Chicken anti-Human Aprataxin polyclonal antibody

Dendrobatid poison frogs readily accumulate alkaloids from diet into skin, where such compounds serve as a chemical defense against predators. Arthropods seem to be the source of decahydroquinolines (DHQs), several izidines, coccinellines, spiropyrrolizidines, pumiliotoxins (PTXs), and allopumiliotoxins (aPTXs). A DHQ iso-223F, and PTX (+)-251D were fed to poison frogs of the dendrobatid genera Dendrobates, Epipedobates, and Phyllobates. The two alkaloids were accumulated in skin unchanged except for the three species of Dendrobates, where approximate to80% of accumulated PTX (+)-251D was stereoselectively hydroxylated to aPTX (+)-267A. The unnatural enantiomer PTX (-)-251D was accumulated efficiently when fed to Dendrobates auratus, but was not hydroxylated. The enantiomers of IPTX 251D and their desmethyl analogs were synthesized from N-Boc-protected (-)- and (+)-proline methyl esters. Both PTX (+)-251D and aPTX (+)-267A proved to be potent convulsants in mice, with (+)-267A being approximate to5-fold more toxic than (+)-251D. Both alkaloids were hyperalgesic at the site of injection. The unnatural PTX (-)-251D caused no overt effect in mice. Thus, the evolutionary development of a pumiliotoxin 7-hydroxylase would have provided frogs of the genus Dendrobates with a means of enhancing the antipredator potency of ingested PTXs.

The level of intracellular diadenosine 5', 5 '''-P-1,P-4-tetraphosphate (Ap(4)A) increases several fold in mammalian cells treated with non-cytotoxic doses of interstrand DNA-crosslinking agents such as mitomycin C. It is also increased in cells lacking DNA repair proteins including XRCC1, PARP1, APTX and FANCG, while >50-fold increases (up to around 25 mu M) are achieved in repair mutants exposed to mitomycin C. Part of this induced Ap(4)A is converted into novel derivatives, identified as mono- and di-ADP-ribosylated Ap(4)A. Gene knockout experiments suggest that DNA ligase III is primarily responsible for the synthesis of damage-induced Ap(4)A and that PARP1 and PARP2 can both catalyze its ADP-ribosylation. Degradative proteins such as aprataxin may also contribute to the increase. Using a cell-free replication system, Ap(4)A was found to cause a marked inhibition of the initiation of DNA replicons, while elongation was unaffected. Maximum inhibition of 70-80% was achieved with 20 mu M Ap(4)A. Ap(3)A, Ap(5)A, Gp(4)G and ADP-ribosylated Ap(4)A were without effect. It is proposed that Ap(4)A acts as an important inducible ligand in the DNA damage response to prevent the replication of damaged DNA. (C) 2015 Elsevier B.V. All rights reserved.