Bcl-2 maintains the mitochondrial membrane potential, but fails to affect production of reactive oxygen species and endoplasmic reticulum stress, in sodium palmitate-induced beta-cell death

• Background. Sodium palmitate causes apoptosis of beta-cells, and the anti-apoptotic protein Bcl-2 has been shown to counteract this event. However, the exact mechanisms that underlie palmitate-induced pancreatic beta-cell apoptosis and through which pathway Bcl-2 executes the protective effect are still unclear. Methods. A stable Bcl-2-overexpressing RINm5F cell clone (BMG) and its negative control (B45) were exposed to palmitate for up to 8 h, and cell viability, mitochondrial membrane potential (Delta psi m), reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress, and NF-kappa B activation were studied in time course experiments. Results. Palmitate exposure for 8 h resulted in increased cell death rates, and this event was partially counteracted by Bcl-2. Bcl-2 overexpression promoted in parallel also a delayed induction of GADD153/CHOP and a weaker phosphorylation of BimEL in palmitate-exposed cells. At earlier time points (2-4 h) palmitate exposure resulted in increased generation of ROS, a decrease in mitochondrial membrane potential (Delta psi m), and a modest increase in the phosphorylation of eIF2 alpha and IRE1 alpha. BMG cells produced similar amounts of ROS and displayed the same eIF2 alpha and IRE1 alpha phosphorylation rates as B45 cells. However, the palmitate-induced dissipation of Delta psi m was partially counteracted by Bcl-2. In addition, basal NF-kappa B activity was increased in BMG cells. Conclusions. Our results indicate that Bcl-2 counteracts palmitate-induced beta-cell death by maintaining mitochondrial membrane integrity and augmenting NF-kappa B activity, but not by affecting ROS production and ER stress.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Bcl-2

mitochondrial membrane integrity

NF-kappa B

palmitate

pancreatic beta cell death

reactive oxygen species

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