Document Detail


Synthesis and use of cell-permeant cyclic ADP-ribose.
MedLine Citation:
PMID:  22274607     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cyclic ADP-ribose (cADPR) is a second messenger that acts on ryanodine receptors to mobilize Ca(2+). cADPR has a net negative charge at physiological pH making it not passively membrane permeant thereby requiring it to be injected, electroporated or loaded via liposomes. Such membrane impermeance of other charged intracellular messengers (including cyclic AMP, inositol 1,4,5-trisphosphate and nicotinic acid adenine dinucleotide phosphate) and fluorescent dyes (including fura-2 and fluorescein) has been overcome by synthesizing masked analogs (prodrugs), which are passively permeant and hydrolyzed to the parent compound inside cells. We now report the synthesis and biological activity of acetoxymethyl (AM) and butoxymethyl (BM) analogs of cADPR. Extracellular addition of cADPR-AM or cADPR-BM to neuronal cells in primary culture or PC12 neuroblastoma cells induced increases in cytosolic Ca(2+). Pre-incubation of PC12 cells with thapsigargin, ryanodine or caffeine eliminated the response to cADPR-AM, whereas the response still occurred in the absence of extracellular Ca(2+). Combined, these data demonstrate that masked cADPR analogs are cell-permeant and biologically active. We hope these cell-permeant tools will facilitate cADPR research and reveal its diverse physiological functions.
Authors:
Daniel Rosen; Duncan Bloor-Young; James Squires; Raman Parkesh; Gareth Waters; Sridhar R Vasudevan; Alexander M Lewis; Grant C Churchill
Related Documents :
2828177 - A purine-rich dna sequence motif present in sv40 and lymphotropic papovavirus binds a l...
22363477 - Study of local hydrodynamic environment in cell-substrate adhesion using side-view μpi...
16659407 - Mechanical inhibition of hypocotyl elongation induces radial enlargement: implications ...
12091477 - Repression of myelin proteolipid protein gene expression is mediated through both gener...
2668087 - Antagonistic effects of laminin and fibronectin on the expression of the myogenic pheno...
17448587 - Revisiting the astrocyte-oligodendrocyte relationship in the adult cns.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-17
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  418     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-13     Completed Date:  2012-04-09     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  353-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport
Caffeine / pharmacology
Calcium / metabolism
Cell Membrane Permeability* / drug effects
Cyclic ADP-Ribose / analogs & derivatives*,  chemical synthesis,  metabolism*
PC12 Cells
Rats
Ryanodine / pharmacology
Sea Urchins
Thapsigargin / pharmacology
Grant Support
ID/Acronym/Agency:
PG/09/056/27846//British Heart Foundation
Chemical
Reg. No./Substance:
119340-53-3/Cyclic ADP-Ribose; 15662-33-6/Ryanodine; 3G6A5W338E/Caffeine; 67526-95-8/Thapsigargin; SY7Q814VUP/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Differences in the catalytic mechanisms of mesophilic and thermophilic indole-3-glycerol phosphate s...
Next Document:  The quorum sensing transcriptional regulator TraR has separate binding sites for DNA and the anti-ac...