Plumbagin exerts protective effects in nucleus pulposus cells by attenuating hydrogen peroxide-induced oxidative stress, inflammation and apoptosis through NF-κB and Nrf-2

Total glucosides of peony (TGP) are used to treat rheumatoid arthritis and systemic lupus erythematosus. We explored the protective effects of TGP on cardiomyocyte oxidative stress and inflammation in the presence of hydrogen peroxide by focusing on mitochondrial dynamics and bioenergetics. Our study demonstrated that hydrogen peroxide significantly repressed cardiomyocyte viability and promoted cell apoptosis through induction of the mitochondrial death pathway. TGP treatment sustained cardiomyocyte viability, reduced cardiomyocyte apoptosis, and decreased inflammation and oxidative stress. Molecular investigation indicated that hydrogen peroxide caused mitochondrial dynamics disruption and bioenergetics reduction in cardiomyocytes, but this alteration could be normalized by TGP. We found that disruption of mitochondrial dynamics abolished the regulatory effects of TGP on mitochondrial bioenergetics; TGP modulated mitochondrial dynamics through the AMP-activated protein kinase (AMPK) pathway; and inhibition of AMPK alleviated the protective effects of TGP on mitochondria. Our results showed that TGP treatment reduces cardiomyocyte oxidative stress and inflammation in the presence of hydrogen peroxide by correcting mitochondrial dynamics and enhancing mitochondrial bioenergetics. Additionally, the regulatory effects of TGP on mitochondrial function seem to be mediated through the AMPK pathway. These findings are promising for myocardial injury in patients with rheumatoid arthritis and systemic lupus erythematosus.

Download Full-text

Liraglutide inhibits the apoptosis of human nucleus pulposus cells induced by high glucose through PI3K/Akt/caspase-3 signaling pathway

Bioscience Reports ◽

10.1042/bsr20190109 ◽

2019 ◽

Vol 39 (8) ◽

Cited By ~ 3

Author(s):

Yao Ming-yan ◽

Zhang Jing ◽

Guo Shu-qin ◽

Bai Xiao-liang ◽

Li Zhi-hong ◽

...

Keyword(s):

Signaling Pathway ◽

Nucleus Pulposus ◽

High Glucose ◽

Caspase 3 ◽

Maximum Effect ◽

Ros Generation ◽

Protective Effects ◽

Small Interfering Rnas ◽

Nucleus Pulposus Cells ◽

Pi3k Inhibitor Ly294002

Abstract Diabetes mellitus (DM) is a potential etiology of disc degeneration. Glucagon-like peptide-1 (GLP-1) is currently regarded as a powerful treatment option for type 2 diabetes. Apart from the beneficial effects on glycaemic control, GLP-1 has been reported to exert functions in a variety of tissues on modulation of cell proliferation, differentiation, and apoptosis. However, little is known regarding the effects of GLP-1 on nucleus pulposus cells (NPCs). In the present study, we investigated the effects of liraglutide (LIR), a long-lasting GLP-1 analogue, on apoptosis of human NPCs and the underlying mechanisms involved. We confirmed the presence of GLP-1 receptor (GLP-1R) in NPCs. Our data demonstrated that liraglutide inhibited the apoptosis of NPCs induced by high glucose (HG), as detected by Annexin V/Propidium Iodide (PI) and ELISA assays. Moreover, liraglutide down-regulated caspase-3 activity at intermediate concentration (100 nM) for maximum effect. Further analysis suggested that liraglutide suppressed reactive oxygen species (ROS) generation and stimulated the phosphorylation of Akt under HG condition. Pretreatment of cells with the Phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (LY) and small interfering RNAs (siRNAs) GLP-1R abrogated the liraglutide-induced activation of Akt and the protective effects on NPCs’ apoptosis. In conclusion, liraglutide could directly protect NPCs against HG-induced apoptosis by inhibiting oxidative stress and activate the PI3K/Akt/caspase-3 signaling pathway via GLP-1R.

Download Full-text