Stearate-induced apoptosis in human pancreatic β-cells is associated with changes in membrane protein expression and these changes are inhibited by oleate
Abstrakt
PURPOSE: Lipotoxicity is implicated in type 2 diabetes pathogenesis. Its molecular mechanisms are not completely understood.
The aim of this study is to identify new suspect proteins involved in pancreatic β-cell death induction by saturated fatty acids and its inhibition by unsaturated fatty acids. EXPERIMENTAL DESIGN: Employing 2DE analysis and subsequent western blot confirmation, we assessed the differences in membrane/membrane-associated protein expression in human β-cell line NES2Y during cell death induction by stearate and its inhibition by oleate.
RESULTS: Induction of apoptosis by stearate was associated with significantly increased levels of Hsp90β, peroxiredoxin-1, and 14-3-3γ in the membrane fraction of NES2Y cells and significantly decreased levels of annexin A2, annexin A4, and reticulocalbin-2. All these changes were significantly inhibited by oleate co-application.
No expression changes were detected after application of stearate together with oleate. Furthermore, the expression of reticulocalbin-2 was significantly decreased after stearate application also in the whole cell lysate.
CONCLUSIONS AND CLINICAL RELEVANCE: We identified several membrane-associated proteins that could be related to pro- and anti-apoptotic signaling initiated by fatty acids in human pancreatic β-cells. As far as we know, annexin A4, reticulocalbin-2, and 14-3-3γ represent novel molecules related to the effect of fatty acids on β-cell viability.