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Review
. 2011 Feb 22;16(2):1854-77.
doi: 10.3390/molecules16021854.

The ups and downs of tannins as inhibitors of poly(ADP-ribose)glycohydrolase

Christian Blenn  1 , Philippe Wyrsch, Felix R Althaus
Affiliations
Review

The ups and downs of tannins as inhibitors of poly(ADP-ribose)glycohydrolase

Christian Blenn et al. Molecules. .

Abstract

DNA damage to cells activates nuclear poly(ADP-ribose)polymerases (PARPs) and the poly(ADP-ribose) (PAR) synthesized is rapidly cleaved into ADP-ribose (ADPR) by PAR glycohydrolase (PARG) action. Naturally appearing tannin-like molecules have been implicated in specific inhibition of the PARG enzyme. This review deals with the in vitro and in vivo effects of tannins on PAR metabolism and their downstream actions in DNA damage signaling.

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Figures

Figure 1
Figure 1
Poly(ADP-ribose) metabolism. In response to DNA damage, nuclear poly(ADP-ribose)polymerases (PARP-1 and PARP-2) hydrolyze NAD+, releasing ADPR, nicotinamide and H+. This reaction is induced by the formation of an ester bond between the amino acid-acceptors glutamic acid, aspartic acid or COOH-lysine and the first ADP-ribose (ADPR, marked in blue). Elongation occurs at the 2′-OH of the ribose moiety whereas branching occurs at the 2″-OH position resulting in poly(ADPR) (PAR), a multi-branched polyanion. Poly(ADPR)glycohydrolase (PARG) is a catabolic enzyme with an endo- and exoglycosidic activity. It cleaves the glycosidic bonds between the ADPR units, resulting in free PAR and finally ADPR.
Figure 2
Figure 2
Chemical structures of galloyl derivates tested as PARG inhibitors with efficiency in cells and/or in vitro.
See this image and copyright information in PMC

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