Acetylcholine prevents angiotensin II-induced oxidative stress and apoptosis in H9c2 cells.

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.

• Authors: Jin-Jun Liu, Dong-Ling Li, Juan Zhou, Lei Sun, Ming Zhao, Shan-Shan Kong, You-Hua Wang, Xiao-Jiang Yu, Jun Zhou, Wei-Jin Zang
• Journal: Apoptosis : an international journal on programmed cell death (Apoptosis) Vol. 16 Issue 1 Pg. 94-103 (Jan 2011) ISSN: 1573-675X [Electronic] Netherlands
• PMID: 20963497 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Cardiotonic Agents
• Proto-Oncogene Proteins c-bcl-2
• Reactive Oxygen Species
• Receptor, Angiotensin, Type 1
• bcl-2-Associated X Protein
• Angiotensin II
• Atropine
• NADPH Oxidases
• p38 Mitogen-Activated Protein Kinases
• Caspase 3
• Acetylcholine

Topics

• Acetylcholine (metabolism, pharmacology)
• Angiotensin II (antagonists & inhibitors, pharmacology)
• Angiotensin II Type 1 Receptor Blockers
• Animals
• Apoptosis (drug effects)
• Atropine (pharmacology)
• Cardiotonic Agents (metabolism, pharmacology)
• Cardiovascular Diseases (prevention & control)
• Caspase 3 (genetics, metabolism)
• Cells, Cultured
• Gene Expression
• Myocytes, Cardiac (cytology, metabolism)
• NADPH Oxidases (antagonists & inhibitors, metabolism)
• Oxidative Stress (drug effects)
• Phosphorylation
• Proto-Oncogene Proteins c-bcl-2 (antagonists & inhibitors, genetics, metabolism)
• Rats
• Reactive Oxygen Species (metabolism)
• Receptor, Angiotensin, Type 1 (genetics, metabolism)
• bcl-2-Associated X Protein (genetics, metabolism)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, genetics, metabolism)