Acetylcholine prevents angiotensin II-induced oxidative stress and apoptosis in H9c2 cells.
Apoptosis. 2011 Jan; 16(1):94-103.A

Abstract

Apoptosis of cardiomyocytes plays an important role in the development of cardiovascular diseases (CVD). Numerous studies have shown that generation of reactive oxygen species (ROS) induced by the renin-angiotensin system (RAS) is involved in this pathological process. Recent studies also suggested that acetylcholine (ACh) prevented the hypoxia-induced apoptosis of mouse ES cells by inhibiting the ROS production. However, whether ACh can inhibit the action of angiotensin II (Ang II) and subsequently prevent CVD development remains unclear. In this study, H9c2 cells were stimulated by 10(-6) M Ang II for 24 h with or without 10(-5) M ACh, 10(-5) M ACh + 10(-4) M atropine respectively. The results demonstrated that Ang II increased apoptosis index by fourfold (vs. the control group, P < 0.01), which were significantly diminished by ACh. However, the atropine (ACh receptor [AChR] inhibitor) treatment blocked the protective effect of ACh. Subsequently, Ang II significantly increases the expression and activity of NADPH oxidase so that ROS production is increased by sevenfold (vs. control group, P < 0.01). The activity and expression of caspase-3 along with the Bax/Bcl2 ratio and the levels of p38 mitogen activated protein kinase (MAPK) phosphorylation also appeared to follow a similar trend. Furthermore, we observed that ACh could reduce up-regulation of AT1 receptor expression induced by Ang II. However, all these effects of ACh were inhibited by atropine. In conclusion, ACh prevents Ang II-induced H9c2 cells apoptosis through down-regulation of the AT1 receptor and inhibition of ROS-mediated p38 MAPK activation as well as regulation of Bcl-2, Bax and caspase-3.

Links

Publisher Full Text

Authors+Show Affiliations

Liu JJ
Department of Pharmacology, Xi'an Jiaotong University, College of Medicine, Xi'an, People's Republic of China.
Li DL
No affiliation info available
Zhou J
No affiliation info available
Sun L
No affiliation info available
Zhao M
No affiliation info available
Kong SS
No affiliation info available
Wang YH
No affiliation info available
Yu XJ
No affiliation info available
Zhou J
No affiliation info available
Zang WJ
No affiliation info available

MeSH

AcetylcholineAngiotensin IIAngiotensin II Type 1 Receptor BlockersAnimalsApoptosisAtropineCardiotonic AgentsCardiovascular DiseasesCaspase 3Cells, CulturedGene ExpressionMyocytes, CardiacNADPH OxidasesOxidative StressPhosphorylationProto-Oncogene Proteins c-bcl-2RatsReactive Oxygen SpeciesReceptor, Angiotensin, Type 1bcl-2-Associated X Proteinp38 Mitogen-Activated Protein Kinases

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20963497