Ginsenoside Rg1 protects mouse podocytes from aldosterone-induced injury in vitro.

Abstract

AIM:

Aldosterone is elevated in many diseases such as hypertension, diabetic nephropathy and chronic kidney disease, etc. The aim of this study was to investigate the effects of aldosterone on intracellular ROS production and autophagy in podocytes in vitro, and to explore the possibility of ginsenoside Rg1 (Rg1) being used for protecting podocytes from aldosterone-induced injury.

METHODS:

MPC5 mouse podocyte cells were tested. Autophagosome and autophagic vacuole formation were examined under confocal microscopy with MDC and acridine orange staining, respectively. ROS were detected with flow cytometry. Malondialdehyde content and superoxide dismutase (T-SOD) activity were measured using commercial kits. The expression of LC3-II, beclin-1, SOD2 and catalase was measured by Western blotting.

RESULTS:

Treatment with aldosterone (10 nmol/L) significantly increased ROS generation and the expression of SOD2 and catalase in MPC5 cells. Furthermore, treatment with aldosterone significantly increased the conversion of LC3-I to LC3-II, beclin-1 expression and autophagosome formation. Co-treatment with rapamycin (1 ng/mL) or chloroquine (10 μmol/L) further increased aldosterone-induced autophagosome formation. Co-treatment with Rg1 (80 ng/mL) effectively relieved oxidative stress and increased T-SOD activity at the early stage and subsequently decreased autophagy in aldosterone-treated podocytes. Co-treatment with 3-MA (4 mmol/L) or NAC (50 mmol/L) exerted similar effects against aldosterone-induced autophagy in podocytes.

CONCLUSION:

Aldosterone enhances ROS generation and promotes autophagy in podocytes in vitro. Ginsenoside-Rg1 effectively relieves aldosterone-induced oxidative stress, thereby indirectly inhibiting aldosterone-induced podocyte autophagy.

• Authors: Nan Mao, Yuan Cheng, Xin-li Shi, Li Wang, Ji Wen, Qiong Zhang, Qiong-dan Hu, Jun-ming Fan
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 35 Issue 4 Pg. 513-22 (Apr 2014) ISSN: 1745-7254 [Electronic] United States
• PMID: 24632846 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Apoptosis Regulatory Proteins
• Beclin-1
• Becn1 protein, mouse
• Ginsenosides
• Map1lc3b protein, mouse
• Microtubule-Associated Proteins
• Reactive Oxygen Species
• Aldosterone
• Malondialdehyde
• Catalase
• Superoxide Dismutase
• superoxide dismutase 2
• ginsenoside Rg1

Topics

• Aldosterone (toxicity)
• Animals
• Antioxidants (pharmacology)
• Apoptosis Regulatory Proteins (metabolism)
• Autophagy (drug effects)
• Beclin-1
• Catalase (metabolism)
• Cell Line
• Cytoprotection
• Ginsenosides (pharmacology)
• Malondialdehyde (metabolism)
• Mice
• Microtubule-Associated Proteins (metabolism)
• Podocytes (drug effects, metabolism, ultrastructure)
• Reactive Oxygen Species (metabolism)
• Superoxide Dismutase (metabolism)