A possible immunosuppressant, cycloprodigiosin hydrochloride, obtained from Pseudoalteromonas denitrificans.
Cycloprodigiosin hydrochloride (cPrG.HCl), a member of the prodigiosin family, is a red pigment obtained from the marine bacterium Pseudoalteromonas denitrificans. cPrG.HCl markedly suppressed 3H-thymidine incorporation by concanavalin A stimulated murine splenocytes but had little effect on lipopolysaccharide dependent 3H-thymidine incorporation, indicating that cPrG.HCl acts as a selective inhibitor of T cell proliferation in the same way as other members of the prodigiosin family. cPrG.HCl inhibited the proliferation of the PMA stimulated Jurkat cells through an apoptotic process. Intriguingly, cPrG.HCl inhibited the H+ translocation by vacuolar type ATPase in chromaffin granule membranes without any effect on either its ATPase activity nor on the membrane conductance of phospholipid bilayers, suggesting that cPrG.HCl selectively uncouples H+ translocation from the ATPase reaction rather than acting as a non-specific ionophore. Since crystalline cPrG.HCl is highly stable, it raises the possibility of its therapeutic use as an immunosuppressant.
Kawauchi
K
K
Department of Life Science, Faculty of Science, Himeji Institute of Technology, Hyogo, Japan.
Shibutani
K
K
Yagisawa
H
H
Kamata
H
H
Nakatsuji
S
S
Anzai
H
H
Yokoyama
Y
Y
Ikegami
Y
Y
Moriyama
Y
Y
Hirata
H
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002837:Chromaffin Granules / Q000201:enzymology; D003208:Concanavalin A; D004247:DNA / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006088:Gram-Negative Aerobic Bacteria; D006801:Humans; D007166:Immunosuppressive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000201:enzymology; D019169:Jurkat Cells; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012623:Seawater; D018629:Spectrometry, Mass, Secondary Ion; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013936:Thymidine / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D007211:Indoles; D008070:Lipopolysaccharides; D011758:Pyrroles; D003208:Concanavalin A; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; C108328:cycloprodigiosin; D004247:DNA; D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases; D013936:Thymidine