Metabolism of cyclic ADP-ribose: Zinc is an endogenous modulator of the cyclase/NAD glycohydrolase ratio of a CD38-like enzyme from human seminal fluid

Zielinska, Weronika; Barata, Hosana; Chini, Eduardo N.

doi:10.1016/j.lfs.2003.08.033

Cited by 33 publications

(30 citation statements)

References 21 publications

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“…7.2 ( Figure 1C) and was significantly inhibited by incubation with nicotinamide and dithiothreitol and was stimulated by Zn (an effect blocked by EDTA) ( Figure 1D). These results indicate that the ADP-ribosyl cyclase in T. gondii has features similar to the well-characterized mammalian ADP-ribosyl cyclase CD38 [30][31][32]. As this assay is highly sensitive for cADPR, these results indicate the presence of cyclase and hydrolase enzymes that control the production and turnover of cADPR in T. gondii.…”

Section: Evidence That T Gondii Contains An Endogenous Cadpr Pathwaysupporting

confidence: 52%

“…Extracts of T. gondii are capable of synthesizing cADPR from NAD and to degrade it through hydrolase activity. The inhibition profile of T. gondii cADPR cyclase suggests that the T. gondii cyclase has pharmacological features similar to those of the well-characterized mammalian cyclase CD38 [30][31][32]. Furthermore, T. gondii microsomes that were loaded with 45 Ca 2+ in vitro released calcium in response to cADPR.…”

Section: Discussionmentioning

confidence: 81%

“…The synthesis of cADPR by T. gondii extracts was verified by HPLC anion-exchange chromatography using an AG MP-1 (BioRad Laboratories, Hercules, CA, U.S.A.) column eluted with a nonlinear gradient of trifluoroacetic acid as described previously [30,32]. The nucleotides were detected by UV absorption at 254 nm.…”

Section: Hplc Analysis Of Nucleotidesmentioning

confidence: 99%

“…The nucleotides were detected by UV absorption at 254 nm. The authenticity of the cADPR produced was confirmed by co-elution with standard compounds and by the sea-urchin egg bioassay as described previously [30,32].…”

Section: Hplc Analysis Of Nucleotidesmentioning

confidence: 99%

“…cADPR was synthesized by Aplysia ADP-ribosyl cyclase, using homogenized Aplysia ovotestes as described previously [30,32]. The reaction was stopped by acetone precipitation as described above for the synthesis of cADPR.…”

Section: Synthesis Of Standard Nucleotidesmentioning

confidence: 99%

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Evidence that the cADPR signalling pathway controls calcium-mediated microneme secretion in Toxoplasma gondii

Chini

Nagamune

Wetzel

et al. 2005

Biochemical Journal

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The protozoan parasite Toxoplasma gondii relies on calciummediated exocytosis to secrete adhesins on to its surface where they can engage host cell receptors. Increases in intracellular calcium occur in response to Ins(1,4,5)P 3 and caffeine, an agonist of ryanodine-responsive calcium-release channels. We examined lysates and microsomes of T. gondii and detected evidence of cADPR (cyclic ADP ribose) cyclase and hydrolase activities, the two enzymes that control the second messenger cADPR, which causes calcium release from RyR (ryanodine receptor). We also detected endogenous levels of cADPR in extracts of T. gondii. Furthermore, T. gondii microsomes that were loaded with 45 Ca 2+ released calcium when treated with cADPR, and the RyR antagonists 8-bromo-cADPR and Ruthenium Red blocked this response. Although T. gondii microsomes also responded to Ins(1,4,5)P 3 , the inhibition profiles of these calcium-release channels were mutually exclusive. The RyR antagonists 8-bromocADPR and dantrolene inhibited protein secretion and motility in live parasites. These results indicate that RyR calcium-release channels that respond to the second-messenger cADPR play an important role in regulating intracellular Ca 2+ , and hence host cell invasion, in protozoan parasites.

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Section: Evidence That T Gondii Contains An Endogenous Cadpr Pathwaysupporting

confidence: 52%

Section: Discussionmentioning

confidence: 81%

Section: Hplc Analysis Of Nucleotidesmentioning

confidence: 99%

Section: Hplc Analysis Of Nucleotidesmentioning

confidence: 99%

Section: Synthesis Of Standard Nucleotidesmentioning

confidence: 99%

See 3 more Smart Citations

Evidence that the cADPR signalling pathway controls calcium-mediated microneme secretion in Toxoplasma gondii

Chini

Nagamune

Wetzel

et al. 2005

Biochemical Journal

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Small‐molecule reductants inhibit multicatalytic activity of AA‐NADase from Agkistrodon acutus venom by reducing the disulfide‐bonds and Cu(II) of enzyme

Zhang

et al. 2009

Biopolymers

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AA-NADase from Agkistrodon acutus venom is a unique multicatalytic enzyme with both NADase and AT(D)Pase activities. Among all identified NADases, only AA-NADase contains Cu(II) and has disulfide-bond linkages between two peptide chains. The effects of the reduction of the disulfide-bonds and Cu(II) in AA-NADase by small-molecule reductants on its NADase and ADPase activities have been investigated by polyacrylamide gel electrophoresis, high performance liquid chromatography, electron paramagnetic resonance spectroscopy and isothermal titration calorimetry. The results show that AA-NADase has six disulfide-bonds and fifteen free cysteine residues. L-ascorbate inhibits AA-NADase on both NADase and ADPase activities through the reduction of Cu(II) in AA-NADase to Cu(I), while other reductants, dithiothreitol, glutathione and tris(2-carboxyethyl)phosphine inhibit both NADase and ADPase activities through the reduction of Cu(II) to Cu(I) and the cleavage of disulfide-bonds in AA-NADase. Apo-AA-NADase can recover its NADase and ADPase activities in the presence of 1 mM Zn(II). However, apo-AA-NADase does not recover any NADase or ADPase activity in the presence of 1 mM Zn(II) and 2 mM TCEP. The multicatalytic activity relies on both disulfide-bonds and Cu(II), while Cu(I) can not activate the enzyme activities. AA-NADase is probably only active as a dimer. The inhibition curves for both ADPase and NADase activities by each reductant share a similar trend, suggesting both ADPase and NADase activities probably occur at the same site. In addition, we also find that glutathione and L-ascorbate are endogenous inhibitors to the multicatalytic activity of AA-NADase.

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Lipopolysaccharide Induces CD38 Expression and Solubilization in J774 Macrophage Cells

Lee

Song

Yoo

et al. 2012

Molecules and Cells

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*CD38, an ADP ribosyl cyclase, is a 45 kDa type II transmembrane protein having a short N-terminal cytoplasmic domain and a long C-terminal extracellular domain, expressed on the surface of various cells including macrophages, lymphocytes, and pancreatic β cells. It is known to be involved in cell adhesion, signal transduction and calcium signaling. In addition to its transmembrane form, CD38 is detectable in biological fluids in soluble forms. The mechanism by which CD38 is solubilized from the plasma membrane is not yet clarified. In this study, we found that lipopolysaccharide (LPS) induced CD38 upregulation and its extracellular release in J774 macrophage cells. Furthermore, it also increased CD38 expression at the mRNA level by activating the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway. However, LPS decreased the levels of CD38 in the plasma membrane by releasing CD38 into the culture supernatant. LPS-induced CD38 release was blocked by the metalloproteinase-9 inhibitor indicating that MMP-9 solubilizes CD38. In conclusion, the present findings demonstrate a potential mechanism by which C38 is solubilized from the plasma membrane.

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Metabolism of cyclic ADP-ribose: Zinc is an endogenous modulator of the cyclase/NAD glycohydrolase ratio of a CD38-like enzyme from human seminal fluid

Cited by 33 publications

References 21 publications

Evidence that the cADPR signalling pathway controls calcium-mediated microneme secretion in Toxoplasma gondii

Evidence that the cADPR signalling pathway controls calcium-mediated microneme secretion in Toxoplasma gondii

Small‐molecule reductants inhibit multicatalytic activity of AA‐NADase from Agkistrodon acutus venom by reducing the disulfide‐bonds and Cu(II) of enzyme

Lipopolysaccharide Induces CD38 Expression and Solubilization in J774 Macrophage Cells

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