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10.1091/mbc.e04-12-1096

http://scihub22266oqcxt.onion/10.1091/mbc.e04-12-1096
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suck abstract from ncbi


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pmid16251362
      Mol+Biol+Cell 2006 ; 17 (1 ): 498-510
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  • Visualization of vacuolar acidification-induced transcription of genes of pathogens inside macrophages #MMPMID16251362
  • Martin-Orozco N ; Touret N ; Zaharik ML ; Park E ; Kopelman R ; Miller S ; Finlay BB ; Gros P ; Grinstein S
  • Mol Biol Cell 2006[Jan]; 17 (1 ): 498-510 PMID16251362 show ga
  • The objective of these studies was to analyze the role of the ionic environment of phagosomal vacuoles in the control of pathogens by macrophages. Digital imaging and flow cytometry were used to follow the induction of the phoP promoter of Salmonella enterica Typhimurium within live macrophages. Manipulating the Mg2+ concentration within the Salmonella-containing vacuole (SCV) was without effect on the early induction of PhoPQ. Moreover, direct measurement of [Mg2+] within the SCV using nanosensor particles showed that, during this initial period of phoP activation, the concentration of the divalent cation is rapidly regulated and stabilizes around 1 mm. Extrusion of other divalent cations via the Nramp1 efflux pump was similarly ruled out as an important contributor to the activation of the regulon. By contrast, induction of PhoP was greatly attenuated when the pH gradient across the SCV membrane was dissipated. A second, more modest pH-independent component of PhoP induction was unmasked by inhibition of the vacuolar proton pump. This second component was eliminated by pretreatment of cells with IFNgamma, even though the cytokine augmented the overall PhoP response. These findings demonstrate the existence of at least three separate activators of phoP transcription: resting and IFNgamma-stimulated pH-sensitive components, plus a pH-independent component.
  • |*Gene Expression Regulation, Bacterial/drug effects [MESH]
  • |*Transcription, Genetic/drug effects [MESH]
  • |Acids/pharmacology [MESH]
  • |Animals [MESH]
  • |Bacterial Proteins/genetics/metabolism [MESH]
  • |Cation Transport Proteins/deficiency/genetics/metabolism [MESH]
  • |Cations, Divalent/chemistry [MESH]
  • |Cell Line [MESH]
  • |Hydrogen-Ion Concentration [MESH]
  • |Interferon-gamma/pharmacology [MESH]
  • |Macrophages/*cytology/drug effects/*microbiology [MESH]
  • |Magnesium/chemistry/metabolism/pharmacology [MESH]
  • |Mice [MESH]
  • |Mice, Knockout [MESH]
  • |Recombinant Proteins/genetics/metabolism [MESH]
  • |Salmonella Infections/microbiology [MESH]
  • |Salmonella typhimurium/drug effects/*genetics [MESH]
  • |Time Factors [MESH]


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