Inhibition of iron toxicity in rat hepatocyte cultures by pyoverdin Pa A, the peptidic fluorescent siderophore of Pseudomonas aeruginosa.
The effect of pyoverdin Pa A (an iron chelator isolated and purified from Pseudomonas aeruginosa ATCC 15692) was studied in rat hepatocyte cultures overloaded with iron. Iron overload was achieved by adding 80 mum-ferric nitrilotriacetate to the culture medium. One day after iron treatment, significant increases in aspartate aminotransferase and lactate dehydrogenase in the culture medium were measured; under similar conditions, albumin and transferrin secretions were decreased. Pyoverdin Pa A (100 mum in the medium) appeared to be as effective as desferrioxamine B (100 mum) in the protection of hepatocytes, cultured for 1 day in the presence of 80 mum-ferric nitrilotriacetate, against the toxic effects of iron overload. In rat hepatocytes cultured for 1 day in the presence of 1 mum Fe(55), pyoverdin Pa A or desferrioxamine B in the medium decreased iron uptake by the cells. When hepatocytes were cultured for 1 day in the presence of 1 mum-Fe(55) and then for a further day in the presence of 100 mum-Pa A or desferrioxamine but not iron, both chelators decreased the intracellular iron level and increased the concentration of the metal in the culture medium.
Jégo
P
P
Liver Research Unit, INSERM U49, Pontchaillou University Hospital, 35033 Rennes Cedex, France.
Hubert
N
N
Moirand
R
R
Morel
I
I
Pasdeloup
N
N
Ocaktan
A
A
Abdallah
M
M
Brissot
P
P
Lescoat
G
G