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Article: Plant Natural Product Formononetin Protects Rat Cardiomyocyte H9c2 Cells against Oxygen Glucose Deprivation and Reoxygenation via Inhibiting ROS Formation and Promoting GSK-3β Phosphorylation
Title | Plant Natural Product Formononetin Protects Rat Cardiomyocyte H9c2 Cells against Oxygen Glucose Deprivation and Reoxygenation via Inhibiting ROS Formation and Promoting GSK-3β Phosphorylation |
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Authors | |
Issue Date | 2016 |
Publisher | Hindawi Publishing Corporation. The Journal's web site is located at http://www.hindawi.com/journals/oximed/ |
Citation | Oxidative Medicine and Cellular Longevity, 2016, v. 2016, article no. 2060874 How to Cite? |
Abstract | The opening of mitochondrial permeability transition pore (mPTP) is a major cause of cell death in ischemia reperfusion injury. Based on our pilot experiments, plant natural product formononetin enhanced the survival of rat cardiomyocyte H9c2 cells during oxygen glucose deprivation (OGD) and reoxygenation. For mechanistic studies, we focused on two major cellular factors, namely, reactive oxygen species (ROS) and glycogen synthase kinase 3β (GSK-3β), in the regulation of mPTP opening. We found that formononetin suppressed the formation of ROS and superoxide in a concentration-dependent manner. Formononetin also rescued OGD/reoxygenation-induced loss of mitochondrial membrane integrity. Further studies suggested that formononetin induced Akt activation and GSK-3β (Ser9) phosphorylation, thereby reducing GSK-3β activity towards mPTP opening. PI3K and PKC inhibitors abolished the effects of formononetin on mPTP opening and GSK-3β phosphorylation. Immunoprecipitation experiments further revealed that formononetin increased the binding of phosphor-GSK-3β to adenine nucleotide translocase (ANT) while it disrupted the complex of ANT with cyclophilin D. Moreover, immunofluorescence revealed that phospho-GSK-3β (Ser9) was mainly deposited in the space between mitochondria and cell nucleus. Collectively, these results indicated that formononetin protected cardiomyocytes from OGD/reoxygenation injury via inhibiting ROS formation and promoting GSK-3β phosphorylation. |
Persistent Identifier | http://hdl.handle.net/10722/225612 |
ISSN | 2021 Impact Factor: 7.310 2023 SCImago Journal Rankings: 1.477 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Cheng, Y | - |
dc.contributor.author | Xia, Z | - |
dc.contributor.author | Han, Y | - |
dc.contributor.author | Rong, J | - |
dc.date.accessioned | 2016-05-20T08:09:21Z | - |
dc.date.available | 2016-05-20T08:09:21Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | Oxidative Medicine and Cellular Longevity, 2016, v. 2016, article no. 2060874 | - |
dc.identifier.issn | 1942-0900 | - |
dc.identifier.uri | http://hdl.handle.net/10722/225612 | - |
dc.description.abstract | The opening of mitochondrial permeability transition pore (mPTP) is a major cause of cell death in ischemia reperfusion injury. Based on our pilot experiments, plant natural product formononetin enhanced the survival of rat cardiomyocyte H9c2 cells during oxygen glucose deprivation (OGD) and reoxygenation. For mechanistic studies, we focused on two major cellular factors, namely, reactive oxygen species (ROS) and glycogen synthase kinase 3β (GSK-3β), in the regulation of mPTP opening. We found that formononetin suppressed the formation of ROS and superoxide in a concentration-dependent manner. Formononetin also rescued OGD/reoxygenation-induced loss of mitochondrial membrane integrity. Further studies suggested that formononetin induced Akt activation and GSK-3β (Ser9) phosphorylation, thereby reducing GSK-3β activity towards mPTP opening. PI3K and PKC inhibitors abolished the effects of formononetin on mPTP opening and GSK-3β phosphorylation. Immunoprecipitation experiments further revealed that formononetin increased the binding of phosphor-GSK-3β to adenine nucleotide translocase (ANT) while it disrupted the complex of ANT with cyclophilin D. Moreover, immunofluorescence revealed that phospho-GSK-3β (Ser9) was mainly deposited in the space between mitochondria and cell nucleus. Collectively, these results indicated that formononetin protected cardiomyocytes from OGD/reoxygenation injury via inhibiting ROS formation and promoting GSK-3β phosphorylation. | - |
dc.language | eng | - |
dc.publisher | Hindawi Publishing Corporation. The Journal's web site is located at http://www.hindawi.com/journals/oximed/ | - |
dc.relation.ispartof | Oxidative Medicine and Cellular Longevity | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Plant Natural Product Formononetin Protects Rat Cardiomyocyte H9c2 Cells against Oxygen Glucose Deprivation and Reoxygenation via Inhibiting ROS Formation and Promoting GSK-3β Phosphorylation | - |
dc.type | Article | - |
dc.identifier.email | Xia, Z: zyxia@hkucc.hku.hk | - |
dc.identifier.email | Rong, J: jrong@hku.hk | - |
dc.identifier.authority | Xia, Z=rp00532 | - |
dc.identifier.authority | Rong, J=rp00515 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1155/2016/2060874 | - |
dc.identifier.pmid | 27034732 | - |
dc.identifier.pmcid | PMC4806648 | - |
dc.identifier.scopus | eid_2-s2.0-84961324804 | - |
dc.identifier.hkuros | 257879 | - |
dc.identifier.volume | 2016 | - |
dc.identifier.isi | WOS:000373450300001 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 1942-0994 | - |