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Conference Paper: Overexpression of miR-503-5p exacerbates hypoxia/reoxygenation injury in H9C2 cardiomyocytes
Title | Overexpression of miR-503-5p exacerbates hypoxia/reoxygenation injury in H9C2 cardiomyocytes |
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Authors | |
Issue Date | 2019 |
Publisher | Federation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/ |
Citation | Experimental Biology 2019 Meeting, Orlando, USA, 6-9 April 2019. In The FASEB Journal, 2019, v. 33 n. 1, Suppl., abstract no. 676.4 How to Cite? |
Abstract | Acute myocardial infarction (MI) is a leading cause of death worldwide, and the most effective therapy for reducing acute myocardial ischemic injury is myocardial reperfusion, while reperfusion itself can lead to further cardiomyocyte death, called ischemia/reperfusion injury (IRI). A number of microRNAs have been shown to be involved in IRI, however, the role of miR-503-5p, which is implicated in cancers, diabetes mellitus or pulmonary arterial hypertension, remains unknown in myocardial IRI. This study was aimed to investigate the effects of miR-503-5p in myocardial IRI. Cardiac miR-503-5p expression was measured in mice subjected to myocardial IRI achieved by occlusion of left anterior descending artery for 30 minutes followed by reperfusion for 2 hours. H9C2 cardiomyocytes hypoxia/reoxygenation (H/R) was achieved by exposing the cells to glucose deprivation and hypoxia for 10 hours followed by reoxygenation 6 hours. We found that cardiac miR-503 expression level was down-regulated after induction of IRI compared with control, and it was also down-regulated in H9C2 cells after exposure to H/R. In vitro, cell viability was decreased after H/R treatment, and lactate dehydrogenase (LDH) activity was increased. Administration of an agomir designed to overexpress miR503-5p in cells before inducing H/R further reduced cell viability and elevated LDH activity. Moreover, proapoptotic Bax protein showed no significant change after overexpression of miR-503-5p in both normal and H/R states, while anti-apoptotic Bcl protein decreased significantly. We analyzed putative miR-503 targets using the TargetScan software, and found that the phosphoinositide-3-kinase regulatory subunit 1(PI3K p85) was one of the target genes. After overexpression of miR-503-5p, we found that PI3K p85 was decreased in both normal and H/R states. In addition, Akt1 and Akt2 as well as Phospho-Akt were decreased in H/R state, and were further decreased after miR-503-5p overexpressed. Furthermore, we also found that prosurvival protein phosphorylation of signal transducer and activator of transcription (STAT3) was decreased after exposure to H/R, and declined further after overexpression of miR-503-5p. It is concluded that miR-503-5p regulates H9C2 cardiomyocyte injury during H/R, and exacerbates cell injury by inhibiting the activation of prosurvival protein Akt and STAT3. |
Persistent Identifier | http://hdl.handle.net/10722/272825 |
ISSN | 2023 Impact Factor: 4.4 2023 SCImago Journal Rankings: 1.412 |
DC Field | Value | Language |
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dc.contributor.author | He, Y | - |
dc.contributor.author | Cai, Y | - |
dc.contributor.author | Liu, H | - |
dc.contributor.author | Irwin, MG | - |
dc.contributor.author | Xia, Z | - |
dc.date.accessioned | 2019-08-06T09:17:16Z | - |
dc.date.available | 2019-08-06T09:17:16Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Experimental Biology 2019 Meeting, Orlando, USA, 6-9 April 2019. In The FASEB Journal, 2019, v. 33 n. 1, Suppl., abstract no. 676.4 | - |
dc.identifier.issn | 0892-6638 | - |
dc.identifier.uri | http://hdl.handle.net/10722/272825 | - |
dc.description.abstract | Acute myocardial infarction (MI) is a leading cause of death worldwide, and the most effective therapy for reducing acute myocardial ischemic injury is myocardial reperfusion, while reperfusion itself can lead to further cardiomyocyte death, called ischemia/reperfusion injury (IRI). A number of microRNAs have been shown to be involved in IRI, however, the role of miR-503-5p, which is implicated in cancers, diabetes mellitus or pulmonary arterial hypertension, remains unknown in myocardial IRI. This study was aimed to investigate the effects of miR-503-5p in myocardial IRI. Cardiac miR-503-5p expression was measured in mice subjected to myocardial IRI achieved by occlusion of left anterior descending artery for 30 minutes followed by reperfusion for 2 hours. H9C2 cardiomyocytes hypoxia/reoxygenation (H/R) was achieved by exposing the cells to glucose deprivation and hypoxia for 10 hours followed by reoxygenation 6 hours. We found that cardiac miR-503 expression level was down-regulated after induction of IRI compared with control, and it was also down-regulated in H9C2 cells after exposure to H/R. In vitro, cell viability was decreased after H/R treatment, and lactate dehydrogenase (LDH) activity was increased. Administration of an agomir designed to overexpress miR503-5p in cells before inducing H/R further reduced cell viability and elevated LDH activity. Moreover, proapoptotic Bax protein showed no significant change after overexpression of miR-503-5p in both normal and H/R states, while anti-apoptotic Bcl protein decreased significantly. We analyzed putative miR-503 targets using the TargetScan software, and found that the phosphoinositide-3-kinase regulatory subunit 1(PI3K p85) was one of the target genes. After overexpression of miR-503-5p, we found that PI3K p85 was decreased in both normal and H/R states. In addition, Akt1 and Akt2 as well as Phospho-Akt were decreased in H/R state, and were further decreased after miR-503-5p overexpressed. Furthermore, we also found that prosurvival protein phosphorylation of signal transducer and activator of transcription (STAT3) was decreased after exposure to H/R, and declined further after overexpression of miR-503-5p. It is concluded that miR-503-5p regulates H9C2 cardiomyocyte injury during H/R, and exacerbates cell injury by inhibiting the activation of prosurvival protein Akt and STAT3. | - |
dc.language | eng | - |
dc.publisher | Federation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/ | - |
dc.relation.ispartof | The FASEB Journal | - |
dc.relation.ispartof | Experimental Biology 2019 Meeting | - |
dc.title | Overexpression of miR-503-5p exacerbates hypoxia/reoxygenation injury in H9C2 cardiomyocytes | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Cai, Y: caidavid@hku.hk | - |
dc.identifier.email | Irwin, MG: mgirwin@hku.hk | - |
dc.identifier.email | Xia, Z: zyxia@hkucc.hku.hk | - |
dc.identifier.authority | Irwin, MG=rp00390 | - |
dc.identifier.authority | Xia, Z=rp00532 | - |
dc.identifier.hkuros | 300363 | - |
dc.identifier.volume | 33 | - |
dc.identifier.issue | 1, Suppl. | - |
dc.identifier.spage | abstract no. 676.4 | - |
dc.identifier.epage | abstract no. 676.4 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 0892-6638 | - |