Proteasome inhibition-induces endoplasmic reticulum dysfunction and cell death of human cholangiocarcinoma cells

Figure 4 A: Morphologic features of apoptosis induced by proteasome inhibitors, MG132 and bortezomib in KMCH cells. On the left up panel, transmission electron microscopic appearance of untreated cholangiocarcinoma cell is depicted (bar = 0.5 μm). In the right up panel, exposure to MG132 (1 μmol/L ) for 24 h results in a distinctly dilated ER (arrowhead) (bar = 2 μm) . On the bottom-left panel, similar results are observed with MG 132 (0.5 μmol/L) for 24 h (arrowhead) (bar = 2 μm). Note apoptotic morphology also characterized by condensation of heterochromatin; On the bottom-right panel, high magnification image of cytoplasm shows dilated ER (arrowhead) (bar = 2 μm); B: Ca_i⁺⁺ increases following treatment with proteasome inhibitors in KMCH cells. The time course of Ca_i⁺⁺ changes is demonstrated. At 24 h, Ca_i⁺⁺ levels were significantly increased in MG132 1 mol/L and Bortezomib 1 μmol/L treated cells than untreated KMCH cells (P < 0.05); C: Intracellular Ca_i⁺⁺ chelation with BAPTA does not prevent apoptosis by MG132.