cNMP-AMs mimic and dissect bacterial nucleotidyl cyclase toxin effects.
Biochem Biophys Res Commun
; 451(4): 497-502, 2014 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-25108158
ABSTRACT
In addition to the well-known second messengers cAMP and cGMP, mammalian cells contain the cyclic pyrimidine nucleotides cCMP and cUMP. The Pseudomonas aeruginosa toxin ExoY massively increases cGMP and cUMP in cells, whereas the Bordetella pertussis toxin CyaA increases cAMP and, to a lesser extent, cCMP. To mimic and dissect toxin effects, we synthesized cNMP-acetoxymethylesters as prodrugs. cNMP-AMs rapidly and effectively released the corresponding cNMP in cells. The combination of cGMP-AM plus cUMP-AM mimicked cytotoxicity of ExoY. cUMP-AM and cGMP-AM differentially activated gene expression. Certain cCMP and cUMP effects were independent of the known cNMP effectors protein kinases A and G and guanine nucleotide exchange factor Epac. In conclusion, cNMP-AMs are useful tools to mimic and dissect bacterial nucleotidyl cyclase toxin effects.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Toxinas Bacterianas
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Uridina Monofosfato
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GMP Cíclico
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Nucleotídeos Cíclicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article