Activity of the multidrug transporter results in alkalinization of the cytosol: measurement of cytosolic pH by microinjection of a pH-sensitive dye.
AuthorsThiebaut F, Currier SJ, Whitaker J, Haugland RP, Gottesman MM, Pastan I, Willingham MC
JournalJ Histochem Cytochem
PubMed ID1692055
'Multidrug-resistant cells contain a plasma membrane efflux pump, the multidrug transporter, which actively expels certain hydrophobic drugs from the cytosol to the cell exterior. These drugs are usually positively charged at physiological pH. Because one might predict that this efflux of positively charged molecules might deplete the cytosol of protons, ... More
A novel role for carbonic anhydrase: cytoplasmic pH gradient dissipation in mouse small intestinal enterocytes.
AuthorsStewart AK, Boyd CA, Vaughan-Jones RD
JournalJ Physiol
PubMed ID10066935
'1. The spatial and temporal distribution of intracellular H+ ions in response to activation of a proton-coupled dipeptide transporter localized at the apical pole of mouse small intestinal isolated enterocytes was investigated using intracellular carboxy-SNARF-1 fluorescence in combination with whole-cell microspectrofluorimetry or confocal microscopy. 2. In Hepes-buffered Tyrode solution, application ... More
Nuclear pH gradient in mammalian cells revealed by laser microspectrofluorimetry.
AuthorsSeksek O, Bolard J
JournalJ Cell Sci
PubMed ID8834810
Intracellular pH has been measured by laser microspectrofluorimetry, using the pH-sensitive dyes SNARF-1, SNARF-calcein and SNARF-1-dextran. By this technique it was possible to accurately determine pH in volumes as small as 0.5 x 0.5 x 1 microns 3. The probes were loaded into the cells either by diffusion of their ... More
Tamoxifen inhibits acidification in cells independent of the estrogen receptor.
AuthorsAltan N, Chen Y, Schindler M, Simon SM
JournalProc Natl Acad Sci U S A
PubMed ID10200279
Tamoxifen has been reported to have numerous physiological effects that are independent of the estrogen receptor, including sensitization of resistant tumor cells to many chemotherapeutic agents. Drug-resistant cells sequester weak base chemotherapeutics in acidic organelles away from their sites of action in the cytosol and nucleus. This work reports that ... More
Defective acidification in human breast tumor cells and implications for chemotherapy.
AuthorsAltan N, Chen Y, Schindler M, Simon SM
JournalJ Exp Med
PubMed ID9584137
Multidrug resistance (MDR) is a significant problem in the treatment of cancer. Chemotherapeutic drugs distribute through the cyto- and nucleoplasm of drug-sensitive cells but are excluded from the nucleus in drug-resistant cells, concentrating in cytoplasmic organelles. Weak base chemotherapeutic drugs (e.g., anthracyclines and vinca alkaloids) should concentrate in acidic organelles. ... More
Intramolecular interactions mediate pH regulation of connexin43 channels.
AuthorsMorley GE, Taffet SM, Delmar M
JournalBiophys J
PubMed ID8785285
We have previously proposed that acidification-induced regulation of the cardiac gap junction protein connexin43 (Cx43) may be modeled as a particle-receptor interaction between two separate domains of Cx43: the carboxyl terminal (acting as a particle), and a region including histidine 95 (acting as a receptor). Accordingly, intracellular acidification would lead ... More
Determination of pH by microfluorometry: intracellular and interstitial pH regulation in developing early-stage fish embryos (Danio rerio).
AuthorsMölich A, Heisler N
JournalJ Exp Biol
PubMed ID16244172
Microfluorometric techniques were applied in vivo for continuous monitoring of specific acid-base parameters in zebrafish (Danio rerio) embryos during early stages of ontogeny. Dextran-coupled pH-sensitive single-excitation/dual-emission dye SNARF-1 was pressure-injected into individual cells or the interstitial space of 16- to 256-cell embryos, and pH was continuously recorded during subsequent development ... More