ArticleCell cycle (Georgetown, Tex.)2015
Acetylcholine ameliorates endoplasmic reticulum stress in endothelial cells after hypoxia/reoxygenation via M3 AChR-AMPK signaling.
Article in Cell cycle (Georgetown, Tex.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- The role of acetylcholine and its receptors in tumor immune regulation: mechanisms and potential therapeutic targets.Molecular cancer · 2025Review
- The Role of Muscarinic Acetylcholine Receptor MInternational journal of molecular sciences · 2024Review
- IRE1α: from the function to the potential therapeutic target in atherosclerosis.Molecular and cellular biochemistry · 2024Review
- Research progress on the natural products in the intervention of myocardial infarction.Frontiers in pharmacology · 2024Review
- Outcomes of hypothalamic oxytocin neuron-driven cardioprotection after acute myocardial infarction.Basic research in cardiology · 2023Article
- Cholinergic receptors play a role in the cardioprotective effects of anesthetic preconditioning: Roles of nitric oxide and the CaMKKβ/AMPK pathway.Experimental and therapeutic medicine · 2021Article
- Effect of endoplasmic reticulum stress on endothelial ischemia-reperfusion injury in humans.American journal of physiology. Regulatory, integrative and comparative physiology · 2020Article
- Integrative Analysis Revealing Human Heart-Specific Genes and Consolidating Heart-Related Phenotypes.Frontiers in genetics · 2020Article
- Pharmacological Modulation of Vagal Nerve Activity in Cardiovascular Diseases.Neuroscience bulletin · 2019Review
- Network pharmacology-based identification of major component ofBioscience reports · 2018Article
- Electroacupuncture brain protection during ischemic stroke: A role for the parasympathetic nervous system.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Article
- Vagal nerve stimulation improves mitochondrial dynamics via an MJournal of cellular and molecular medicine · 2017Article
- Hypothalamic kappa opioid receptor mediates both diet-induced and melanin concentrating hormone-induced liver damage through inflammation and endoplasmic reticulum stress.Hepatology (Baltimore, Md.) · 2016Article
- Inhibition of the mitochondrial unfolded protein response by acetylcholine alleviated hypoxia/reoxygenation-induced apoptosis of endothelial cells.Cell cycle (Georgetown, Tex.) · 2016Article
- C1q/TNF-Related Protein 9 Protects Diabetic Rat Heart against Ischemia Reperfusion Injury: Role of Endoplasmic Reticulum Stress.Oxidative medicine and cellular longevity · 2016Article
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7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress is associated with various cardiovascular diseases. However, its pathophysiological relevance and the underlying mechanisms in the context of hypoxia/reoxygenation (H/R) in endothelial cells are not fully understood. Previous findings have suggested that acetylcholine (ACh), the major vagal nerve neurotransmitter, protected against cardiomyocyte injury by activating AMP-activated protein kinase (AMPK). This study investigated the role of ER stress in endothelial cells during H/R and explored the beneficial effects of ACh. Our results showed that H/R triggered ER stress and apoptosis in endothelial cells, evidenced by the elevation of glucose-regulated protein 78, cleaved caspase-12 and C/EBP homologous protein expression. ACh significantly decreased ER stress and terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling positive cells and restored ER ultrastructural changes induced by H/R, possibly via protein kinase-like ER kinase and inositol-requiring kinase 1 pathways. Additionally, 4-diphenylacetoxy-N-methylpiperidine methiodide, a type-3 muscarinic ACh receptor (M3 AChR) inhibitor, abolished ACh-mediated increase in AMPK phosphorylation during H/R. Furthermore, M3 AChR or AMPK siRNA abrogated the ACh-elicited the attenuation of ER stress in endothelial cells, indicating that the salutary effects of ACh were likely mediated by M3 AChR-AMPK signaling. Overall, ACh activated AMPK through M3 AChR, thereby inhibited H/R-induced ER stress and apoptosis in endothelial cells. We have suggested for the first time that AMPK may function as an essential intermediate step between M3 AChR stimulation and inhibition of ER stress-associated apoptotic pathway during H/R, which may help to develop novel therapeutic approaches targeting ER stress to prevent or alleviate ischemia/reperfusion injury.
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