Genistein protects against ox-LDL-induced senescence through enhancing SIRT1/LKB1/AMPK-mediated autophagy flux in HUVECs

Mol Cell Biochem. 2019 May;455(1-2):127-134. doi: 10.1007/s11010-018-3476-8. Epub 2018 Nov 16.

Abstract

The anti-senescence activity of genistein is associated with inducing autophagy; however, the underlying mechanisms are not fully understood. In this study, human umbilical vein endothelial cells (HUVECs) were pretreated with genistein (1000 nM) for 30 min and then exposed to ox-LDL (50 mg/L) for another 12 h. The study found that genistein inhibited the ox-LDL-induced senescence (reducing the levels of P16 and P21 protein, and the activity of SA-β-gal); meanwhile, the effect of genistein was bound up with enhancing autophagic flux (increasing LC3-II, and decreasing the level of P62, p-mTOR and p-P70S6K). Moreover, SIRT1/LKB1/AMPK pathway was involved in genistein accelerating autophagic flux and mitigating senescence in HUVECs. The present study illustrated that genistein was a promising therapeutic agent to delay aging process and extend longevity.

Keywords: AMPK; Anti-senescence; Autophagy; Genistein; LKB1; SIRT1.

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • AMP-Activated Protein Kinases / metabolism*
  • Autophagy / drug effects*
  • Cellular Senescence / drug effects*
  • Genistein / pharmacology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lipoproteins, LDL / pharmacology*
  • Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction / drug effects*
  • Sirtuin 1 / metabolism*

Substances

  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • Genistein
  • Protein Serine-Threonine Kinases
  • STK11 protein, human
  • AMP-Activated Protein Kinase Kinases
  • AMP-Activated Protein Kinases
  • SIRT1 protein, human
  • Sirtuin 1