Publications by authors named "Peng-Zhou Hang"

14 Publications

  • Page 1 of 1

The regulatory role of the BDNF/TrkB pathway in organ and tissue fibrosis.

Histol Histopathol 2021 Jul 30:18368. Epub 2021 Jul 30.

Department of Pharmacy, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, China.

Fibrosis across diverse organ systems is one of the leading causes of morbidity and mortality by inducing progressive architectural remodeling and organ dysfunction. Brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase receptor B (TrkB) play crucial roles in regulating neural survival, development, function and plasticity in the central and the peripheral nervous system. Previous studies demonstrated that the BDNF/TrkB pathway is widely distributed in different cell types such as neuron, epithelial cell, hepatocyte, and cardiomyocyte. Recently, there is increasing recognition that BDNF and TrkB are also expressed in fibroblasts in different organs. Moreover, growing evidence was obtained regarding the functional roles of BDNF/TrkB signaling in organ and tissue fibrosis. Thus, this review summarizes the basic molecular characteristics of the BDNF/TrkB cascade and the findings of the crucial roles and therapeutic value in organ and tissue fibrosis including pulmonary fibrosis, hepatic fibrosis, renal fibrosis, cardiac fibrosis, bladder fibrosis and skin fibrosis. Small molecule BDNF mimetic and BDNF-related non-coding RNAs are also discussed for developing new therapeutic approaches for fibrotic disorders.
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http://dx.doi.org/10.14670/HH-18-368DOI Listing
July 2021

MicroRNA-98 ameliorates doxorubicin-induced cardiotoxicity via regulating caspase-8 dependent Fas/RIP3 pathway.

Environ Toxicol Pharmacol 2021 Jul 19;85:103624. Epub 2021 Feb 19.

Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research), Heilongjiang Province, Harbin, 150086, China; Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, 150081, China; State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, 999078, China. Electronic address:

Cardiotoxicity is one of the primary limitations in the clinical use of the anticancer drug doxorubicin (DOX). However, the role of microRNAs (miRNAs) in DOX-induced cardiomyocyte death has not yet been covered. To investigate this, we observed a significant increase in miR-98 expression in neonatal rat ventricular myocytes after DOX treatment, and MTT, LIVE/Dead and Viability/Cytotoxicity staining showed that miR-98 mimic inhibited DOX-induced cell death. This was also confirmed by Flow cytometry and Annexin V-FITC/PI staining. Interestingly, the protein expression of caspase-8 was upregulated by miR-98 mimics during this process, whereas Fas and RIP3 were downregulated. In addition, the effect of miR-98 against the expression of Fas and RIP3 were restored by the specific caspase-8 inhibitor Z-IETD-FMK. Thus, we demonstrate that miR-98 protects cardiomyocytes from DOX-induced injury by regulating the caspase-8-dependent Fas/RIP3 pathway. Our findings enhance understanding of the therapeutic role of miRNAs in the treatment of DOX-induced cardiotoxicity.
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http://dx.doi.org/10.1016/j.etap.2021.103624DOI Listing
July 2021

Letter by Hang and Zhao Regarding Article, "Cardiac Overexpression of PDE4B Blunts β-Adrenergic Response and Maladaptive Remodeling in Heart Failure".

Circulation 2021 Jan 25;143(4):e24-e25. Epub 2021 Jan 25.

Medical Research Center (J.Z.), Clinical Medical College, Yangzhou University; Northern Jiangsu People's Hospital, Yangzhou, China.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050998DOI Listing
January 2021

The Emerging Role of BDNF/TrkB Signaling in Cardiovascular Diseases.

Life (Basel) 2021 Jan 19;11(1). Epub 2021 Jan 19.

Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research), Harbin 150086, China.

Brain-derived neurotrophic factor (BDNF) is one of the most abundantneurotrophins in the central nervous system. Numerous studies suggestthat BDNF has extensive roles by binding to its specific receptor, tropomyosin-related kinase receptor B (TrkB), and thereby triggering downstream signaling pathways. Recently, growing evidence highlightsthat the BDNF/TrkB pathway is expressed in the cardiovascular system andclosely associated with the development and outcome of cardiovascular diseases (CVD), including coronary artery disease, heart failure, cardiomyopathy, hypertension, and metabolic diseases. Furthermore, circulating BDNF has also been revealed as a new potential biomarker for both diagnosis and prognosis of CVD. In this review, we discuss the current evidence of the emerging role of BDNF/TrkBsignalingand address the challenges that remain in translating these discoveries to novel therapeutic strategies for CVD.
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http://dx.doi.org/10.3390/life11010070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833389PMC
January 2021

Aloe-emodin exerts cholesterol-lowering effects by inhibiting proprotein convertase subtilisin/kexin type 9 in hyperlipidemic rats.

Acta Pharmacol Sin 2020 Aug 18;41(8):1085-1092. Epub 2020 Mar 18.

Institute of Clinical Pharmacology, The Second Affiliated Hospital of Harbin Medical University (University Key Laboratory of Drug Research, Heilongjiang Province), Harbin, 150086, China.

Hyperlipidemia (HPL) characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor (LDLR) in the lysosome of hepatocytes. Aloe-emodin (AE) is one of potentially bioactive components of Chinese traditional medicine Daming capsule. In this study we evaluated the HPL-lowering efficacy of AE in both in vivo and in vitro HPL models. High-fat diet-induced rats were treated with AE (100 mg/kg per day, ig) for 6 weeks. We found that AE administration significantly decreased the levels of total cholesterol (TC) and LDL in the serum and liver tissues. Moreover, AE administration ameliorated HPL-induced hepatic lipid aggregation. But AE administration did not significantly inhibit HMG-CoA reductase activity in the liver of HPL rats. A cellular model of HPL was established in human hepatoma (HepG2) cells treated with cholesterol (20 μg/mL) and 25-hydroxycholesterol (2 μg/mL), which exhibited markedly elevated cholesterol levels. The increased cholesterol levels could be reversed by subsequent treatment with AE (30 μM). In both the in vivo and in vitro HPL models, we revealed that AE selectively suppressed the sterol-regulatory element-binding protein-2 (SREBP-2) and hepatocyte nuclear factor (HNF)1α-mediated PCSK9 signaling, which in turn upregulated LDL receptor (LDLR) and promoted LDL uptake. This study demonstrates that AE reduces cholesterol content in HPL rats by inhibiting the hepatic PCSK9/LDLR pathway.
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http://dx.doi.org/10.1038/s41401-020-0392-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470781PMC
August 2020

Brain-derived neurotrophic factor mimetic, 7,8-dihydroxyflavone, protects against myocardial ischemia by rebalancing optic atrophy 1 processing.

Free Radic Biol Med 2019 12 28;145:187-197. Epub 2019 Sep 28.

Institute of Clinical Pharmacology, The Second Affiliated Hospital (The University Key Laboratory of Drug Research, Heilongjiang Province), Department of Clinical Pharmacology, College of Pharmacy, Harbin Medical University, Harbin, 150086, China; State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China. Electronic address:

Brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway is associated with ischemic heart diseases (IHD). 7,8-dihydroxyflavone (7,8-DHF), BDNF mimetic, is a potent agonist of TrkB. We aimed to investigate the effects and the underlying mechanisms of 7,8-DHF on cardiac ischemia. Myocardial ischemic mouse model was induced by ligation of left anterior descending coronary artery. 7,8-DHF (5 mg/kg) was administered intraperitoneally two days after ischemia for four weeks. Echocardiography, HE staining and transmission electron microscope were used to examine the function, histology and ultrastructure of the heart. H9c2 cells were treated with hydrogen peroxide (HO), 7,8-DHF or TrkB inhibitor ANA-12. The effects of 7,8-DHF on cell viability, mitochondrial membrane potential (MMP) and mitochondrial superoxide generation were examined. Furthermore, mitochondrial fission and protein expression of mitochondrial dynamics (Mfn2 [mitofusin 2], OPA1 [optic atrophy 1], Drp1 [dynamin-related protein 1] and Fis-1 [fission 1]) was detected by mitotracker green staining and western blot, respectively. 7,8-DHF attenuated cardiac dysfunction and cardiomyocyte abnormality of myocardial ischemic mice. Moreover, 7,8-DHF increased cell viability and reduced cell death accompanied by improving MMP, inhibiting mitochondrial superoxide and preventing excessive mitochondrial fission of HO-treated H9c2 cells. The cytoprotective effects of 7,8-DHF were antagonized by ANA-12. Mechanistically, 7,8-DHF repressed OMA1-dependent conversion of L-OPA1 into S-OPA1, which was abolished by Akt inhibitor. In conclusion, 7,8-DHF protects against cardiac ischemic injury by inhibiting the proteolytic cleavage of OPA1. These findings provide a novel pharmacological effect of 7,8-DHF on mitochondrial dynamics and a new potential target for IHD.
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http://dx.doi.org/10.1016/j.freeradbiomed.2019.09.033DOI Listing
December 2019

MicroRNA-132 regulates total protein of Nav1.1 and Nav1.2 in the hippocampus and cortex of rat with chronic cerebral hypoperfusion.

Behav Brain Res 2019 07 15;366:118-125. Epub 2019 Mar 15.

Department of Pharmacology, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang Province, 150081, China. Electronic address:

Nav1.1 and Nav1.2 are the voltage-gated sodium channel alpha subunit1 and 2, encoded by the genes of SCN1A and SCN2A. Previous studies have shown that chronic cerebral hypoperfusion (CCH) could induce neuropathological and cognitive impairment and increased total Nav1.1 and Nav1.2protein levels, yet the detailed mechanisms are not fully understood. MicroRNAs (miRNAs) are a class of small, non-coding RNAs that are involved in the regulation of dementia. miR-132 is known to play a key role in neurodegenerative disease. Here, we determined that miR-132 regulates Nav1.1 and Nav1.2 under CCH state. In this study, the expression of miR-132 was decreased in both the hippocampus and cortex of ratsfollowing CCH generated by bilateral common carotid artery occlusion (2VO). Lentiviral-mediated overexpression of miR-132 ameliorated dementia vulnerability induced by 2VO. At the molecular level, miR-132 repressed the increased protein expression of Nav1.1 and Nav1.2 in both the hippocampus and cortex induced by 2VO. MiR-132 suppressed, while AMO-miR-132 enhanced, the level of Nav1.1 and Nav1.2 in primary cultured neonatal rat neurons (NRNs) detected by both western blot analysis and immunofluorescence analysis. Results obtained by dual luciferase assay showed that overexpression of miR-132 inhibited the expression of Nav1.1 and Nav1.2 in human embryonic kidney 293 (HEK293T) cells. Additionally, binding-site mutation failed to influence Nav1.1 and Nav1.2, indicating that Nav1.1 and Nav1.2 are potential targets for miR-132. Taken together, our findings demonstrated that miR-132 protects against CCH-induced learning and memory impairments by down-regulating the expression of Nav1.1 and Nav1.2, and SCN1A and SCN2A are the target genes of miR-132.
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http://dx.doi.org/10.1016/j.bbr.2019.03.026DOI Listing
July 2019

Combination of microRNA-21 and microRNA-146a Attenuates Cardiac Dysfunction and Apoptosis During Acute Myocardial Infarction in Mice.

Mol Ther Nucleic Acids 2016 Mar 15;5:e296. Epub 2016 Mar 15.

Institute of Clinical Pharmacology of the Second Affiliated Hospital, Harbin Medical University, Harbin, China.

Recent studies have revealed the cytoprotective roles of microRNAs (miRNAs) miR-21 and miR-146a against ischemic cardiac injuries. While these studies investigated each of these miRNAs as an independent individual factor, our previous study has suggested the possible interaction between these two miRNAs. The present study was designed to investigate this possibility by evaluating the effects of miR-21 and miR-146a combination on cardiac ischemic injuries and the underlying mechanisms. MiR-21 and miR-146a synergistically decreased apoptosis under ischemia/hypoxic conditions in cardiomyocytes compared with either miR-21 or miR-146a alone. Mice coinjected with agomiR-21 and agomiR-146a had decreased infarct size, increased ejection fraction (EF), and fractional shortening (FS). These effects were greater than those induced by either of the two agomiRs. Furthermore, greater decreases in p38 mitogen-associated protein kinase phosphorylation (p-p38 MAPK) were observed with miR-21: miR-146a combination as compared to application of either of the miRNAs. These data suggest that combination of miR-21 and miR-146a has a greater protective effect against cardiac ischemia/hypoxia-induced apoptosis as compared to these miRNAs applied individually. This synergistic action is mediated by enhanced potency of inhibition of cardiomyocyte apoptosis by the miR-21-PTEN/AKT-p-p38-caspase-3 and miR-146a-TRAF6-p-p38-caspase-3 signal pathways.
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http://dx.doi.org/10.1038/mtna.2016.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5014454PMC
March 2016

Fenofibrate inhibits atrial metabolic remodelling in atrial fibrillation through PPAR-α/sirtuin 1/PGC-1α pathway.

Br J Pharmacol 2016 Mar 18;173(6):1095-109. Epub 2016 Feb 18.

Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.

Background And Purpose: Atrial metabolic remodelling is critical for the process of atrial fibrillation (AF). The PPAR-α/sirtuin 1 /PPAR co-activator α (PGC-1α) pathway plays an important role in maintaining energy metabolism. However, the effect of the PPAR-α agonist fenofibrate on AF is unclear. Therefore, the aim of this study was to determine the effect of fenofibrate on atrial metabolic remodelling in AF and explore its possible mechanisms of action.

Experimental Approach: The expression of metabolic proteins was examined in the left atria of AF patients. Thirty-two rabbits were divided into sham, AF (pacing with 600 beats·min(-1) for 1 week), fenofibrate treated (pretreated with fenofibrate before pacing) and fenofibrate alone treated (for 2 weeks) groups. HL-1 cells were subjected to rapid pacing in the presence or absence of fenofibrate, the PPAR-α antagonist GW6471 or sirtuin 1-specific inhibitor EX527. Metabolic factors, circulating biochemical metabolites, atrial electrophysiology, adenine nucleotide levels and accumulation of glycogen and lipid droplets were assessed.

Key Results: The PPAR-α/sirtuin 1/PGC-1α pathway was significantly inhibited in AF patients and in the rabbit/HL-1 cell models, resulting in a reduction of key downstream metabolic factors; this effect was significantly restored by fenofibrate. Fenofibrate prevented the alterations in circulating biochemical metabolites, reduced the level of adenine nucleotides and accumulation of glycogen and lipid droplets, reversed the shortened atrial effective refractory period and increased risk of AF.

Conclusion And Implications: Fenofibrate inhibited atrial metabolic remodelling in AF by regulating the PPAR-α/sirtuin 1/PGC-1α pathway. The present study may provide a novel therapeutic strategy for AF.
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http://dx.doi.org/10.1111/bph.13438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341245PMC
March 2016

Vitexin protects against cardiac hypertrophy via inhibiting calcineurin and CaMKII signaling pathways.

Naunyn Schmiedebergs Arch Pharmacol 2013 Aug 28;386(8):747-55. Epub 2013 Apr 28.

Institute of Clinical Pharmacology, The Second Affiliated Hospital, Harbin Medical University, Harbin, 150086, Heilongjiang, People's Republic of China.

Vitexin is a flavone glycoside isolated from the leaf of Crataeguspinnatifida Bunge, the utility of which has been demonstrated in several cardiovascular diseases. However, its role in cardiac hypertrophy remains unclear. In the present study, we aimed to determine whether vitexin prevents cardiac hypertrophy induced by isoproterenol (ISO) in cultured neonatal rat ventricular myocytes in vitro and pressure overload-induced cardiac hypertrophy in mice in vivo. The results revealed that vitexin (10, 30, and 100 μM) dose-dependently attenuated cardiac hypertrophy induced by ISO in vitro. Furthermore, vitexin (3, 10, and 30 mg kg(-1)) prevented cardiac hypertrophy induced by transverse aortic constriction as assessed by heart weight/body weight, left ventricular weight/body weight and lung weight/body weight ratios, cardiomyocyte cross-sectional area, echocardiographic parameters, and gene expression of hypertrophic markers. Further investigation demonstrated that vitexin inhibited the increment of the resting intracellular free calcium induced by ISO. Vitexin also inhibited the expression of calcium downstream effectors calcineurin-NFATc3 and phosphorylated calmodulin kinase II (CaMKII) both in vitro and in vivo. Taken together, our results indicate that vitexin has the potential to protect against cardiac hypertrophy through Ca2+-mediated calcineurin-NFATc3 and CaMKII signaling pathways.
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http://dx.doi.org/10.1007/s00210-013-0873-0DOI Listing
August 2013

Verapamil reverses cardiac iron overload in streptozocin-induced diabetic rats.

Naunyn Schmiedebergs Arch Pharmacol 2013 Jul 7;386(7):645-50. Epub 2013 Apr 7.

Key Laboratory of Drug Research, Heilongjiang Higher Education Institutions, Harbin Medical University, Harbin, People's Republic of China.

Accumulating evidence shows that iron overload is a new risk factor for diabetes mellitus. L-type Ca(2+) channel (LTCC) has been identified as an important mediator for ferrous iron uptake into cardiomyocytes. In this study, we aimed to examine the effects of verapamil, the LTCC blocker, on myocardial iron metabolism in diabetic rats. Diabetes was induced by intraperitoneal injection of streptozocin after intragastric administration of fat emulsion, and then treated by verapamil (5 mg · kg(-1) · day(-1)) for 1 week. The results showed that verapamil did not alter the blood glucose level of diabetic rats. However, elevated levels of superoxide dismutase, malonaldehyde, and serum ferritin in diabetic rats were decreased significantly by verapamil treatment. Moreover, serum, myocardial, and urine iron were elevated remarkably along with a decrease of hepatic iron in diabetic rats. After verapamil administration, serum and myocardial iron in diabetic rats were reduced significantly but urine and hepatic iron were increased. Furthermore, confocal microscopy demonstrated that intracellular-free iron concentration was elevated dramatically in cardiomyocytes of diabetic rats, which was markedly attenuated after verapamil treatment. In summary, our data demonstrated that verapamil prevented myocardial iron overload by inhibiting intracellular iron accumulation in diabetic cardiomyocytes.
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http://dx.doi.org/10.1007/s00210-013-0863-2DOI Listing
July 2013

Choline inhibits angiotensin II-induced cardiac hypertrophy by intracellular calcium signal and p38 MAPK pathway.

Naunyn Schmiedebergs Arch Pharmacol 2012 Aug 9;385(8):823-31. Epub 2012 May 9.

Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, Heilongjiang 150081, People's Republic of China.

Choline, an agonist of M(3) muscarinic acetylcholine receptors, is a precursor and metabolite of acetylcholine and is also a functional modulator of cellular membrane. However, the effect of choline on cardiac hypertrophy is not fully understood. The present study was therefore designed to explore whether choline could prevent cardiac hypertrophy induced by angiotensin II (Ang II) and clarify its potential mechanisms. Cardiac hypertrophy was induced by 0.6 mg kg(-1) day(-1) Ang II for 2 weeks in the presence or absence of choline pretreatment, while cardiomyocyte hypertrophy was induced by Ang II 0.1 μM for 48 h. We found that choline pretreatment attenuated the increment cell size of cardiomyocytes induced by Ang II both in vivo and in vitro. The high ANP and β-MHC levels induced by Ang II were also reversed by choline in cardiomyocytes. Meanwhile, choline pretreatment prevented the augment of reactive oxygen species (ROS) and intracellular calcium concentration in Ang II-treated cardiomyocytes. Furthermore, the upregulated phospho-p38 mitogen-activated protein kinase (MAPK) and calcineurin levels by Ang II in ventricular myocytes were attenuated by choline. In conclusion, choline prevents Ang II-induced cardiac hypertrophy through inhibition of ROS-mediated p38 MAPK activation as well as regulation of Ca(2+)-mediated calcineurin signal transduction pathway. Our results provide new insights into the pharmacological role of choline in cardiovascular diseases.
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http://dx.doi.org/10.1007/s00210-012-0740-4DOI Listing
August 2012

Reciprocal regulation between M3 muscarinic acetylcholine receptor and protein kinase C-epsilon in ventricular myocytes during myocardial ischemia in rats.

Naunyn Schmiedebergs Arch Pharmacol 2009 Nov 15;380(5):443-50. Epub 2009 Aug 15.

Institute of Clinical Pharmacology of Second Hospital, Harbin Medical University, Key Laboratory of Heilongjiang Province, Baojian Road 157, Nangang District, Harbin, Heilongjiang Province, 150081, People's Republic of China.

We have studied the association between M(3) muscarinic acetylcholine receptors (M(3)-mAChR) and protein kinase C-epsilon (PKC-epsilon) during ischemic myocardial injury using Western blot analysis and immunoprecipitation technique. Myocardial ischemia (MI) induced PKC-epsilon translocation from cytosolic to membrane fractions. This translocation participated in the phosphorylation of M(3)-mAChR in membrane fractions, which could be abolished by the inhibitor of PKC, chelerythrine chloride. On the other hand, M(3)-mAChR could also regulate the expression of PKC-epsilon in ischemic myocardium. Choline (choline chloride, an M(3) receptor agonist, administered at 15 min before occlusion) strengthened the association between PKC-epsilon and M(3)-mAChR. However, blockade of M(3)-mAChR by 4-diphenylacetoxy-N-methylpiperidine methiodide (an M(3) receptor antagonist, administered at 20 min before occlusion) completely inhibited the effect of choline on the expression of PKC-epsilon. We conclude that the translocation of PKC-epsilon is required for the phosphorylation of M(3)-mAChR; moreover, increased PKC-epsilon activity is associated with M(3)-mAChR during MI. This reciprocal regulation is likely to play a role in heart signal transduction during ischemia between ventricular myocytes.
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http://dx.doi.org/10.1007/s00210-009-0444-6DOI Listing
November 2009

M3 muscarinic acetylcholine receptor is associated with beta-catenin in ventricular myocytes during myocardial infarction in the rat.

Clin Exp Pharmacol Physiol 2009 Oct 26;36(10):995-1001. Epub 2009 Mar 26.

Institute of Clinical Pharmacology of Second Hospital, Harbin Medical University, Harbin, PR China.

1. The present study was designed to investigate whether the M(3) muscarinic acetylcholine receptors (mAChR) is associated with beta-catenin in the ventricular myocardium during ischaemic myocardial injury and to determine the possible mechanism/s involved. 2. Rat hearts were subjected to coronary artery ligation for 1 and 6 h or 1 month to establish a myocardial ischaemia (MI) model. In the acute MI model, 16 rats were randomized into four groups: (i) control; (ii) ischaemia (rats were subjected to 20 min coronary occlusion); (iii) choline (10 mg/kg, i.v., choline chloride, an M(3) receptor agonist, was administered 15 min before occlusion); and (iv) 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; 0.12 mg/kg 4-DAMP, an M(3) receptor antagonist, was administered 20 min before occlusion, followed 5 min later by 10 mg/kg, i.v., choline chloride). Immunochemistry, western blot analysis and immunoprecipitation were used to determine the expression and localization of beta-catenin and the M(3) mAChR. 3. Myocardial ischaemia caused a time-dependent increase in the expression of beta-catenin. Moreover, a physical association was found between beta-catenin and the M(3) mAChR in intercalated discs. This association was enhanced by prolonged ischaemia. Administration of choline before ischaemia not only increased beta-catenin expression, but also strengthened the association between beta-catenin and the M(3) mAChR. However, blockade of M(3) mAChR by 4-DAMP completely inhibited the effect of choline on the expression of beta-catenin. In addition, MI increased phosphorylation of the M(3) mAChR. 4. The results indicate that increased beta-catenin activity is associated with M(3) mAChR during MI. This association is likely to play a role in heart signal transduction during ischaemia between neighbouring ventricular myocardiocum.
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http://dx.doi.org/10.1111/j.1440-1681.2009.05176.xDOI Listing
October 2009
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