Effect of glutathione content on cellular uptake and growth inhibitory activity of prostaglandin A2 in L-1210 cells.
Prostaglandin A2 (PGA2) is known to be actively incorporated into mammalian cells and thereby evokes its biological effects. To explore the transport mechanism of PGA2 and the possible role of cellular glutathione (GSH) in the transport process, we prepared GSH-enriched and -depleted L-1210 cells and then incubated with [3H] PGA2. In GSH-depleted cells, the total amount of PGA2 incorporated was reduced to about 50% of that in the control and GSH-enriched cells, accompanied by marked reduction of the PG in the cytosol but not in the nuclei. The kinetics of uptake revealed that the apparent Vmax was reduced by GSH depletion. Subsequent study of L-1210 cells under culture conditions provided similar results; GSH-depletion caused suppression of PG uptake and a reduction in the amount of PGA2 in cytosol, while its nuclear accumulation was little influenced. Comparison of the effect of PGA2 on the growth of control and GSH-depleted cells showed that the PG suppressed cell proliferation to the same extent. Our results suggest that, though uptake of PGA2 may be significantly influenced, its accumulation, and hence the manifestation of its biological effects are not influenced by GSH status.
Ohno
K
K
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Hirata
M
M
Narumiya
S
S
Fukushima
M
M
D000818:Animals; D001693:Biological Transport, Active; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D005978:Glutathione / Q000502:physiology*; D007700:Kinetics; D007939:Leukemia L1210 / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D011454:Prostaglandins A / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D011454:Prostaglandins A; D005978:Glutathione; C100008:prostaglandin A2