Schematic representation of mechanism coupling oxidized LDL to beta cell dysfunction and death.

<p>Schematic representation of mechanism coupling oxidized LDL to beta cell dysfunction and death.</p

Effects of 4-BPA chemical chaperone on the loss of insulin expression caused by human oxidized LDL.

<p>The preproinsulin mRNA was quantified in MIN6 cells (<b>a)</b> and (<b>b</b>) human islets. Cells were exposed to vehicle (V), human native LDL (nLDL) or oxidized LDL (oxLDL) 2 mmol/l cholesterol, in the presence or absence of PBA 2.5 mmol/l (filled bars) for 48 h. The mRNA levels were normalized against the <i>Rplp0/RPLP0</i> and the expression levels from cells cultured with vehicle were set to 100%. Data are the mean of ± SEM of 3 independent experiments performed in triplicate (*, P<0.05).</p

Role of oxidative stress on the ER stress markers expression induced by human oxidized LDL.

<p>Expression of <i>CHOP</i>/<i>Chop</i> and <i>P58IPK</i>/<i>p58IPK</i> in <b>(a)</b> MIN6 and <b>(b)</b> human islets cells exposed to hydrogen peroxide (H₂O₂) 150 μM at indicated times. The expression of the two genes was quantified in <b>(c)</b> MIN6 cells or <b>(d)</b> human islets that were co-incubated with vehicle (V), human native LDL (nLDL) or oxidized LDL (oxLDL) 2 mmol/l cholesterol supplemented by either DMSO (control, open bar) or N-acetylcystein (NAC, filled bar) 1 mmol/l for MIN6 and 10 mmol/l for human islets cells. The results were normalized against <i>Rplp0</i>/<i>RPLP0</i> and the expression levels from cells cultured with vehicle were set to 100%. Data are the mean ± SEM of 3 independent experiments performed in triplicate (***, P<0.001; **, P<0.01).</p

Effects of Chop silencing in apoptosis caused by human oxidized LDL.

<p>MIN6 cells were transfected with a control RNA si-GFP duplex (Ctrl, <i>open bar</i>) or with siCHOP (<i>filled bar</i>). Thereafter, the cells were cultured for 72 h with vehicle (V) or oxidized LDL (oxLDL) 2 mmol/l cholesterol. The fraction of cells undergoing apoptosis was determined by scoring the percentage of cells displaying pyknotic nuclei. Data are the mean of ± SEM of 3 independent experiments performed in triplicate (**, P<0.01).</p

Effects of BPA on apoptosis evoked by human oxidized LDL.

<p>Measurement of apoptotic cells in <b>(a)</b> MIN6 and <b>(b)</b> isolated human islets. MIN6 cells were cultured with vehicle (V), native LDL (nLDL) or oxidized LDL (oxLDL) 2 mmol/l cholesterol with or without PBA 2.5 mmol/l (filled bar) for 72 h. The fraction of cells undergoing apoptosis was determined by scoring the percentage of cells displaying pyknotic nuclei. Data are the mean of ± SEM of 3 independent experiments (***, P<0.001; *, P<0.05). Quantification of the anti-apoptotic <i>Bcl2/BCL2</i> and <i>Ib1</i>/<i>IB1</i> mRNA levels in <b>(c)</b> MIN6 and <b>(d)</b> isolated human islets. The mRNA level of the two genes was quantified by quantitative real-time PCR and was normalized against the <i>Rplp0/RPLP0</i>. The expression levels from cells cultured with vehicle were set to 100%. Data are the mean of ± SEM of 3 independent experiments performed in triplicate (***, P<0.001; *, P<0.05).</p