FIG. 7.

Inhibition of TNF-induced increase in VAC in parental L929 cells increases survival rate, and enhancing VAC increases TNF-induced cell death in PMCA4^mut cells. (A) Cells as indicated were treated with TNF in the presence or absence of A23187 for different periods of time. VAC (left panel) and cell viability (right panel) were measured. A23187 inhibited TNF-induced increase in VAC and cell death in parental cells. (B) Parental L929 (top panels) and PMCA^mut (lower panels) cells were treated with TNF in the presence or absence of different inhibitors of exocytosis as indicated: nocodazole (Noc), 10 μM; jasplakinolide (Jas), 0.3 μM; and MDL-12330A (MDL), 50 μM. VAC (left panels) and cell viability (right panels) were measured at different time points after TNF treatment. The exocytosis inhibitors did not influence the TNF-induced increase in VAC and cell death in parental cells. In contrast, inhibition of exocytosis enhanced the TNF-induced increase in VAC and cell death in PMCA^mut cells. (C) Parental and PMCA^mut cells were treated with either 0.3 mM sucrose (Suc) or 0.3 mM glucose (Glu) as indicated. The formation of sucrosomes induced by 0.3 mM sucrose was detected by AO staining, as shown in the left panel. The survival rate of these cells in response to TNF treatment is shown in the right panel. Sucrosomes enhanced TNF-induced cell killing in PMCA^mut cells.