Effect of unsaturated bonds in the sn-2 acyl chain of phosphatidylcholine on the membrane-damaging action of Clostridium perfringens alpha-toxin toward liposomes.
Clostridium perfringens alpha-toxin degrades phosphatidylcholine (PC) in the bilayer of liposomes and destroys the membrane. The effect of the type and position of unsaturation in the fatty acyl chain of PC (18:0/18:1 PC) synthesized on the toxin-induced leakage of carboxyfluorescein (CF) from PC liposomes was examined. Differential scanning calorimetry showed that the phase transition temperature (T(m)) was minimal when the triple bond was positioned at C (9) in the sn-2 acyl chain. The toxin-induced CF leakage decreased with the migration of the bond from C (9) to either end of the acyl chain in PC. The PC containing the cis-double bond had a similar T(m) to that with the triple bond, but a lower value than the PC containing the trans-double bond. Furthermore, the toxin-induced leakage from liposomes composed of PC containing the cis-double bond resembled that with PC having the triple bond and was greater than that from liposomes with PC having the trans-double bond. The binding of a H148G mutant to PC liposomes showed a reciprocal relationship in terms of the T(m) value of PC containing the triple bond. These results indicate that the toxin-induced membrane damage is closely related to membrane fluidity in liposomes.
Nagahama
Masahiro
M
Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan.
Otsuka
Akiko
A
Oda
Masataka
M
Singh
Rajesh K
RK
Ziora
Zyta M
ZM
Imagawa
Hiroshi
H
Nishizawa
Mugio
M
Sakurai
Jun
J
D001427:Bacterial Toxins / Q000633:toxicity*; D002135:Calcium-Binding Proteins / Q000633:toxicity*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008560:Membrane Fluidity; D044367:Phase Transition; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism; D013696:Temperature; D010738:Type C Phospholipases / Q000633:toxicity*
D001427:Bacterial Toxins; D002135:Calcium-Binding Proteins; D008081:Liposomes; D010713:Phosphatidylcholines; D010738:Type C Phospholipases; C040649:alpha toxin, Clostridium perfringens