Ganglioside GD3 enhances apoptosis by suppressing the nuclear factor-κB-dependent survival pathway

Abstract

SPECIFIC AIMGlycosphingolipidshave emerged as cell death effectors because of their role in apoptosis signaling. Because cell survival reflects a balance between death and survival pathways and because the nuclear factor-κB (NF-κB) is known to downregulate apoptosis in response to diverse stimuli, our study examined the role of ganglioside GD3 (GD3) and related structural analogs, including short-chain ceramide analogs—for example, ceramide C2 (C2)—on NF-κB regulation, mitochondrial reactive oxygen species (ROS) generation, and survival of cultured rat hepatocytes.PRINCIPAL FINDINGS1. Mitochondrial ROS formation is common for both C2 and GD3Incubation of hepatocytes with C2 and GD3 (0–50 μM) resulted in a similar dose-dependent peroxide formation. It is interesting that, despite this, hepatocytes displayed a selective susceptibility to GD3 treatment, which was reflected by a decreased survival (36±5% vs. 92±7% for GD3 and C2 at 50 μM for 12 h), which was accompanied by apoptotic features. Inhibitors of mi...