Inhibitory effect of acyl-CoA and acyl-carnitine compounds on the ischemia-inducing activity of Bordetella heat-labile toxin in guinea pig skin.
The ability of Bordetella heat-labile toxin (HLT) to induce ischemic lesions after intracutaneous injection to guinea pig skin was lost following incubation at 37 degrees C with long-chain saturated acyl-CoA and acyl-carnitine compounds. Short-chain unsaturated acyl-CoA compounds, however, were less potent in inhibiting the induction of HLT activity. Long-chain saturated acyl-CoA and acyl-carnitine compounds, potently inhibited the induction of this activity. On incubation with HLT at 0 degrees C, a long-chain saturated acyl-CoA compound, palmitoyl-CoA, did not inhibit HLT activity. When first mixed with bovine serum albumin or dimethyl-beta-cyclodextrin, palmitoyl-CoA lost the ability to inhibit HLT activity. Binding of 14C-palmitoyl-CoA to HLT was measured by Scatchard analysis. The Bmax values of HLT (2.75 mol/mol of protein) were higher than that of acyl-CoA-binding protein from bovine liver (0.95 mol/mol of protein). Neither acyl-CoA hydrolase nor acyl-CoA ligase was detected in the HLT preparation. These results suggest that the acyl-CoA and acyl-carnitine compounds bind directly to HLT and produce a critical change in conformation required for HLT activity.
Nagai
M
M
Department of Microbiology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Watanabe
M
M
Endoh
M
M
Danbara
H
H
D000214:Acyl Coenzyme A / Q000494:pharmacology*; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D001884:Bordetella / Q000737:chemistry*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006168:Guinea Pigs; D007511:Ischemia / Q000139:chemically induced / Q000517:prevention & control*; D012867:Skin / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D011503:Transglutaminases; D010566:Virulence Factors, Bordetella
D000214:Acyl Coenzyme A; D001427:Bacterial Toxins; D005231:Fatty Acids, Unsaturated; D010566:Virulence Factors, Bordetella; C060969:dermonecrotic toxin, Bordetella; D011503:Transglutaminases; D002331:Carnitine