C-reactive protein (CRP) is one of the major members of the family of acute phase proteins (APP). Interest in this CRP was the result of a seminal discovery of its pattern of response to pneumococcal infection in humans. CRP has the unique property of reacting with phosphocholine-containing substances, such as pneumococcal C-polysaccharide, in the presence of Ca.
View Article and Find Full Text PDFA reduction in the number of functional β-cells is the central pathological event in diabetes. Liver and ventral pancreas differentiates simultaneously in the same general domain of cells within embryonic endoderm. In addition, the precursor cell population being bi-potential may be targeted for either pancreas or liver development.
View Article and Find Full Text PDFThe enzymatic cleavage of the nicotinamide-glycosidic bond on nicotinamide adenine dinucleotide (NAD(+)) has been proposed to go through an oxocarbenium ion-like transition state. Because of the instability of the ionic intermediate, there has been no structural report on such a transient reactive species. Human CD38 is an ectoenzyme that can use NAD(+) to synthesize two calcium-mobilizing molecules.
View Article and Find Full Text PDFHuman CD38 is a multifunctional protein involved in diverse functions. As an enzyme, it is responsible for the synthesis of two Ca2+ messengers, cADPR and NAADP; as an antigen, it is involved in regulating cell adhesion, differentiation, and proliferation. Besides, CD38 is a marker of progression of HIV-1 infection and a negative prognostic marker of B-CLL.
View Article and Find Full Text PDFADP-ribosyl cyclase catalyzes the elimination of nicotinamide from NAD and cyclization to cADPR, a known second messenger in cellular calcium signaling pathways. We have determined to 2.0 A resolution the structure of Aplysia cyclase with ribose-5-phosphate bound covalently at C3' and with the base exchange substrate (BES), pyridylcarbinol, bound to the active site.
View Article and Find Full Text PDFGranulocytic differentiation of human HL-60 cells can be induced by retinoic acid and is accompanied by a massive expression of CD38, a multi-functional enzyme responsible for metabolizing cyclic ADP-ribose (cADPR), a Ca(2+) messenger. Immunofluorescence staining showed that CD38 was expressed not only on the surface of intact HL-60 cells but also intracellularly, which was revealed after permeabilization with Triton. Concomitant with CD38 expression was the accumulation of cADPR, and both time courses preceded the onset of differentiation, suggesting a causal role for CD38.
View Article and Find Full Text PDFCD38 is a multifunctional enzyme involved in metabolizing two Ca(2+) messengers, cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP). When incubated with NAD, CD38 predominantly hydrolyzes it to ADP-ribose (NAD glycohydrolase), but a trace amount of cADPR is also produced through cyclization of the substrate. Site-directed mutagenesis was used to investigate the amino acid important for controlling the hydrolysis and cyclization reactions.
View Article and Find Full Text PDFRecent studies have provided evidence for a role of cyclic ADP-ribose (cADPR) in the regulation of intracellular calcium in smooth muscles of the intestine, blood vessels and airways. We investigated the presence and subcellular localization of ADP-ribosyl cyclase, the enzyme that catalyzes the conversion of beta-NAD(+) to cADPR, and cADPR hydrolase, the enzyme that degrades cADPR to ADPR, in tracheal smooth muscle (TSM). Sucrose density fractionation of TSM crude membranes provided evidence that ADP-ribosyl cyclase and cADPR hydrolase activities were associated with a fraction enriched in 5'-nucleotidase activity, a plasma membrane marker enzyme, but not in a fraction enriched in either sarcoplasmic endoplasmic reticulum calcium ATPase or ryanodine receptor channels, both sarcoplasmic reticulum markers.
View Article and Find Full Text PDFCD38 is a ubiquitous protein originally identified as a lymphocyte antigen and recently also found to be a multifunctional enzyme participating in the synthesis and metabolism of two Ca(2+) messengers, cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate. It is homologous to Aplysia ADP-ribosyl cyclase, where the crystal structure has been determined. Residues of CD38 corresponding to those at the active site of the Aplysia cyclase were mutagenized.
View Article and Find Full Text PDFADP-ribosyl cyclase synthesizes two Ca(2+) messengers by cyclizing NAD to produce cyclic ADP-ribose and exchanging nicotinic acid with the nicotinamide group of NADP to produce nicotinic acid adenine dinucleotide phosphate. Recombinant Aplysia cyclase was expressed in yeast and co-crystallized with a substrate, nicotinamide. x-ray crystallography showed that the nicotinamide was bound in a pocket formed in part by a conserved segment and was near the central cleft of the cyclase.
View Article and Find Full Text PDFMol Cell Biochem
March 1999
ADP-ribosyl cyclase and CD38 are multi-functional enzymes involved in calcium signaling. Both can cyclize NAD and its guanine analog, NGD, at two different sites of the purine ring, N1 and N7, respectively, to produce cyclic ADP-ribose (cADPR) and cyclic GDP-ribose, a fluorescent but inactive analog. Both enzymes can also catalyze the exchange of the nicotinamide group of NADP with nicotinic acid, producing yet another potent activator of Ca2+ mobilization, nicotinic acid adenine dinucleotide phosphate (NAADP).
View Article and Find Full Text PDFADP-ribosyl cyclase is a multi-functional enzyme that catalyzes the formation of two Ca2+ signaling molecules, cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP). X-ray crystallography of three different crystal forms shows that it is a non-covalent dimer. Chemical cross-linking and dynamic light scattering were used in this study to determine if the cyclase is also a non-covalent dimer in solution.
View Article and Find Full Text PDFHuman recombinant CD38 catalyzes the formation of both cyclic ADP-ribose and ADP-ribose products from NAD+ and hydrolyzes cyclic ADP-ribose to ADP-ribose. The corresponding GDP products are formed from NGD+. The enzyme was characterized by substrate and inhibition kinetics, exchange studies, rapid-quench reactions, and stopped-flow-fluorescence spectroscopy to establish the reaction mechanism and energetics for individual steps.
View Article and Find Full Text PDFProtein Expr Purif
October 1997
Cyclic ADP-ribose (cADPR), a Ca2+ mobilizing cyclic nucleotide derived from NAD+, is rapidly emerging as an endogenous modulator of Ca2(+)-induced Ca2+ release mechanisms in various cellular systems. ADP ribosyl cyclase, first isolated from the marine invertebrate Aplysia californica, cyclizes NAD+ to cADPR. In this study we have utilized the methylotrophic yeast Pichia pastoris to express high levels of this enzyme.
View Article and Find Full Text PDFAnesth Analg
November 1995
This study was designed to compare the effectiveness of antagonism of mivacurium blockade with either neostigmine, edrophonium, or spontaneous recovery. Thirty ASA physical status I or II patients provided informed consent and were randomized to one of the following groups: Group 1, placebo saline; Group 2, edrophonium (1 mg/kg); and Group 3, neostigmine (70 micrograms/kg) (n = 10/group). All studied patients had anesthesia induced with propofol and maintained with propofol/N2O/fentanyl.
View Article and Find Full Text PDFInteractions between beta-lactam antibiotics, particularly acylaminopenicillins, and vecuronium, a widely used muscle relaxant, leading to prolonged neuromuscular blockade have been reported in studies of experimental animals and in a few clinical case reports. In the clinical reports, however, confounding factors always existed. A clinical trial to evaluate interactions between vecuronium and cefoxitin or piperacillin was conducted.
View Article and Find Full Text PDFObjective: To quantify the effect of an induction dose of midazolam on median nerve somatosensory evoked potentials.
Methods: We studied 10 patients undergoing lumbar spine surgery. After an induction dose of intravenous midazolam was given, MNEPs were collected for ten minutes.
Biol Trace Elem Res
September 1992
A comparison of two methods of selenium application, banding and foliar spray, of sodium selenite (Na2SeO3) on total glycoalkaloid (TGA) and nitrate nitrogen (NO3-N) was studied during each of two consecutive years. The levels of application used were 0.0, 1.
View Article and Find Full Text PDFA patient is described in whom migration of an endotracheal tube into the right main bronchus was suspected when end-tidal carbon dioxide suddenly decreased from 28 to 22 mm Hg. Acute changes with migration of the endotracheal tube into the main bronchus were also studied in an animal experimental model. End-tidal carbon dioxide decreased and tracheal (inflation) pressure increased, with no change in tidal volume.
View Article and Find Full Text PDFA potentially serious problem is inherent in the current design of the mass spectrometer multiplex system. In spite of the filter on the sampling tube, foreign material can be aspirated into this tube, causing malfunction of the system. Prevention of this problem is discussed, and precautions are given.
View Article and Find Full Text PDFAnesthetic agents are sometimes added to the wrong vaporizer on an anesthesia machine. As a result, the vaporizer may deliver a mixture of anesthetic agents at concentrations inappropriate for use on a patient. However, untoward clinical complications related to vaporizers can be prevented with a time-shared mass spectrometer.
View Article and Find Full Text PDF