FIGURE 2.

OxLDL protects primary MM cells from bortezomib-induced cytotoxicity and suppresses bortezomib-induced inhibition of proteasome activity and proapoptotic unfolded protein response signaling. A, Proliferation of primary patient MM cells exposed to 35 nM bortezomib (BTZ) for 72 hours in the presence of 50 μg/mL Cu²⁺-OxLDL. Proliferation was assessed by MTS assay. Data are expressed as the mean ± SE of the % of control from an assay performed in quadruplicate for each patient sample. B, Proliferation of U266 cells exposed to 6 nM BTZ for 48 hours in the presence of 50 μg/mL Cu²⁺-OxLDL, acetylated LDL (AcLDL), minimally modified LDL (mmLDL) or carbamylated LDL (cLDL). Proliferation was assessed by MTS assay. Data are expressed as the mean ± SE of the % of control from three independent experiments performed in quadruplicate. C, Proteasome activity of U266 cells following exposure to 6 nM BTZ for 3 to 24 hours in the presence or absence of 50 μg/mL mmLDL or nLDL. Representative western blot of ubiquitin accumulation and PARP cleavage (full length and cleaved) following exposure of U266 (D) or MM1S (E) cells to 6 nM BTZ for 3 to 24 hours in the presence or absence of 50 μg/mL mmLDL. F, Representative western blot of ubiquitin (Ub) accumulation, PARP (full length/cleaved), phosphorylated JNK (p-JNK), and phosphorylated eIF2alpha (p-eIF2α) following exposure of U266 cells to 6 nM BTZ for 24 hours in the presence of 50 μg/mL nLDL or mmLDL. G, Representative western blot of ubiquitin (Ub) accumulation and PARP (full length/cleaved) following exposure of MM1S cells to 6 nM BTZ for 24 hours in the presence of 50 μg/mL nLDL or mmLDL. H, Proteasome activity of U266 cells following exposure of U266 cells to 20 μM H₂O₂ ± 500 U/mL catalase or 6 nM BTZ ± 500 U/mL superoxide dismutase (SOD) ± 500 U/mL catalase ±50 μg/mL mmLDL for 3 hours. Chymotrypsin-like proteasome activity in (C and H) was assessed as described in Section 2. Data are presented as mean ± SE of the % of control from four independent experiments performed in quadruplicate