Sodium tanshinone IIA sulfonate protects ARPE-19 cells against oxidative stress by inhibiting autophagy and apoptosis

Abstract

Oxidative stress in retinal pigment epithelium (RPE) is considered to be a major contributor to the development and progression of age-related macular degeneration (AMD). Previous investigations have shown that sodium tanshinone IIA sulfonate (STS) can alleviate oxidative stress in haemorrhagic shock-induced organ damage and cigarette smoke-induced chronic obstructive pulmonary disease in mice. However, whether STS has a protective effect in ARPE-19 cells under oxidative stress and its exact mechanisms have not yet been fully elucidated. In the present study, we utilized H2O2 to establish an oxidative stress environment. Our findings show that STS activated the PI3K/AKT/mTOR pathway to inhibit autophagy and diminished the expression of the autophagic proteins Beclin 1, ATG3, ATG7 and ATG9 in ARPE-19 cells under oxidative stress. Detection of the intrinsic apoptosis-related factors BAX, mitochondrial membrane potential (MMP), caspase-9, caspase-3 and BCL-2, as well as the extrinsic apoptosis-related factors c-FLIP, v-FLIP and caspase-8, confirmed that STS inhibited the intrinsic and extrinsic apoptotic pathways, and attenuated apoptosis in ARPE-19 cells under oxidative stress conditions. These findings shed new light on the protective effects of STS in ARPE-19 cells and its mechanisms under oxidative stress to provide novel and promising therapeutic strategies for AMD.

The Anticancer Properties of Tanshinones and the Pharmacological Effects of Their Active Ingredients

“…In another study, Tan IIA induced autophagic cell death via activation of AMPK and ERK and inhibition of mTOR and rapamycin (mTOR), ribosomal protein S6 kinase (p70 S6K) in KBM-5 leukemia cells (Yun et al, 2013;Han et al, 2018). Moreover, it was pointed that the survival of osteosarcoma cell could be inhibited by Tan IIA through the PI3K/AKT signaling pathway, indicating that Tan IIA could effectively induce autophagy in human osteosarcoma cells (Yen et al, 2018).…”

Natural Drugs as a Treatment Strategy for Cardiovascular Disease through the Regulation of Oxidative Stress

“…An excessive reduction or increase in autophagic activity will affect the extent of oxidative stress-induced damage and atherosclerotic plaque development. Tanshinone II-A can also affect autophagic activity by regulating autophagy genes ATG and LC3, contributing to its antioxidant effects [ 190 ].…”

Autophagy and Age-Related Eye Diseases

“…In addition, Beclin 1, an autophagic protein, is important to nucleation of autophagy and also regulates apoptosis process. Its expression can be reduced by STS, which inhibits both autophagy and apoptosis in RPE cells [92]. In view of the results under different conditions, the mechanism of autophagy regulation in AMD at different stages deserves further investigation.…”

“…However, in some conditions, autophagy induced by oxidative stress can play an opposite role in RPE cells. For example, H 2 O 2 treatment triggers autophagy in ARPE-19 cells, which inhibits cell proliferation [92,93]. Erb-b2 receptor tyrosine-protein kinase 2 (ERBB2), a tyrosine kinase, belongs to the epidermal growth factor receptor (EGFR) family.…”