Neuronal localization of CD38 antigen in the human brain

Mizuguchi, Masashi; Otsuka, Naruhito; Sato, Mário Teruo; Ishii, Yoshifumi; Kon, Shinichiro; Yamada, Mitsunori; Nishina, Hiroshi; Katada, Toshiaki; Ikeda, Kazuhiko

doi:10.1016/0006-8993(95)00885-t

Cited by 87 publications

(56 citation statements)

References 16 publications

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“…This is the first demonstration that 3T3 cells are responsive to cADPR; although HeLa cells have been already described to express type II ryanodine receptor (36), 3T3 cells are reported not to express any known type of ryanodine receptor (36). In addition we found that repeated Ca 2ϩ loading of permeabilized 3T3 cells eventually resulted in Ca 2ϩ release from intracellular stores, 4 this strongly suggesting a Ca 2ϩ -induced Ca 2ϩ release mechanism. This fact and responsiveness of permeabilized 3T3 cells to cADPR seem to imply the occurrence in these cells of an unidentified type of cADPR receptor.…”

Section: Discussionsupporting

confidence: 60%

Expression of CD38 Increases Intracellular Calcium Concentration and Reduces Doubling Time in HeLa and 3T3 Cells

Zocchi

Daga²,

Usai

et al. 1998

Journal of Biological Chemistry

119

161

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CD38 is a bifunctional ectoenzyme, predominantly expressed on hematopoietic cells during differentiation, that catalyzes the synthesis (cyclase) and the degradation (hydrolase) of cyclic ADP-ribose (cADPR), a powerful calcium mobilizer from intracellular stores. Due to the well established role of calcium levels in the regulation of apoptosis, proliferation, and differentiation, the CD38/cADPR system seems to be a likely candidate involved in the control of these fundamental processes. CD38 is a type II transmembrane glycoprotein predominantly expressed on lymphocytes (1) but also present in a number of different cell types, including erythrocytes (2), hematopoietic progenitor cells (1), ␤-pancreatic cells (3), and cerebral (4) and cerebellar (5) neurons. Immunologically, CD38 can be defined as an "orphan receptor" since its binding by specific monoclonal antibodies directed against ectocellular epitopes elicits cellular responses in lymphocytes, including proliferation, activation, and rescue from apoptosis (6, 7). The signal transduction pathways implicated in these events are under study, but phosphorylation/dephosphorylation reactions of target kinases have been already demonstrated (6,8,9). Biochemically, CD38 is a bifunctional ectoenzyme that catalyzes the synthesis of cADPR 1 from NAD ϩ and also its hydrolysis to ADPR (2, 10). Cyclic ADPR is a potent Ca 2ϩ mobilizer from intracellular stores, in invertebrate as well as in mammalian cells (11), and its presence has been described in most mammalian tissues (12).The widespread tissue distribution of the CD38/cADPR system suggests its involvement in the control of pivotal Ca 2ϩ -controlled functions like contraction, secretion, cell proliferation/differentiation, and apoptosis. However, the topological paradox of the ectocellular production of an intracellular Ca 2ϩ mobilizer has raised questions on both the immunological and the biochemical functions of the CD38/cADPR system (13, 14). Cell death has been advocated as a means for local increase in extracellular NAD ϩ concentrations, sufficient to elicit the production of cADPR by the ectoenzyme CD38; in this respect, nanomolar concentrations of NAD ϩ have been detected in plasma (15) and cerebellar interstitial fluid (5) suggesting the theoretical possibility of an extracellular production of cADPR by CD38 "in vivo." In few selected cell systems, i.e. murine B-lymphocytes (10), rat cerebellar granule cells (5), and rat osteoclasts (16), extracellular, exogenously added cADPR was demonstrated to elicit functional responses in intact cells, but most reported effects of cADPR on cellular functions require permeabilization of target cells to ensure binding of the nucleotide to its intracellular receptor(s).Internalization of membrane-bound CD38, as observed in human Namalwa B-lymphocytes upon incubation with NAD ϩ or thiol reagents, is followed by an increase of intracellular cyclase activity (insensitive to protein synthesis inhibitors) and of intracellular cADPR concentration ([cADPR] i ) (17), suggesting that...

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Section: Discussionsupporting

confidence: 60%

Expression of CD38 Increases Intracellular Calcium Concentration and Reduces Doubling Time in HeLa and 3T3 Cells

Zocchi

Daga²,

Usai

et al. 1998

Journal of Biological Chemistry

119

161

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“…Therefore, the absence of ADP-ribosyl cyclase activity from embryonic neurons in culture may be attributable to an effect of growing the cells in tissue culture or to a developmental phenomenon. In fact, CD38 has been demonstrated immunocytochemically in the cell bodies and dendrites of neurons in the adult human cerebellum and cerebral cortex (Mizuguchi et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Synthesis of cADP-Ribose from Nicotinamide-Adenine Dinucleotide by Rat Cortical Astrocytes in Culture

et al. 1996

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cADPR is an endogenous calcium-mobilizing agent that in vertebrates is synthesized from nicotinamide-adenine dinucleotide (NAD) by bifunctional enzymes with ADP-ribosyl cyclase and cADPR hydrolase activity. ADP-ribosyl cyclase and cADPR hydrolase activity have been reported in the brain, but the cellular localization of these activities has not been determined previously. In the present study, selective culturing techniques were employed to localize ADP-ribosyl cyclase activity and cADPR hydrolase activity to astrocytes or neurons in cultures derived from rat embryonic cerebral cortex. ADP-ribosyl cyclase activity was determined by incubating cultures with 1 mM NAD in the extracellular medium for 60 min at 37°C and measuring formation of cADPR by bioassay and by HPLC. Astrocyte cultures and mixed cultures of astrocytes and neurons had mean specific activities of 0.84 Ϯ 0.06 and 0.9 Ϯ 0.18 nmol cADPR produced/mg protein/hr, respectively. No detectable ADP-ribosyl cyclase activity was found in neuron-enriched/ astrocyte-poor cultures. cADPR hydrolase activity was detectable by incubating cultures with 300 M cADPR for 60 min at 37°C and assaying loss of cADPR or accumulation of ADPR. The demonstration of extracellular ADP-ribosyl cyclase and cADPR hydrolase activities associated with astrocytes may have important implications for the role of extracellular cADPR in signal transduction and in intercellular communication in the nervous system.

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“…1 In the following years, several studies showed that CD38 expression is not limited to T cells but is widely expressed on different hematopoietic and nonhematopoietic tissues. [2][3][4][5] The strength of expression of CD38 on hematopoietic cells varies, depending on their stage of maturation and activation. It is expressed on CD34 ϩ progenitor cells, unstimulated pregerminal center B cells, germinal center B cells, activated mature lymphocytes, plasma cells, and myeloid precursors.…”

Section: Introductionmentioning

confidence: 99%

CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia

Ibrahim

Keating

Anh

et al. 2001

Blood

397

260

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CD38 is a transmembrane glycoprotein expressed on the surface of leukemic cells in a significant percentage of patients with Bcell chronic lymphocytic leukemia (B-CLL). A recent study suggested that CD38 expression has prognostic value in CLL. Peripheral blood samples from 218 patients with B-CLL were analyzed by flow cytometry for CD38 expression on CD5/19 ؉ leukemic cells. Various patient characteristics were studied including age, sex, Rai and Binet stages, splenomegaly, hepatomegaly, hemoglobin (Hgb) level, ␤-2 microglobulin (␤2M) level in the serum, number of nodal sites involved with disease, and length of survival. The Kaplan-Meier method was used to construct survival curves, and the log-rank statistic was used to compare these curves. CD38 was expressed in 20% or more of leukemic cells in 43% of the patients. Patients with high CD38 expression (20% or more) had significantly shorter survival times (P ‫؍‬ .00005). Multivariate analyses showed that CD38 expression is an important prognostic factor associated with high incidence of lymph node involvement (P ‫؍‬ .004), lower hemoglobin level (P ‫؍‬ .001), hepatomegaly (P ‫؍‬ .05), and high ␤2M level (P ‫؍‬ .00005).

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Neuronal localization of CD38 antigen in the human brain

Cited by 87 publications

References 16 publications

Expression of CD38 Increases Intracellular Calcium Concentration and Reduces Doubling Time in HeLa and 3T3 Cells

Expression of CD38 Increases Intracellular Calcium Concentration and Reduces Doubling Time in HeLa and 3T3 Cells

Extracellular Synthesis of cADP-Ribose from Nicotinamide-Adenine Dinucleotide by Rat Cortical Astrocytes in Culture

CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia

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