1,721,266 research outputs found
Chelation of cytoplasmic Ca2+ increses plasma membrane permeability in murine macrophages
No full textCytoplasmic free Ca2+ (Ca2+i) was chelated to 10-20 nM in the macrophage cell line J774 either by incubation with quin2 acetoxymethyl ester in the absence of external Ca2+ (Di Virgilio, F., Lew, P.D., and Pozzan, T. (1984) Nature 310, 691-693) or by loading [ethyl-enebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) into the cytoplasm via reversible permeabilization of the plasma membrane with extracellular ATP (Steinberg, T.H., Newman, A.S., Swanson, J.A., and Silverstein, SS.C. (1987) J. Biol. Chem. 262, 8884-8888; Di Virgilio, F., Meyer, B.C., Greenberg, S., and Silverstein, S.C. (1988) J. Cell Biol. 106, 657-666). After removal of ATP from the incubation medium, ATP-permeabilized Ca2+i-depleted macrophages recovered a near-normal plasma membrane potential which slowly depolarized over a 2-4 h incubation at low [Ca2+]i. In both ATP-treated and quin2-loaded cells, depolarization of plasma membrane potential was paralleled by an increase in plasma membrane permeability to low molecular weight aqueous solutes such as eosin yellowish (Mr 692), ethidium bromide (Mr 394), and lucifer yellow (Mr 463). This increased plasma membrane permeability was not accompanied by release of the cytoplasmic marker lactic dehydrogenase for incubations up to 4 h and was likely a specific effect of Ca2+i depletion since it was not caused by: (i) the mere incubation of macrophages with extracellular EGTA, i.e. at near-normal [Ca2+]i; and (ii) loading into the cytoplasm of diethylenetriaminepentaacetic acid, a specific chelator of heavy metals with low affinity for Ca2+. Treatment of Ca2+i-depleted cells with direct (phorbol 12-myristate 13-acetate) or indirect (platelet-activating factor) activators of protein kinase C prevented the increase in plasma membrane permeability. Down-regulation of protein kinase C rendered Ca2+i-depleted macrophages refractory to the protective effect of phorbol 12-myristate 13-acetate. This report suggests a role for Ca2+i and possibly protein kinase C in the regulation of plasma membrane permeability to low molecular weight aqueous solutes
La reingegnerizzazione dei processi nei sistemi produttivi locali: il Fast Perfect Order
No full textEditorial overview: Purinergic P2X receptors in innate immunity and inflammation
No full textNo abstract availabl
First joint Italian-German Purine Club meeting"Progress in Purinergic Receptor Pharmacology and Function".
No full textP2X7 is a cytotoxic receptor….maybe not: implications for cancer
No full textThe tumor microenvironment is rich in extracellular ATP. This nucleotide affects both cancer and infiltrating immune cell responses by acting at P2 receptors, chiefly P2X7. ATP is then degraded to generate adenosine, a very powerful immunosuppressant. The purinergic hypothesis put forward by Geoff Burnstock prompted innovative investigation in this field and provided the intellectual framework to interpret a myriad of experimental findings. This is a short appraisal of how Geoff’s inspiration influenced cancer studies and my own investigation highlighting the key role of the P2X7 receptor
Editorial overview: Immunometabolism
No full textEnergy metabolism is a key determinant of the immune response. Classical biochemistry has precisely dissected intracellular metabolic pathways, highlighting how cells adapt to different tasks requiring increasing energy demand. However, until about two decades ago, most immunologists assumed that immune cells were a realm apart that did not comply with the general rules of metabolic control effective in all other tissues. Little to no attention was paid to the possibility that different activation or differentiation states of immune cells, whether innate or adaptive, might be associated with different metabolic pathways or that different immunostimulatory factors might promote the preferential engagement of specific metabolic pathways. Likewise, no mentions were made about 'immunometabolism' in most immunology textbooks, and even 'Tlymphocyte exhaustion' is rarely mentioned. Rather, immune cells are not much different from other lineages for their metabolic requirements: they require ATP, metabolic substrates (glucose, fatty acids, but also lactate, glutamine, and other amino acids), and the oxidizing agent (oxygen) (although at times they can adapt to a limited supply) to make ATP from
The Mechanism of Ca2+ Release Induced by N-Ethylmaleimide in Rat Liver Mitochondria
No full textThe SH-group reagent N-ethylmaleimide has become widely used as inhibitor of Pi transport in mitochondria. MalNEt decreases the ability of mitochondria to retain Ca2+ and evidence is provided that the Ca2+ efflux observed in MalNEt-treated mitochondria is not due to membrane damage. In contrast, N-ethylmaleimide-induced Ca2+ loss from mitochondria was accompanied by drastic alterations of e- flow
and membrane permeability. We aim to clarify the mechanism of N-ethylmaleimide-induced Ca2+ release. It will be shown that N-ethylmaleimide does not alter per se the inner mitochondrial membrane but its effects are rather mediated by the rise of deltapH following divalent cation uptake. Thus, it appears that the rise of deltapH, and not N-ethylmaleimide per se, is responsible for the decreased e- transfer at site II and for the increased permeability to K+ and H+
Review: Ear (extracellular ATP receptors) - A new family of plasma membrane molecules widely distributed in sensory systems
No full textAdenosine triphosphate (ATP), besides being a universal intermediate for intracellular energy transductions, is also a ubiquitous mediator of cell-to-cell communication. It is now well established that this nucleotide is involved in extracellular signalling in virtually any sensory system, the cochlea included. Adenosine triphosphate is released under several physiological and pathological conditions and its signalling is mediated by a novel family of receptors named P2 purinergic receptors. The P2 receptor family comprises two sub-families (P2Y and P2X) that are widely distributed throughout the body, and are also expressed in the inner ear. The purinergic signalling system exhibits a high degree of regulation as all cells also express plasma membrane ecto-ATPases/nucleotidases with the catalytic site exposed to the pericellular space. Activity of these enzymes rapidly curtails ATP-dependent cell stimulation. The end product of plasma membrane ecto-ATPases/nucleotidases is adenosine, ..
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