Membrane permeabilization induced by discodermin A, a novel marine bioactive peptide.
The effects of discodermin A (DC-A), a novel marine bioactive peptide extracted from sea sponge Discodermia kiiensis, on the vascular smooth muscle cells and tissues were examined. Analysis with a confocal laser microscope showed that DC-A (0.1-30 microM) permeabilized the plasma membrane of A10 cells to the non-permeable fluorescent agents, ethidium homodimer-1 (MW = 857) and calcein (MW = 623), in a concentration-dependent manner. In the vascular tissue treated with 30 microM DC-A, addition of a micromolar concentration of Ca(2+) evoked a sustained contraction in the presence of ATP, suggesting that DC-A increased the permeability of the membrane to Ca(2+) and ATP. DC-A at higher concentrations (30 microM) significantly increased the leakage of lactate dehydrogenase (140 kD) from the vascular tissue. These results suggest that DC-A has a permeabilizing effect on the plasma membrane possibly by interacting with plasma membrane phospholipids with its six successive hydrophobic amino acid residues at N-terminal.
Sato
K
K
Radio Isotope Center, Graduate School of Agriculture and Life Studies, The University of Tokyo, Bunkyo-Ku, Tokyo 113-8657, Japan. akoita@mail.ecc.u-tokyo.ac.jp
Horibe
K
K
Amano
K
K
Mitusi-Saito
M
M
Hori
M
M
Matsunaga
S
S
Fusetani
N
N
Ozaki
H
H
Karaki
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D029845:Amphibian Proteins; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D004996:Ethidium / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011817:Rabbits; D051381:Rats
D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides; D005452:Fluoresceins; D005456:Fluorescent Dyes; D000255:Adenosine Triphosphate; C045398:discodermin A, Discodermia kiiensis; D004996:Ethidium; D002118:Calcium; C007740:fluorexon