Sulforaphane protects human umbilical vein cells against lipotoxicity by stimulating autophagy via an AMPK-mediated pathway

Abstract

The protective role of sulforaphane (SFN) against saturated fatty acid (SFA)-induced lipotoxicity in human umbilical vein endothelium cell was determined. SFN protected endothelium cells against SFA-induced cell death. This protective activity was Nrf2-independent because silencing Nrf2 did not block the protective action of SFN. Subsequent studies revealed that SFN-induced autophagy contributed to the protective role. Incubation of the cells with autophagy inhibitors significantly blocked the protection by SFN. In addition, SFN significantly enhanced the formation of LC3-II and increased autophagic flux. Mechanistic study revealed that SFN significantly stimulated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and reduced the phosphorylation of the mammalian target of rapamycin (mTOR). Moreover, knocking-down AMPK significantly blocked SFN-induced autophagy and inhibited its protective role against lipotoxicity. This finding provides novel data demonstrating that SFN protects endothelial cells from SFA-induced lipotoxicity through activating autophagy via an AMPK/mTOR involved pathway.

Keywords

• Sulforaphane
• Saturated fatty acid
• Autophagy
• Lipotoxicity
• Endothelial cell