Site and mechanism of growth inhibition by prostaglandins. II. Temperature-dependent transfer of a cyclopentenone prostaglandin to nuclei.

Cyclopentenone prostaglandins (PGs) such as PGA2 and 9-deoxy-delta 9,12-13,14-dihydro-PGD2 (delta 12-PGJ2) are transported actively into the cytoplasm and exert growth inhibition in cultured cells. We examined effect of temperature on the uptake of delta 12-PGJ2 and its subsequent translocations within and out of the cells. When L-1210 murine leukemia cells were incubated with the PG at 4, 20 and 37 degrees C, the initial rate of uptake increased with temperature. However, the uptake at 37 degrees C declined rapidly after 5 min, whereas that at 4 and 20 degrees C increased linearly and reached plateau. Subcellular distribution study revealed that about 90% of the radioactivity taken up at 4 and 20 degrees C was present in the cytoplasm, whereas more than 50% of the radioactivity transported at 37 degrees C accumulated in the nuclei. When incubation temperature was shifted from 4 to 37 degrees C during incubation, significant accumulation of the radioactivity in the nuclei occurred at 37 degrees C. In contrast, when the cells were first incubated with delta 12-PGJ2, then washed and incubated without the PG at either 20 or 37 degrees C, most of the radioactivity found in the cytoplasm was effluxed to the medium during the second incubation. The rate of this efflux was negligible at 4 degrees C but increased with temperature above 20 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)