizable substrate utilization and its contribution to ATP supply versus glycolysis. In the tumor cell lines where the oxidative metabolism prevails over the glycolytic metabolism for ATP supply, the flux control distribution of both pathways is described. The effect of glycolytic and mitochondrial drugs on tumor energy metabolism and cellular proliferation is described and discussed. Similarly, the energy metabolic changes associated with inherent and acquired resistance to radiotherapy and chemotherapy of tumor cells, and those determined by positron emission tomography, are revised. It is proposed that energy metabolism may be an alternative therapeutic target for both hypoxic (glycolytic) and oxidative tumors.
974 citations
TL;DR: It is proposed that delineating the precise roles of these transporters in tumorigenesis and treatment response will be important for the development of more effective targeted therapies.
Abstract: Multidrug transporter proteins are best known for their contributions to chemoresistance through the efflux of anticancer drugs from cancer cells. However, a considerable body of evidence also points to their importance in cancer extending beyond drug transport to fundamental roles in tumour biology. Currently, much of the evidence for these additional roles is correlative and definitive studies are needed to confirm causality. We propose that delineating the precise roles of these transporters in tumorigenesis and treatment response will be important for the development of more effective targeted therapies.
929 citations