Topic
DIDS
About: DIDS is a research topic. Over the lifetime, 1728 publications have been published within this topic receiving 60459 citations. The topic is also known as: 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid & ABC inhibitor 2.
Papers published on a yearly basis
Papers
Journal Article•
TL;DR: Measurement of pH in tissue has shown that the microenvironment in tumors is generally more acidic than in normal tissues, and acid conditions in tumors might allow the development of new and relatively specific types of therapy which are directed against mechanisms which regulate pHi under acid conditions.
Abstract: Measurement of pH in tissue has shown that the microenvironment in tumors is generally more acidic than in normal tissues. Major mechanisms which lead to tumor acidity probably include the production of lactic acid and hydrolysis of ATP in hypoxic regions of tumors. Further reduction in pH may be achieved in some tumors by administration of glucose (+/- insulin) and by drugs such as hydralazine which modify the relative blood flow to tumors and normal tissues. Cells have evolved mechanisms for regulating their intracellular pH. The amiloride-sensitive Na+/H+ antiport and the DIDS-sensitive Na+-dependent HCO3-/Cl- exchanger appear to be the major mechanisms for regulating pHi under conditions of acid loading, although additional mechanisms may contribute to acid extrusion. Mitogen-induced initiation of proliferation in some cells is preceded by cytoplasmic alkalinization, usually triggered by stimulation of Na+/H+ exchange; proliferation of other cells can be induced without prior alkalinization. Mutant cells which lack Na+/H+ exchange activity have reduced or absent ability to generate solid tumors; a plausible explanation is the failure of such mutant cells to withstand acidic conditions that are generated during tumor growth. Studies in tissue culture have demonstrated that the combination of hypoxia and acid pHe is toxic to mammalian cells, whereas short exposures to either factor alone are not very toxic. This interaction may contribute to cell death and necrosis in solid tumors. Acidic pH may influence the outcome of tumor therapy. There are rather small effects of pHe on the response of cells to ionizing radiation but acute exposure to acid pHe causes a marked increase in response to hyperthermia; this effect is decreased in cells that are adapted to low pHe. Acidity may have varying effects on the response of cells to conventional anticancer drugs. Ionophores such as nigericin or CCCP cause acid loading of cells in culture and are toxic only at low pHc; this toxicity is enhanced by agents such as amiloride or DIDS which impair mechanisms involved in regulation of pHi. It is suggested that acid conditions in tumors might allow the development of new and relatively specific types of therapy which are directed against mechanisms which regulate pHi under acid conditions.
1,755 citations
TL;DR: The mechanisms underlying the release of O 2 ⨪ from mitochondria into cytosol are elucidated, and the role of outer membrane voltage-dependent anion channels (VDACs) in this process is assessed, noting the importance of these processes for modulating cell signaling pathways in these compartments.
727 citations
TL;DR: (3H)DIDS was used as a convalent label for membrane sites involved in anion permeability resulting in almost complete inhibition of anion exchange and because of the linear relationship of binding to inhibition and the unique architecture of the site, it is suggested that the (3H)'s-binding site is the substrate binding site of the anion transport system.
Abstract: (3H)DIDS (4,4′-diisothiocyano-2,2′-ditritiostilbene-disulfonate) was used as a convalent label for membrane sites involved in anion permeability. The label binds to a small, superficially located population of sites, about 300,000 per cell, resulting in almost complete inhibition of anion exchange. The relationship of biding to inhibition is linear suggesting that binding renders each site nonfunctional. In the inhibitory range less than 1% of the label is associated with lipids but at higher concentrations of DIDS, the fraction may be as high as 4%. In ghosts, however, treatment with (3H)DIDS results in extensive labeling of lipids. In cells, a protein fraction that behavens on SDS acrylamide gels as thought its molecular weight is 95,000 daltons (95K) is predominatly labeled by (3H)DIDS. The only other labeled protein is the major sialoglycoprotein which contains less than, 5% of the total bound (3H)DIDS. Because of the linear relationship of binding to inhibition and the unique architecture of the site, it is suggested that the (3H)DIDS-binding site of the 95K protein is the substrate binding site of the anion transport system. The 95K protein is asymmetrically arranged in the membrane with the sites arranged on the outer face accessible to agent in the medium. In “leaky” ghost, only a few additional binding sites can be reached from the inside of the membrane in the 95K protein, in contrast to the extensive labeling of other membrane proteins in ghosts as compared to cells.
723 citations
TL;DR: The results indicate that peroxynitrite is able to cross the erythrocyte membrane by two different mechanisms: in the anionic form through the DIDS-inhibitable anion channel, and in the protonated form by passive diffusion.
Abstract: Peroxynitrite anion (ONOO−) is a reactive species of increasingly recognized biological relevance that contributes to oxidative tissue damage At present, however, there is limited knowledge about the mechanisms of peroxynitrite diffusion through biological compartments In this work we have studied the diffusion of peroxynitrite across erythrocyte membranes In solution, peroxynitrite rapidly reacts with oxyhemoglobin to yield methemoglobin, with k2 = (104 ± 03) × 103 M−1⋅s−1 at pH 74 and 25°C Addition of peroxynitrite to intact erythrocytes caused oxidation of intracellular oxyhemoglobin to methemoglobin Oxidation yields in red blood cells at pH 70 were approximately 40% of those obtained in solution, which results mostly from competition of other cytosolic components for peroxynitrite Indeed, rather small differences were observed between oxidation yields in lysates compared with intact erythrocytes, in particular at acidic and neutral pH values, indicating that membrane was not precluding peroxynitrite diffusion Incubation of erythrocytes at pH 70 with 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS), a specific inhibitor of anion exchange, resulted in up to 50% inhibition of oxyhemoglobin oxidation by peroxynitrite More protection by DIDS was achieved at alkaline pH, while no effect was observed at pH 55, where 95% of peroxynitrite is in the acidic form, ONOOH (pKa = 68) In addition, peroxynitrite caused nitration of intracellular hemoglobin, in a process that was enhanced in thiol-depleted erythrocytes Our results indicate that peroxynitrite is able to cross the erythrocyte membrane by two different mechanisms: in the anionic form through the DIDS-inhibitable anion channel, and in the protonated form by passive diffusion
417 citations
TL;DR: The results suggest possible genetic heterogeneity of this mechanism of mycobacterial killing associated with P2Z-mediated pore formation and ATP-mediated bacterial killing was independent of reactive nitrogen and oxygen intermediates and of actinomycin D or cycloheximide inhibition.
406 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2024 | 3 |
| 2023 | 6 |
| 2022 | 17 |
| 2021 | 7 |
| 2020 | 14 |
| 2019 | 14 |