Ginsenoside Rg1 inhibits angiotensin II-induced podocyte autophagy via AMPK/mTOR/PI3K pathway

Cell Biol Int. 2016 Aug;40(8):917-25. doi: 10.1002/cbin.10634. Epub 2016 Jun 28.

Abstract

Recent researches have reported the extensive pharmacological activities of Ginsenoside Rg1 including antioxidant, anti-inflammatory, and anticancer properties. Furthermore Rg1 was also shown to protect various kinds of cells from self-digestion by its anti-autophagy activity. In previous studies, angiotensin II (Ang II), a key mediator of renin-angiotensin system, has been demonstrated to contribute to the progression of renal injury including abnormal autophagy. However, whether Rg1 can relieve Ang II-induced autophagy in podocyte as well as the underlying molecular mechanism remains to be elucidated. Here, we employed Ang II-treated podocyte as a model to investigate the effect of Rg1 on autophagy and the involved signal pathways. In the present study, we found that Ang II strongly promoted autophagy in immortalized mouse podocyte cells by observing the formation of autophagosomes and detecting the expression of autophagic marker, for example, LC3-II. Notably, compared to the Ang II-treated cells, treatment with Rg1 significantly inhibited the formation of autophagosomes and expression of autophagy-related proteins in Ang II pre-treated podocyte. Meanwhile, Rg1 downregulated the activity of AMPK and GSK-3β and upregulated the activity of P70S6K in Ang II-treated podocyte. In conclusion, these findings demonstrate that Ang II promotes autophagy in podocyte, and Rg1 effectively attenuates this process through AMPK/mTOR/PI3K pathway, suggesting that Rg1 may be beneficial to alleviate podocyte injury.

Keywords: Ang II; autophagy; ginsenoside Rg1; podocyte.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Angiotensin II / metabolism*
  • Animals
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Autophagy / drug effects*
  • Cell Line
  • Down-Regulation / drug effects
  • Ginsenosides / pharmacology*
  • Mice
  • Oxidative Stress / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation / drug effects
  • Podocytes / cytology
  • Podocytes / drug effects*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Antioxidants
  • Ginsenosides
  • Reactive Oxygen Species
  • Angiotensin II
  • mTOR protein, mouse
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • ginsenoside Rg1