A self-restricted CD38-connexin 43 cross-talk affects NAD+ and cyclic ADP-ribose metabolism and regulates intracellular calcium in 3T3 fibroblasts
| Autor: | Santina Bruzzone, Angela Bisso, Luisa Franco, Elena Zocchi, Antonio De Flora, Lucrezia Guida, Cesare Usai, Paola Contini |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
chemistry.chemical_element
Calcium CD38 Biology Biochemistry Cyclic ADP-ribose Calcium in biology chemistry.chemical_compound Mice NAD+ Nucleosidase Antigens CD hemic and lymphatic diseases Animals Phosphorylation ADP-ribosyl Cyclase Molecular Biology Protein kinase C Protein Kinase C DNA Primers Adenosine Diphosphate Ribose Cyclic ADP-Ribose Membrane Glycoproteins Base Sequence Cell Biology 3T3 Cells Fibroblasts NAD ADP-ribosyl Cyclase 1 Antigens Differentiation Cell biology Enzyme Activation Glycerol-3-phosphate dehydrogenase chemistry Connexin 43 NAD+ kinase Intracellular |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0021-9258 |
| Popis: | Connexin 43 (Cx43) hexameric hemichannels, recently demonstrated to mediate NAD(+) transport, functionally interact in the plasma membrane of several cells with the ectoenzyme CD38 that converts NAD(+) to the universal calcium mobilizer cyclic ADP-ribose (cADPR). Here we demonstrate that functional uncoupling between CD38 and Cx43 in CD38-transfected 3T3 murine fibroblasts is paralleled by decreased [Ca(2+)](i) levels as a result of reduced intracellular conversion of NAD(+) to cADPR. A sharp inverse correlation emerged between [Ca(2+)](i) levels and NAD(+) transport (measured as influx into cells and as efflux therefrom), both in the CD38(+) cells (high [Ca(2+)](i), low transport) and in the CD38(-) fibroblasts (low [Ca(2+)](i), high transport). These differences were correlated with distinctive extents of Cx43 phosphorylation in the two cell populations, a lower phosphorylation with high NAD(+) transport (CD38(-) cells) and vice versa (CD38(+) cells). Conversion of NAD(+)-permeable Cx43 to the phosphorylated, NAD(+)-impermeable form occurs via Ca(2+)-stimulated protein kinase C (PKC). Thus, a self-regulatory loop emerged in CD38(+) fibroblasts whereby high [Ca(2+)](i) restricts further Ca(2+) mobilization by cADPR via PKC-mediated disruption of the Cx43-CD38 cross-talk. This mechanism may avoid: (i) leakage of NAD(+) from cells; (ii) depletion of intracellular NAD(+) by CD38; (iii) overproduction of intracellular cADPR resulting in potentially cytotoxic [Ca(2+)](i). |
| Databáze: | OpenAIRE |
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