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Arch Oral Biol. 2014 May;59(5):513-23. doi: 10.1016/j.archoralbio.2014.02.015. Epub 2014 Mar 4.

Angiotensin II induces mitochondrial dysfunction and promotes apoptosis via JNK signalling pathway in primary mouse calvaria osteoblast.

Author information

1
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, P. R. China.
2
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, P. R. China. Electronic address: wtyloo@gmail.com.
3
UNIMED Medical Institute, Hong Kong, P. R. China; School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, P. R. China.
4
Faculty of Dentistry, The University of Hong Kong, Hong Kong, P. R. China.
5
Keenlink Dental Clinic, Hong Kong, P. R. China.
6
UNIMED Medical Institute, Hong Kong, P. R. China.

Abstract

OBJECTIVES:

This present study was designed to investigate the effects of Angiotensin II on mitochondrial functions, ROS generation and c-jun N-terminal kinases (JNK) signalling pathway-mediated cell apoptosis in mouse calvaria osteoblasts.

METHODS:

Calvaria osteoblast were isolated and cultured. The cells were separated into two groups-control and treated groups-where the latter was stimulated with angiotensin II (Ang II). Mitochondrial reactive oxygen species (ROS) and superoxide production were measured. Intracellular ATP levels were also detected. The cell proliferation rate was determined for the two groups. Protein production such as Anti-Bax, Bcl-2, COX IV and activation of c-jun N-terminal kinases signal (JNK) pathway was measured by enzyme-linked immunosorbent assay (ELISA) methods and Western blotting in this study.

RESULTS:

Ang II treated cells showed significantly higher levels of superoxide production compared to the control group (p<0.05). Conversely, Ang II induced inhibitory effects on mitochondrial respiratory enzyme complexes, cause membrane potential dissipation, ATP loss and promote ROS generation, cell apoptosis in cultured osteoblasts. In addition, JNK phosphorylations were involved in activating the mitochondria-dependent apoptotic pathway following Ang II stimulation, as pre-treatment of JNK-specific inhibitor SP600125 could rescue osteoblast cells from apoptosis by enhancing the anti-apoptotic protein Bcl-2 expressions, suppressing the translocation of Bax from cytosol into mitochondria, blocking cytochrome C release and caspase-3 activation.

CONCLUSIONS:

Ang II stimulates osteoblast apoptosis via suppression of the mitochondrial respiratory enzymes, membrane potential and cellular ATP productions. Clinical application with Ang II-stimulated osteoblast could be used for modelling or bone resorption in the oral region.

KEYWORDS:

Angiotensin II (Ang II); Apoptosis; JNK; Mitochondria; Reactive oxygen species (ROS)

[Indexed for MEDLINE]

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