Prodigiosin 25-C uncouples vacuolar type H(+)-ATPase, inhibits vacuolar acidification and affects glycoprotein processing.
Prodigiosin 25-C inhibited the accumulation of 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine and acridine orange in the acidic compartments of baby hamster kidney cells with little perturbation of cellular ATP levels. In rat liver lysosomes, prodigiosin 25-C inhibited the proton pump activity with an IC50 of approximately 30 nM, but did not affect ATPase activity up to 1 microM. It also delayed the transport of vesicular stomatitis virus G protein and induced a drastic swelling of Golgi apparatus and mitochondria. These results indicate that prodigiosin 25-C raises the pH of acidic compartments through inhibition of the proton pump activity of vacuolar type H(+)-ATPase, thereby causing the functional and morphological changes to the Golgi apparatus.
Department of Bioengineering, Tokyo Institute of Technology, Kanagawa, Japan.
T
T
Kataoka
M
M
Muroi
S
S
Ohkuma
T
T
Waritani
J
J
Magae
A
A
Takatsuki
S
S
Kondo
M
M
Yamasaki
K
K
Nagai
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D006023:Glycoproteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000187:drug effects / Q000648:ultrastructure; D006863:Hydrogen-Ion Concentration; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism / Q000648:ultrastructure; D008099:Liver / Q000201:enzymology / Q000648:ultrastructure; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D008854:Microscopy, Electron; D008933:Mitochondrial Swelling / Q000187:drug effects; D011353:Prodigiosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D014617:Vacuoles / Q000201:enzymology*
D006023:Glycoproteins; D007166:Immunosuppressive Agents; D054328:Proton Pump Inhibitors; C077331:prodigiosin 25C; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; D011353:Prodigiosin