penicillic acid :

1: J Biol Chem 2003 Feb 21;278(8):5786-93  
The mycotoxin penicillic acid inhibits Fas ligand-induced apoptosis by blocking self-processing of caspase-8 in death-inducing signaling complex.

Bando M, Hasegawa M, Tsuboi Y, Miyake Y, Shiina M, Ito M, Handa H, Nagai K, Kataoka T.

Research Center for Experimental Biology and Department of Bioengineering, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.

Upon engagement with Fas ligand (FasL), Fas rapidly induces recruitment and self-processing of caspase-8 via the adaptor protein Fas-associated death domain (FADD), and activated caspase-8 cleaves downstream substrates such as caspase-3. We have found that penicillic acid (PCA) inhibits FasL-induced apoptosis and concomitant loss of cell viability in Burkitt's lymphoma Raji cells. PCA prevented activation of caspase-8 and caspase-3 upon treatment with FasL. However, PCA did not affect active caspase-3 in FasL-treated cells, suggesting that PCA primarily blocks early signaling events upstream of caspase-8 activation. FasL-induced processing of caspase-8 was severely impaired in the death-inducing signaling complex, although FasL-induced recruitment of FADD and caspase-8 occurred normally in PCA-treated cells. Although PCA inhibited the enzymatic activities of active recombinant caspase-3, caspase-8, and caspase-9 at similar concentrations, PCA exerted weak inhibitory effects on activation of caspase-9 and caspase-3 in staurosporine-treated cells but strongly inhibited caspase-8 activation in FasL-treated cells. Glutathione and cysteine neutralized an inhibitory effect of PCA on caspase-8, and PCA bound directly to the active center cysteine in the large subunit of caspase-8. Thus, our present results demonstrate that PCA inhibits FasL-induced apoptosis by targeting self-processing of caspase-8.

PMID: 12482880




[top] This page was done by a student of Bioinformatics, Open University Jerusalem Israel, in a homage to Fermentek and to Dr Berend.
 4mg  noneto biocompare formulae omd ToxicPlants DictCellBio MolBioDict ( test  position )
BioChemical Suppliers
A23187 Actinomycin Aflatoxin Anisomycin Aphidicolin Ascomycin


Cerulenin Chromomycin Geldanamycin Cyclopiazonic acid
Cytochalasin Forskolin Fumagillin Fumonisin Hypericin K252a
KT5823 Mitomycin Nigericin Ochratoxin Oligomycin Mycophenolic acid
Paclitaxel Patulin Paxilline Penitrem Puromycin Penicillic acid
Radicicol Rapamycin Staurosporine Sterigmatocystin Thapsigargin Tunicamycin
 Verruculogen  Wortmannin