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Cellular effects an...
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Kirchberger, TanjaUniversity Medical Centre Hamburg-Eppendorf, Germany.
(författare)
Cellular effects and metabolic stability of N1-cyclicinosinediphosphoribose and its derivatives
- Artikel/kapitelEngelska2006
Förlag, utgivningsår, omfång ...
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2009-01-29
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John Wiley & Sons,2006
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printrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:liu-81991
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-81991URI
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https://doi.org/10.1038/sj.bjp.0706869DOI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Background and purpose:Recently, a number of mimics of the second messenger cyclic ADP-ribose (cADPR) with replacement of adenosine by inosine were introduced. In addition, various alterations in the molecule ranging from substitutions at C8 of the base up to full replacement of the ribose moieties still retained biological activity. However, nothing is known about the metabolic stability and cellular effects of these novel analogues.Experimental approach:cADPR and the inosine-based analogues were incubated with CD38, ADP-ribosyl cyclase and NAD-glycohydrolase and metabolism was analysed by RP-HPLC. Furthermore, the effect of the analogues on cytokine expression and proliferation was investigated in primary T-lymphocytes and T-lymphoma cells.Key results:Incubation of cADPR with CD38 resulted in degradation to adenosine diphosphoribose. ADP-ribosyl cyclase weakly catabolised cADPR whereas NAD-glycohydrolase showed no such activity. In contrast, N1-cyclic inosine 5′-diphosphoribose (N1-cIDPR) was not hydrolyzed by CD38. Three additional N1-cIDPR analogues showed a similar stability. Proliferation of Jurkat T-lymphoma cells was inhibited by N1-cIDPR, N1-[(phosphoryl-O-ethoxy)-methyl]-N9-[(phosphoryl-O-ethoxy)-methyl]-hypoxanthine-cyclic pyrophosphate (N1-cIDP-DE) and N1-ethoxymethyl-cIDPR (N1-cIDPRE). In contrast, in primary T cells neither proliferation nor cytokine expression was affected by these compounds.Conclusions and Implications:The metabolic stability of N1-cIDPR and its analogues provides an advantage for the development of novel pharmaceutical compounds interfering with cADPR mediated Ca2+ signalling pathways. The differential effects of N1-cIDPR and N1-cIDPRE on proliferation and cytokine expression in primary T cells versus T-lymphoma cells may constitute a starting point for novel anti-tumor drugs.
Ämnesord och genrebeteckningar
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cyclic ADP-ribose
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ADP-ribosyl cyclase
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CD38
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T-lymphoma cell
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primary T cell
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stable analogues
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calcium signalling
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proliferation
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cytokine expression
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signal transduction
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Wagner, GUniversity of Bath, UK
(författare)
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Xu, JianfengPeking University, Beijing, China
(författare)
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Cordiglieri, CMax-Planck-Institute for Neurobiology, Martinsried, Germany
(författare)
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Wang, P.Peking University, Beijing, China
(författare)
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Gasser, AndreasUniversity Medical Centre Hamburg-Eppendorf, Germany.
(författare)
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Fliegert, RalfUniversity Medical Centre Hamburg-Eppendorf, Germany.
(författare)
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Bruhn, Sören,1976-University Medical Centre Hamburg-Eppendorf, Germany.(Swepub:liu)sorbr27
(författare)
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Flügel, AndreasMax-Planck-Institute for Neurobiology, Martinsried, Germany
(författare)
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Lund, FrenTrudeau Institute, Saranac Lake, NY, USA
(författare)
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Zhang, LeePeking University, Beijing, China
(författare)
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Potter, BarryUniversity of Bath, UK
(författare)
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Guse, AndreasUniversity Medical Centre Hamburg-Eppendorf, Germany.
(författare)
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University Medical Centre Hamburg-Eppendorf, Germany.University of Bath, UK
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:British Journal of Pharmacology: John Wiley & Sons149:40007-11881476-5381
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Kirchberger, Tan ...
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Wagner, G
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Xu, Jianfeng
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Cordiglieri, C
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Wang, P.
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Gasser, Andreas
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Fliegert, Ralf
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Bruhn, Sören, 19 ...
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Flügel, Andreas
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Lund, Fren
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Zhang, Lee
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Potter, Barry
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Guse, Andreas
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