English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  NAADP-mediated Ca2+ signaling via type 1 ryanodine receptor in T cells revealed by a synthetic NAADP antagonist

Dammermann, W., Zhang, B., Nebel, M., Cordiglieri, C., Odoardi, F., Kirchberger, T., et al. (2009). NAADP-mediated Ca2+ signaling via type 1 ryanodine receptor in T cells revealed by a synthetic NAADP antagonist. Proceedings of the National Academy of Sciences of the United States of America, 106(26), 10678-10683.

Item is

Files

show Files
hide Files
:
PNAS-2009-Dammermann-10678-83[1].pdf (Any fulltext), 2MB
Name:
PNAS-2009-Dammermann-10678-83[1].pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
open access article
License:
-

Locators

show

Creators

show
hide
 Creators:
Dammermann, W.1, Author
Zhang, B.1, Author
Nebel, M.1, Author
Cordiglieri, C.2, Author              
Odoardi, F.2, Author              
Kirchberger, T.1, Author
Kawakami, N.2, Author              
Dowden, J.1, Author
Schmid, F.1, Author
Dornmair, K.2, Author              
Hohenegger, M.1, Author
Flügel, A.2, Author              
Guse, A. H.1, Author
Potter, B. V. L.1, Author
Affiliations:
1[Zhang, Bo; Dowden, James; Potter, Barry V. L.] Univ Bath, Wolfson Lab Med Chem, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England.; [Dammermann, Werner; Nebel, Merle; Kirchberger, Tanja; Schmid, Frederike; Guse, Andreas H.] Univ Med Ctr Hamburg Eppendorf, Calcium Signaling Grp, Ctr Med Expt, Inst Biochem & Mol Biol Cellular Signal Transduct, D-20246 Hamburg, Germany.; [Odoardi, Francesca; Fluegel, Alexander] Gemeinnutzige Hertie Stiftung & Univ Med Ctr Gott, Inst Multiple Sclerosis Res, D-37073 Göttingen, Germany.; [Dornmair, Klaus] Univ Munich, Inst Clin Neuroimmunol, D-82152 Martinsried, Germany.; [Hohenegger, Martin] Med Univ Vienna, Inst Pharmacol, A-1090 Vienna, Austria.; [Fluegel, Alexander] Univ Munich, Inst Immunol, D-80336 Munich, Germany., ou_persistent22              
2Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              

Content

show
hide
Free keywords: antagonism; nucleotide; second messenger; synthesis
 Abstract: The nucleotide NAADP was recently discovered as a second messenger involved in the initiation and propagation of Ca2+ signaling in lymphoma T cells, but its impact on primary T cell function is still unknown. An optimized, synthetic, small molecule inhibitor of NAADP action, termed BZ194, was designed and synthesized. BZ194 neither interfered with Ca2+ mobilization by D-myo-inositol 1,4,5-trisphosphate or cyclic ADP-ribose nor with capacitative Ca2+ entry. BZ194 specifically and effectively blocked NAADP-stimulated [H-3] ryanodine binding to the purified type 1 ryanodine receptor. Further, in intact T cells, Ca2+ mobilization evoked by NAADP or by formation of the immunological synapse between primary effector T cells and astrocytes was inhibited by BZ194. Downstream events of Ca2+ mobilization, such as nuclear translocation of "nuclear factor of activated T cells" (NFAT), T cell receptor-driven interleukin-2 production, and proliferation in antigen-experienced CD4(+) effector T cells, were attenuated by the NAADP antagonist. Taken together, specific inhibition of the NAADP signaling pathway constitutes a way to specifically and effectively modulate T-cell activation and has potential in the therapy of autoimmune diseases.

Details

show
hide
Language(s): eng - English
 Dates: 2009-06-30
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 433290
ISI: 000267564300053
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Proceedings of the National Academy of Sciences of the United States of America
  Alternative Title : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 106 (26) Sequence Number: - Start / End Page: 10678 - 10683 Identifier: ISSN: 0027-8424