Protective effect of carbachol postconditioning on hypoxia/reoxygenation-induced injury in human gastric epithelial cells
Autor: | Su-Juan Fei, Hong-Xia Han, Sheng-Ping Zhu, Zhifeng Gao, Zhang-Bo Liu, Jun Yang, Qiu-Ju Dong, Shihui Wang, Jian-Fu Zhang |
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Rok vydání: | 2015 |
Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Carbachol Cell Survival MAP Kinase Signaling System Calcitonin Gene-Related Peptide Apoptosis Pharmacology Biology Calcitonin gene-related peptide Muscarinic Agonists General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences 0302 clinical medicine Internal medicine Muscarinic acetylcholine receptor medicine Extracellular Gastric mucosa Humans Viability assay General Pharmacology Toxicology and Pharmaceutics Hypoxia Ischemic Postconditioning Stomach Epithelial Cells General Medicine Receptors Muscarinic Endocrinology medicine.anatomical_structure Gastric Mucosa 030220 oncology & carcinogenesis 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Life sciences. 144 |
ISSN: | 1879-0631 |
Popis: | Aims We investigated the protective effects of carbachol postconditioning (CAR-P) on acute gastric mucosal injury induced by hypoxia/reoxygenation (H/R) and its possible mechanisms. Main methods Cell viability was detected by methyl thiazolyl tetrazolium (MTT). The apoptotic cells were examined by Hoechst 33258 staining. Flow cytometric analysis, lactate dehydrogenate (LDH) release assay, immunocytochemistry, and western blotting were used to investigate the effects of CAR-P on acute gastric mucosal injury induced by H/R. The model of H/R was established by hypoxia induction(94% N 2 + 1% O 2 + 5% CO 2 for 2 h) and reoxygenation (normoxic condition for 4 h, 8 h and 16 h). Key findings Our study observed the protective effect of carbachol postconditioning on H/R-induced injury in human gastric epithelial cell lines (hGES-1) cells, which is achieved by direct activation of vanilloid receptor subtype 1 (VR1) and production of calcitonin gene-related peptide (CGRP), and in the inhibition of cell apoptosis. In the study, we demonstrate that CAR-P has protective effects on the H/R-induced injury in hGES-1 cells, and these effects are associated with cholinergic muscarinic receptors (CMR), VR1, and extracellular signal-regulated kinase (ERK) signaling pathway. Significance Our findings might provide a new and improved understanding of CAR-P function and an effective treatment strategy for acute gastric mucosal injury induced by H/R. |
Databáze: | OpenAIRE |
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