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Vacuolar ATPase (vacuolar + atpase)
Selected AbstractsNeuron-specific expression of atp6v0c2 in zebrafish CNSDEVELOPMENTAL DYNAMICS, Issue 9 2010Ah-Young Chung Abstract Vacuolar ATPase (V-ATPase) is a multi-subunit enzyme that plays an important role in the acidification of a variety of intracellular compartments. ATP6V0C is subunit c of the V0 domain that forms the proteolipid pore of the enzyme. In the present study, we investigated the neuron-specific expression of atp6v0c2, a novel isoform of the V-ATPase c-subunit, during the development of the zebrafish CNS. Zebrafish atp6v0c2 was isolated from a genome-wide analysis of the zebrafish mibta52b mutant designed to identify genes differentially regulated by Notch signaling. Whole-mount in situ hybridization revealed that atp6v0c2 is expressed in a subset of CNS neurons beginning several hours after the emergence of post-mitotic neurons. The ATP6V0C2 protein is co-localized with the presynaptic vesicle marker, SV2, suggesting that it is involved in neurotransmitter storage and/or secretion in neurons. In addition, the loss-of-function experiment suggests that ATP6V0C2 is involved in the control of neuronal excitability. Developmental Dynamics 239:2501,2508, 2010. © 2010 Wiley-Liss, Inc. [source] A Vacuolar ATPase Inhibitor, FR167356, Prevents Bone Resorption in Ovariectomized Rats With High Potency and Specificity: Potential for Clinical Application,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2005Kazuaki Niikura MS Abstract FR167356, a novel inhibitor of vacuolar ATPase, has high potency against osteoclast V-ATPase and low potency against lysosomal V-ATPase. FR167356 is the first compound of this nature to be tested. It has the potential to be useful for clinical application. Introduction: It has been suggested that the key issue regarding the therapeutic usefulness of V-ATPase inhibitors is their selectivity. Materials and Methods: In in vitro and in vivo studies, we compared FR167356 with other vacuolar ATPase (V-ATPase) inhibitors, bafilomycin A1 and SB242784. H+ transport by various membrane vesicles was assayed by measuring uptake of acridine orange. Inhibitory activity against in vitro bone resorption was examined by measuring the Ca2+ release from cultured calvariae. In vivo, hypercalcemia was induced by retinoic acid in thyroparathyroidectomized-ovariectomized rats, and the effect on serum Ca2+ level was assessed. Ovariectomized rats were treated with FR167356 or SB242784. One week after surgery, free deoxypyridinoline levels in 24-h urine samples, which were collected from 6 h after administration of FR167356, were measured by ELISA. After 4 weeks of treatment, plasma biochemical parameters were analyzed. BMD of the distal femur metaphysis was measured with pQCT. Histomorphometric analysis of the proximal tibias was performed. Blood gases of rats treated with FR167356 were measured with a blood gas analyzer for estimating the effect of FR167356 on in vivo function of renal V-ATPase. Results: FR167356, which is distinctly different from other V-ATPase inhibitors, has a high potency against osteoclast V-ATPase and low potency against lysosomal V-ATPase. Similarly, FR167356 inhibited bone resorption in vitro when stimulated by PTH, IL-1, and IL-6. FR167356 reduced retinoic acid-induced hypercalcemia in thyroparathyroidectomized-ovariectomized rats in a dose-dependent manner. Moreover, FR167356 was shown to restore BMD of ovariectomized rats caused by the inhibition of bone resorption. Ovariectomized rats treated with FR167356 did not show adverse symptoms, whereas SB242784 caused a decrease in body weight gain and significant changes in two plasma biochemical parameters. Interestingly, FR167356 treatment did not affect blood acid-base balance; however, FR167356 inhibited renal V-ATPase with a similar potency as for osteoclast V-ATPase inhibition. Conclusion: Comparison of FR167356 with SB242784 implies that the characteristics of FR167356 may be more appropriate for clinical application as a V-ATPase inhibitor. [source] 1141424444 Detection of a2V-ATPase in T regulatory cells of women with recurrent spontaneous abortions or implantation failuresAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2006EI Ntrivalas Problem:, T regulatory cells (Tregs) have recently been shown to play a critical role in maternal tolerance to the fetus. Tregs are decreased in women with recurrent miscarriages. a2V-ATPase (previously referred to as Regeneration and Tolerance Factor) is expressed in activated lymphocytes and plays a role in immune regulation. The aim of this study was to investigate the expression of a2V-ATPase on CD4+/CD25bright Tregs. Method of Study:, Whole blood from women with RSA or implantation failures was reacted with anti-CD4 and anti-CD25 mAbs for the identification of CD4+/CD25bright and CD4+/CD25neg T cells by flow cytometric analysis. Subsequently, these two T-cell populations were analyzed for the expression of a2V-ATPase using PE-conjugated 2C1 mAb (specific for the membrane portion of a2V-ATPase). These two cell populations were also analyzed for the expression of CD71, CD62L, CD45RO and CD58 (Treg markers). Results:, a2V-ATPase was more highly expressed on CD4+/CD25bright Tregs (22.8 ± 16.4%) than on CD4+/CD25neg T cells (2.4 ± 3.8%) in women with RSA (P < 0.0001). Additionally, a2V-ATPase was more highly expressed on CD4+/CD25bright Tregs (18.0 ± 18.2%) than on CD4+/CD25neg T cells (1.5 ± 1.4%) in women with implantation failures (P < 0.0001). a2V-ATPase expression also coincided with the expression of CD71, CD62L, CD45RO and CD58 in Tregs, as opposed to the conventional CD4+/CD25neg T cells. Conclusions:, The expression of a2V-ATPase in Tregs of women with RSA or implantation failures is a novel finding and suggests that this vacuolar ATPase plays an important role in suppression. a2V-ATPase may be a unique molecule in the identification of Tregs among peripheral blood lymphocytes and may also explain the tolerogenic activity of these cells. [source] | ||||||||||