The furin inhibitor hexa-D-arginine blocks the activation of Pseudomonas aeruginosa exotoxin A in vivo.
The Pseudomonas aeruginosa exotoxin A (PEA) protein requires furin-mediated cleavage for manifestation of toxicity. We show here that the small stable furin inhibitor hexa-D-arginine amide effectively blocks PEA-induced cell lysis and is itself noncytotoxic. Administration of hexa-D-arginine to PEA-treated mice significantly improves their survival rate and also decreases circulating levels of tumor necrosis factor alpha.
Sarac
Miroslav S
MS
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans 70112, USA.
Cameron
Angus
A
Lindberg
Iris
I
D036002:ADP Ribose Transferases / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D016466:CHO Cells; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005098:Exotoxins / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D045683:Furin; D051379:Mice; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000401:mortality; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000472:pathogenicity; D013381:Subtilisins / Q000037:antagonists & inhibitors*; D037521:Virulence Factors / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; D005098:Exotoxins; D045683:Furin; D010455:Peptides; D013381:Subtilisins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C015462:polyarginine