Concentrative Influx of Functionally Active Cyclic ADP-ribose in Dimethyl Sulfoxide-differentiated HL-60 Cells

Guida, Lucrezia; Franco, Luisa; Bruzzone, Santina; Sturla, Laura; Zocchi, Elena; Basile, Giovanna; Usai, Cesare; Flora, Antonio De

doi:10.1074/jbc.m314137200

Cited by 31 publications

(33 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This "topological paradox" has been addressed [138,139]. It is shown that NAD can leak out of the cell via connexin hemi-channels [140,141] and made available to the type-II CD38, while the product, cADPR, produced is transported back into the cell by nucleoside transporters present in the plasma membrane [142,143]. This pathway is depicted in Figure 5.…”

Section: Membrane Topology and Regulation Of Cd38mentioning

confidence: 99%

Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling

Lee

2011

Sci. China Life Sci.

View full text Add to dashboard Cite

The concept advanced by Berridge and colleagues that intracellular Ca 2+ -stores can be mobilized in an agonist-dependent and messenger (IP 3 )-mediated manner has put Ca 2+ -mobilization at the center stage of signal transduction mechanisms. During the late 1980s, we showed that Ca 2+ -stores can be mobilized by two other messengers unrelated to inositol trisphosphate (IP 3 ) and identified them as cyclic ADP-ribose (cADPR), a novel cyclic nucleotide from NAD, and nicotinic acid adenine dinucleotide phosphate (NAADP), a linear metabolite of NADP. Their messenger functions have now been documented in a wide range of systems spanning three biological kingdoms. Accumulated evidence indicates that the target of cADPR is the ryanodine receptor in the sarco/endoplasmic reticulum, while that of NAADP is the two pore channel in endolysosomes.As cADPR and NAADP are structurally and functionally distinct, it is remarkable that they are synthesized by the same enzyme. They are thus fraternal twin messengers. We first identified the Aplysia ADP-ribosyl cyclase as one such enzyme and, through homology, found its mammalian homolog, CD38. Gene knockout in mice confirms the important roles of CD38 in diverse physiological functions from insulin secretion, susceptibility to bacterial infection, to social behavior of mice through modulating neuronal oxytocin secretion. We have elucidated the catalytic mechanisms of the Aplysia cyclase and CD38 to atomic resolution by crystallography and site-directed mutagenesis. This article gives a historical account of the cADPR/NAADP/CD38-signaling pathway and describes current efforts in elucidating the structure and function of its components.cyclic ADP-ribose, cADPR, NAADP, nicotinic acid adenine dinucleotide phosphate, CD38, ADP-ribosyl cyclase, Calcium mobilization and signaling Citation:Lee H C. Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling. Sci China Life Sci, 2011Sci, , 54: 699 -711, doi: 10.1007 In 1983, Berridge and colleagues published a study showing that agonists, such as carbachol, can activate Ca 2+ release from non-mitochondrial Ca 2+ stores and the effect is mediated by a Ca 2+ messenger, inositol 1,4,5-trisphosphate (IP 3 ) [1]. The targeted Ca 2+ stores were later identified as the endoplasmic reticulum (ER), which has since been shown to be the major intracellular Ca 2+ stores. This seminal study ushered in the current field of Ca 2+ signaling as we know it and has made the field center stage. IP 3 is derived from a phospholipid, phosphatidyl inositol 4,5-bisphosphate, present on the cytoplasmic side of the plasma membrane. Agonist binding to its specific receptor leads to activation of phospholipase C and the hydrolysis of the phospholipid, releasing the head group that is IP 3 . The structure of IP 3 is shown in Figure 1. It has three phosphates on the inositol ring. Both the number of phosphates and the position of the phosphates are critical to the binding of IP 3 to its receptor in the ER. The space-filling model of IP 3 shown in Figu...

show abstract

Section: Membrane Topology and Regulation Of Cd38mentioning

confidence: 99%

Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling

Lee

2011

Sci. China Life Sci.

View full text Add to dashboard Cite

show abstract

“…It is difficult to envision how cADPR and NAADP can function inside the cell if they are generated by ectoenzymes. Several studies suggest that cADPR and NAADP are directly transported by CD38 or more likely by nucleotide transporters into the cytosol [10][11][12][13][14]. So far, in many cell types, responding to extracellular NAD + with an increase in [Ca 2+ ] i , conversion of NAD + to the Ca 2+ mobilizer cADPR [14][15][16][17][18] has been implicated as the principal mechanism leading to the rise in [Ca 2+ ] i .…”

Section: Introductionmentioning

confidence: 99%

Involvement of P2X receptors in the NAD+-induced rise in [Ca2+]i in human monocytes

Grahnert

Klein

Hauschildt

2009

Purinergic Signalling

View full text Add to dashboard Cite

In the present study, we show that the extracellular addition of nicotinamide adenine dinucleotide (NAD + ) induces a transient rise in [Ca 2+ ] i in human monocytes caused by an influx of extracellular calcium. The NAD + -induced Ca 2+ response was prevented by adenosine triphosphate (ATP), suggesting the involvement of ATP receptors. Of the two subtypes of ATP receptors (P2X and P2Y), the P2X receptors were considered the most likely candidates. By the use of subtype preferential agonists and antagonists, we identified P2X 1 , P2X 4 , and P2X 7 receptors being engaged in the NAD + -induced rise in [Ca 2+ ] i . Among the P2X receptor subtypes, the P2X 7 receptor is unique in facilitating the induction of nonselective pores that allow entry of ethidium upon stimulation with ATP. In monocytes, opening of P2X 7 receptor-dependent pores strongly depends on specific ionic conditions. Measuring pore formation in response to NAD + , we found that NAD + unlike ATP lacks the ability to induce this pore-forming response. Whereas as little as 100 μM ATP was sufficient to activate the nonselective pore, NAD + at concentrations up to 2 mM had no effect. Taken together, these data indicate that despite similarities in the action of extracellular NAD + and ATP there are nucleotide-specific variations. So far, common and distinct features of the two nucleotides are only beginning to be understood.

show abstract

“…The paracrine interaction between stroma and HP has been investigated in a transwell co-culture setting where human HP were cultured over confluent monolayers of murine stromal cells transfected with human CD38: NAD ϩ efflux from stromal cells through connexin 43-formed hemichannels (8) provides CD38 with its substrate for ectocellular production of cADPR; subsequent influx of the cyclic nucleotide into HP (both committed and uncommitted progenitors) induces intracellular calcium ([Ca 2ϩ ] i ) mobilization and cell proliferation (6). In a similar co-culture setting, influx of cADPR into target 3T3 fibroblasts and dimethyl sulfoxide (Me 2 SO)-differentiated HL-60 cells has been demonstrated to occur across concentrative nucleoside transporter(s) (CNT) sensitive to dipyridamole and nitrobenzylthioinosine (NBMPR) (9,10) and to induce an increase of the [Ca 2ϩ ] i and of proliferation (11). While paracrine production of cADPR by the CD38 ϩ stroma was beneficial to HP growth, the increase of [Ca 2ϩ ] i induced on stromal cells themselves by autocrinally generated cADPR proved to trigger interferon-␥ (IFN-␥) release.…”

mentioning

confidence: 99%

Concentrative Uptake of Cyclic ADP-ribose Generated by BST-1+ Stroma Stimulates Proliferation of Human Hematopoietic Progenitors

Podestà

Benvenuto

Pitto

et al. 2005

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Cyclic ADP-ribose (cADPR) is an intracellular calcium mobilizer generated from NAD؉ by the ADP-ribosyl cyclases CD38 and BST-1. cADPR, both exogenously added and paracrinally produced by a CD38؉ feeder layer, has recently been demonstrated to stimulate the in vitro proliferation of human hemopoietic progenitors (HP) and also the in vivo expansion of hemopoietic stem cells. The low density of BST-1 expression on bone marrow (BM) stromal cells and the low specific activity of the enzyme made it unclear whether cADPR generation by a BST-1 ؉ stroma could stimulate HP proliferation in the BM microenvironment. We developed and characterized two BST-1 ؉ stromal cell lines, expressing an ectocellular cyclase activity similar to that of BST-1 ؉ human mesenchymal stem cells, the precursors of BM stromal cells. Long term co-culture of cord blood-derived HP over these BST-1 ؉ feeders determined their expansion. Influx of paracrinally generated cADPR into clonogenic HP was mediated by a concentrative, nitrobenzylthioinosine-and dipyridamole-inhibitable nucleoside transporter, this providing a possible explanation to the effectiveness of the hormone-like concentrations of the cyclic nucleotide measured in the medium conditioned by BST-1 ؉ feeders. These results suggest that the BST-1-catalyzed generation of extracellular cADPR, followed by the concentrative uptake of the cyclic nucleotide by HP, may be physiologically relevant in normal hemopoiesis.The self-renewal capacity of hemopoietic progenitors (HP) 1 in the bone marrow (BM) is a fundamental process in the physiology of hemopoiesis. The role of the BM stroma in providing HP with soluble factors essential to their proliferation and differentiation is well established (1, 2). However, the nature of the signals and the mechanisms by which stromal cells regulate the behavior of HP remain largely to be defined. Particularly, it is unknown whether perturbations of the balance between growth-stimulatory and -inhibitory factors may influence the expansion and self-renewal capacity of the hemopoietic reservoir.Recently, we have demonstrated that the potent intracellular calcium mobilizer cyclic ADP-ribose (cADPR) (3, 4) features properties of a novel hemopoietic growth factor (5, 6). Coinfusion of human HP with murine stromal cells transfected with the human ectocellular ADP-ribosyl cyclase CD38 improves hemopoietic stem cells engraftment into NOD/SCID mice (7). The paracrine interaction between stroma and HP has been investigated in a transwell co-culture setting where human HP were cultured over confluent monolayers of murine stromal cells transfected with human CD38: NAD ϩ efflux from stromal cells through connexin 43-formed hemichannels (8) provides CD38 with its substrate for ectocellular production of cADPR; subsequent influx of the cyclic nucleotide into HP (both committed and uncommitted progenitors) induces intracellular calcium ([Ca 2ϩ ] i ) mobilization and cell proliferation (6). In a similar co-culture setting, influx of cADPR into target 3T3 fibroblasts and dimet...

show abstract

Concentrative Influx of Functionally Active Cyclic ADP-ribose in Dimethyl Sulfoxide-differentiated HL-60 Cells

Cited by 31 publications

References 41 publications

Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling

Cyclic ADP-ribose and NAADP: fraternal twin messengers for calcium signaling

Involvement of P2X receptors in the NAD+-induced rise in [Ca2+]i in human monocytes

Concentrative Uptake of Cyclic ADP-ribose Generated by BST-1+ Stroma Stimulates Proliferation of Human Hematopoietic Progenitors

Contact Info

Product

Resources

About