INVESTIGADORES
DELFINO jose maria
artículos
Título:
Dimeric procyanidins are inhibitors of NF-kappa-B-DNA binding
Autor/es:
MACKENZIE GG; JM DELFINO; KEEN CL; FRAGA CG; OTEIZA PI
Revista:
BIOCHEMICAL PHARMACOLOGY
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Año: 2009 vol. 78 p. 1252 - 1262
ISSN:
0006-2952
Resumen:
Given the central role of the transcription factor NF-kB in inflammation, molecules that can inhibit NFkB are being actively investigated. The present work characterize potential interactions between dimeric
procyanidins [B-type (B1 and B2) and A-type (A1 and A2)] and NF-kB proteins. B1 and B2, inhibited
tumor necrosis factor a (TNFa)- and phorbol 12-myristate 13-acetate (PMA)-induced transactivation of
NF-kB-driven genes and the increase of NF-kBDNA nuclear binding in Jurkat T cells. B1 and B2, added in
vitro to nuclear fractions, inhibited NF-kB binding to its DNA consensus sequence. B1 and B2 prevented
the binding of RelA and p50 recombinant proteins to its DNA consensus sequence. All these effects were
not observed with A1 and A2. Putative molecular models for possible interactions of B1, B2, A1 and A2,
with NF-kB proteins were constructed, indicating that B-type dimeric procyanidins have higher
possibilities of chemical interactions with NF-kB than A-type dimeric procyanidins. The results support
the concept that B-type dimeric procyanidins can provide anti-inflammatory benefits due to their ability
to reduce NF-kB binding to the DNA.