title: Penehyclidine hydrochloride prevents anoxia/reoxygenation injury and induces H9c2 cardiomyocyte apoptosis via a mitochondrial pathway.
abstract: Penehyclidine hydrochloride (PHC) is an anticholinergic drug that has been widely used in the clinic for years, evaluating for anesthetic premedication, anti-muscarinic, or improving microcirculation. However, very little is known about its protective effects against anoxia/reoxygenation (A/R) injury in myocardiocytes. The aim of our study was to investigate the protective effects of PHC pretreatment on A/R injury, as well as the underlying mechanisms involved. To investigate apoptosis, we used the cell viability assay, Annexin-V/PI assay, and lactate dehydrogenase (LDH) and creatine kinase (CK) activity measurements. Intracellular Ca2+concentrations, reactive oxygen species (ROS), malonaldehyde (MDA), superoxide dismutase (SOD), and mitochondrial membrane potential were also measured. To analyze the molecular mechanisms, mitochondrial permeability transition pore (MPTP) activity and mRNA expressions of Bcl-2, Bax, cytochrome C (Cyt-C), caspase-3, and voltage-dependent anion channel (VDAC) were assessed. Pretreatment with PHC significantly increased cell viability and decreased the percentage of apoptotic cells, as well as LDH and CK activity, which was accompanied by a reduction in intracellular Ca2+concentration, ROS, and MDA, as well as an increase in SOD levels. PHC pretreatment also restored mitochondrial membrane potential. Moreover, pre-incubation with PHC significantly attenuated MPTP activity and mRNA expressions of Bax, Cyt-C, caspase-3, and VDAC. Our results showed that PHC pretreatment protected H9c2 cells against A/R injury by modulating the mitochondrial apoptosis pathway.
authors.affiliation: Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, PR China.
authors.forename: Zhaoqi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, PR China.
authors.forename: Duomao
authors.initials: D
authors.lastname: Lin
authors.affiliation: Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, PR China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
authors.affiliation: Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, PR China.
authors.forename: Hongbao
authors.initials: H
authors.lastname: Tan
authors.affiliation: Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, PR China. Electronic address: majuntongxun@sohu.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003402:Creatine Kinase / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D011812:Quinuclidines / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D011812:Quinuclidines; C486140:penehyclidine; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D010100:Oxygen; D002118:Calcium
keywords: Anoxia/reoxygenation injury; Mitochondrial pathway; Penehyclidine hydrochloride