Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00369 (ROS)
 19,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inside-out patches from ROS plasma membranes contain the basic enzymes of the phototransduction cascade. Similar to a native photoreceptor cell, such patches are capable of responding to light, the effect of which suppresses the cGMP-activated current. Photoresponses are observed only in the presence of GTP, whereas ATP essentially accelerates the current recovery to a dark level. Photoresponses are also observed in the presence of 8BrcGMP. Phosphodiesterase (PDE) hydrolyzes 8BrcGMP two orders of magnitude slower than cGMP, so the light inhibition of the 8BrcGMP-induced current cannot be accounted for by PDE activation. It seems that activity of cGMP-gated channels depends not only on cGMP concentration, but is additionally controlled by some other regulatory mechanisms.
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PMID:Photosensitivity of 8BrcGMP-induced conductance in ROS-excised patches. 128 91

A Ca(2+)-pumping ATPase activity is present in bovine retinal rod outer segment purified disks. The ATPase has a high Ca2+ affinity (KM = 25 microM). Low Ca2+ (n-microM) concentrations stimulate an ATP-dependent Ca2+ uptake and the ATP hydrolysis in the absence of exogenous Mg2+. Electrophoretic analysis of disk proteins after treatment with (gamma-32P)ATP shows the existence of the enzyme-phosphate acid-stable, hydroxylamine-sensitive intermediate complex of molecular mass of about 135 kDa. The results would indicate the presence of an inwardly directed Ca(2+)-ATPase pump acting on the disk membrane, that could be involved in the regulation of cytosolic free Ca2+ levels inside ROS.
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PMID:Calcium adenosinetriphosphatase of bovine retinal rod outer segment disks. 129 13

ATP released from damaged cells or by controlled secretion could be an important factor in the formation or remodeling of bone. In a variety of other tissues ATP has been shown to control cellular processes by acting on P2-purinoceptors and activating the calcium signaling pathway. Here we demonstrate for the first time that extracellular ATP increases the intracellular free calcium [Ca2+]i concentration in normal human osteoblasts and in SaOS-2 cells, a human osteosarcoma-derived cell line, but not in ROS 17/2.8 cells. The ATP-induced increase in [Ca2+]i was dose dependent, and the concentrations of ATP required were similar to those reported to regulate cellular functions in other cell types. Although ATP is metabolized rapidly by bone cells, the effects on [Ca2+]i appeared to be mediated directly by ATP rather than one of its metabolites. Adenosine 3-thiotriphosphate, a nonhydrolyzable analog of ATP, induced similar changes in [Ca2+]i. This indicates that P2-purinoceptors are present on osteoblast-like cells and that extracellular ATP from various sources might be an important factor in the regulation of osteoblast functions.
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PMID:Evidence for P2-purinoceptors on human osteoblast-like cells. 161 57

Light, in the presence of ATP, has been reported to stimulate cGMP binding to a 58 kDa protein in ROS (rod outer segments, Fesenko and Krapivinsky, 1986b, Photobiochem. Photobiophys. 13 345-58). This apparent light-related redistribution of ROS cGMP has been suggested to eliminate any requirement for phosphodiesterase-promoted hydrolysis of cGMP in the mechanism subserving phototransduction. Using conditions identical to those previously reported, this effect of light and ATP was examined further by characterizing the metabolic products that arise and the nucleotides that become liganded. The increased binding of radiolabeled guanine nucleotide upon illumination of ROS in the presence of ATP was confirmed, but the species of guanine nucleotide that were stimulated to bind under these conditions were identified as [32P]GDP and [32P]GTP rather than [32P]cGMP. The precautions to prevent enzymic hydrolysis of cGMP, which included conducting the reactions at 0 degrees and the addition of 3-isobutyl-l-methylxanthine (250 microM) to the reaction mixture did not prevent about a 20-fold increase in the rate of phosphodiesterase-catalyzed hydrolysis of radiolabeled cGMP by light when ATP was also present. This stimulation of phosphodiesterase activity is undoubtedly related to transphosphorylation by exogenous ATP of endogenous GMP and GDP involving catalytic actions of guanylate kinase and nucleoside diphosphate kinase in isolated ROS. These enzymes can also serve to generate [32P]GDP and [32P]GTP, which subsequently bind to ROS components. Such a mechanism involving ATP as phosphoryl donor was supported by observing that an analog of ATP (beta,gamma-methyleneadenosine 5'-triphosphate), which cannot serve as a phosphoryl donor, did not increase radiolabeled guanine nucleotide binding. Although several ROS proteins can form filter-retainable complexes with GDP and GTP, the properties of the 58 kDa protein found to be photoaffinity labeled with radioactive guanine nucleotide are most characteristic of those attributable to tubulin. The previous report that illumination in the presence of ATP stimulates the binding of cGMP to ROS components finds no support from the data obtained in the present studies.
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PMID:Non-identity of cGMP as the guanine nucleotide stimulated to bind to ROS by light and ATP. 254 44

Activation of the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] receptor-hormone complex was studied in-vitro using cytosolic preparations of rat osteogenic sarcoma cell ROS 17/2-8 and a DNA-cellulose assay. We found that salt was required for extraction of the unoccupied receptor indicating its possible nuclear localization. The 1,25(OH)2D3 receptor underwent an activation process similar to other steroid hormones which could be stimulated by heat and salt. At physiological ionic strength 100% of the complexes were, however, activated at 2 degrees C, indicating that the activation process is not absolutely temperature dependent. In contrast to other steroid hormones, 30-50% of the complexes were in an activated state in the absence of heat and salt moreover, alkaline phosphatase and ammonium sulphate had no effect on activation. Activation was also stimulated by ATP and ATP plus 8BrcAMP indicating the possible role of phosphorylation in the activation process; however, further work is required to clarify this point.
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PMID:Activation of the 1,25-dihydroxyvitamin D3 receptor in cultured rat osteogenic sarcoma cells. 299 3

An abundant, light-modified protein of Mr approximately equal to 51 kD, homologous to a previously described protein (termed 48K, arrestin, or S-antigen) of bovine retina, was identified and characterized in rod photoreceptors of the toad (Bufo marinus). Isolated, intact retinas were incubated in darkness, or irradiated under physiological conditions [dark-adapted (DA) and light-adapted (LA) retinas]. Using polyclonal antibodies raised in rabbit against purified toad 48K, and post-embedding immunoelectron microscopy (second antibody conjugated with 5 nm gold particles), we examined the localization of 48K in DA vs. LA rods. Physiological incubations and early fixation steps were carried out in the presence vs. absence of ATP (40 microM), a substance thought to support the activity of 48K in vivo. The distribution of 48K in rods was analyzed by quantitating the density of gold label within subcellular compartments. In DA rods, labeling was highest in the myoid region of the inner segment. Light adaptation increased 48K immunoreactivity within the outer segment, and decreased labeling within calycal processes. Labeling in outer segments of LA rods was maximal in the basal region. Treatment with ATP both amplified the light-dependent increase in basal OS labeling, and augmented the nonuniformity of basal vs. apical labeling in LA ROS. Morphometric analysis of labeling density over the length of DA vs. LA ROS indicated an approximately equal to 1.5-fold net increase in 48K label in LA ROS. By comparison, biochemical analysis of 48K level indicated an approximately equal to 1.8-fold increase in 48K in LA preparations. Together, the biochemical and immunocytochemical data indicate that the relative amount of 48K is increased in LA ROS, not just its immunoreactivity. The data are consistent with a selective movement of 48K, a cytoplasmic ROS protein, into ROS during LA.
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PMID:Immunolocalization of 48K in rod photoreceptors. Light and ATP increase OS labeling. 313 99

Endogenous nucleotide levels of isolated intact ROS were analyzed by high pressure liquid chromatography. Intact bovine ROS showed a total nucleotide concentration of 1.0 mM, ATP and GTP being the major components (0.1-0.2 mol per mol of rhodopsin). When intact ROS resuspended in sucrose-ficoll medium were diluted in a Ringer-Krebs bicarbonate, the nucleotide ratios were markedly changed, but the total concentration remained unchanged. The concentration of cyclic nucleotides (cAMP and cGMP) was markedly enhanced when ROS were placed in Ringer buffer, whereas ATP and GTP concentration was reduced. Total nucleotide concentration is 100% higher in intact than in leaky plasma membrane ROS. Upon illumination, no change was observed in the nucleotide levels of ROS in sucrose-ficoll medium. However ATP, GTP and cAMP levels were reduced when ROS in Ringer medium were exposed to light while cGMP concentration showed no change. Relevance of relative nucleotide content and ionic concentration to the transduction phenomenon in photoreceptor is discussed.
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PMID:Nucleotide content of isolated bovine rod outer segments. 630 22

1 alpha,25-Dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) has been shown to increase cytosolic calcium and inositol triphosphate levels in rat osteosarcoma cells (ROS 17/2.8) and to increase nuclear calcium in these cells. To determine the mechanism(s) of 1 alpha,25-(OH)2D3-induced changes in nuclear calcium, the effect of the hormone on phospholipid metabolism in isolated osteoblast nuclei was assessed. 1 alpha,25(OH)2D3, 20 nM, increased inositol triphosphate levels in the nuclei after 5 min of treatment. The biologically inactive epimer, 1 beta,25-(OH)2D3, had no significant effect on inositol triphosphate levels. ATP, 1 mM, also increased inositol triphosphate levels in the isolated nuclei after 5 min. 1 alpha,25-(OH)2D3, 20 nM, increased calcium in the isolated nuclei in the presence but not in the absence of extranuclear calcium within 5 min. Nuclear calcium was also increased within 5 min by ATP, 1 mM, and inositol triphosphate, 1 mM. The effect of ATP on nuclear calcium was not additive with 1 alpha,25-(OH)2D3, suggesting that these two agents increase nuclear calcium in these osteoblast-like cells by similar mechanisms. In summary, 1 alpha,25-(OH)2D3 and ATP rapidly increase inositol triphosphate levels in nuclei isolated from ROS 17/2.8 cells. The hormone, the nucleotide, and the inositol phospholipid increase nuclear calcium. Thus, the 1 alpha,25-(OH)2D3 and ATP effects on nuclear calcium may be mediated by changes in phospholipid metabolism in the nuclei of these osteoblast-like cells.
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PMID:1 alpha,25-Dihydroxyvitamin D3 rapidly alters phospholipid metabolism in the nuclear envelope of osteoblasts. 764 19

Kinesin superfamily proteins (KIFs) are probable motors in vesicular and non-vesicular transport along microtubular tracks. Since a variety of KIFs have been recently identified in the motile flagella of Chlamydomonas, we sought to ascertain whether KIFs are also associated with the connecting cilia of vertebrate rod photoreceptors. As the only structural link between the rod inner segment and the photosensitive rod outer segment, the connecting cilium is thought to be the channel through which all material passes into and out of the outer segment from the rod cell body. We have performed immunological tests on isolated sunfish rod inner-outer segments (RIS-ROS) using two antibodies that recognize the conserved motor domain of numerous KIFs (anti-LAGSE, a peptide antibody, and anti-Klp1 head, generated against the N terminus of Chlamydomonas Klp1) as well as an antibody specific to a neuronal KIF, KIF3A. On immunoblots of RIS-ROS, LAGSE antibody detected a prominent band at approximately 117 kDa, which is likely to be kinesin heavy chain, and Klp1 head antibody detected a single band at approximately 170 kDa; KIF3A antibody detected a polypeptide at approximately 85 kDa which co-migrated with mammalian KIF3A and displayed ATP-dependent release from rod cytoskeletons. Immunofluorescence localizations with anti-LAGSE and anti-Klp1 head antibodies detected epitopes in the axoneme and ellipsoid, and immunoelectron microscopy with the LAGSE antibody showed that the connecting cilium region was particularly antigenic. Immunofluorescence with anti-KIF3A showed prominent labelling of the connecting cilium and the area surrounding its basal body; the outer segment axoneme and parts of the inner segment coincident with microtubules were also labelled. We propose that these putative kinesin superfamily proteins may be involved in the translocation of material between the rod inner and outer segments.
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PMID:Localization of kinesin superfamily proteins to the connecting cilium of fish photoreceptors. 871 80

In rod and cone photoreceptor cells, activation of particulate guanylate cyclase (retGC1) is mediated by a Ca2+-binding protein termed GCAP1, that detects changes in [Ca2+]free. In this study, we show that N-acylated GCAP1 restored Ca2+ sensitivity of native and recombinant photoreceptor retGC1. ATP increased the affinity of retGC1 for GCAP1 and accelerated catalysis. Using peptides derived from the GCAP1 sequence, we found that at least three regions, encompassing the N-terminus, the EF-1 motif, and the EF-3 motif, were likely involved in the interaction with retGC1. Mutation of 2Gly to Ala (GCAP1-G2A), which abolished myristoylation and a 25 amino acid truncation at the N-terminus (delta25-GCAP1) reduced retGC1-stimulating activity dramatically, while deletion of 10 amino acids (delta10-GCAP1) reduced the specific activity by only approximately 60% and modified the Ca2+ sensitivity. At 10(-6) M [Ca2+]free, in conditions that inactivated native GCAP1, retGC1 showed significant activity in the presence of delta10-GCAP1. Native and all three mutant forms of GCAP1 had similar affinities for Ca2+ as demonstrated by gel filtration and the changes in tryptophan fluorescence. All mutants bound to ROS membranes in a Ca2+-independent manner, except delta25-GCAP1, which was mostly soluble. These findings suggest that the N-terminal region is important in tethering of GCAP1 to the ROS membranes.
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PMID:Functional reconstitution of photoreceptor guanylate cyclase with native and mutant forms of guanylate cyclase-activating protein 1. 910 25


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