File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
  • Find via Find It@HKUL
Supplementary

Conference Paper: MicroRNA-181c-5p exacerbates apoptotic cell death in H9C2 cardiomyocytes during hypoxia/reoxygenation

TitleMicroRNA-181c-5p exacerbates apoptotic cell death in H9C2 cardiomyocytes during hypoxia/reoxygenation
Authors
Issue Date2018
PublisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/
Citation
Experimental Biology 2018 Meeting, San Diego, CA, 21-25 April 2018 in The FASEB Journal, 2018, v. 32 n. 1, suppl., p. abstract no. 698.10 How to Cite?
AbstractMyocardial ischemia is a leading cause of death all over the world. The most effective way to salvage ischemic myocardium is the restoration of blood flow, but reperfusion itself may cause additional tissue injury called “ischemia/reperfusion injury (I/RI)”. Activation of cell apoptosis is a major form of cell death during myocardial I/RI. Thus, examining ways to control cell apoptosis has important clinical significance for improving post-ischemic recovery. MicroRNAs (miR), small non-coding RNA molecules that regulate gene expression by inhibiting mRNA translation and/or inducing mRNA degradation, play a crucial role in various cellular and biological processes. The clinical evidence demonstrated that miR-181c was significantly up-regulated in the early phase of myocardial infarction. However, whether or not miR-181c mediates cardiac I/RI through cell apoptosis pathway is unknown. Thus, the present study aimed to investigate the role of miR-181c in hypoxia/reoxygenation (H/R, 6 hours hypoxia followed by6 hours reoxygenation) induced cell injury in H9C2 cardiomyocytes and its possible mechanism. The results showed that H/R significantly increased the expression of miR-181c-5p (P<0.05 vs. Control) but not miR-181c-3p in H9C2 cells. In line with this, in an in vivo rat cardiac I/RI model (30 min left anterior descending coronary artery ligation followed by 2 hours reperfusion), miR-181c-5p expression was also significantly increased (P<0.05 vs. Control), suggesting that miR-181c-5p may be involved in the pathogenesis of cardiac I/RI. Under the experimental setting, H/R significantly induced H9C2 cells injury, as evidenced by increased lactic acid dehydrogenase (LDH) leakage (cell injury marker, P<0.05 vs. Control) and reduced cell viability (MTT assay, P<0.05 vs. Control). Furthermore, H/R-induced cell injury was accompanied by increased cleaved caspase-3 expression and more TUNEL positive cells (markers of cell apoptosis, P<0.05 vs. Control), but no significant changes in the expression of Bcl-2 (anti-apoptotic) and Bax (pro-apoptotic), suggesting that H/R induces caspase-3 dependent cell apoptosis, which was independent of the intrinsic mitochondrial pathway. To demonstrate the potential role of miR-181c-5p in H/R-induced cell injury, H9C2 cells were transfected with the miR-181c-5pagomir or its negative control. The overexpression of miR-181c-5psignificantly aggravated H/R-induced cell injury (increased LDH level and reduced cell viability, P<0.05 vs.H/R) and exacerbated H/R-induced cell apoptosis (greater cleaved caspases-3 expression and more TUNEL positive cells, P<0.05 vs.H/R). In contrast, in H9C2 cells transfected with miR-181c-5p antagomir, inhibition of miR-181c-5p significantly suppressed H/R-induced enhancement of LDH level and cleaved caspase-3 expression and apoptotic cell death(P<0.05 vs.H/R). It is concluded that in H9C2 cells, H/R may induce cardiomyocytes apoptosis via enhanced miR-181c-5p expression, which may yield novel strategies to combat myocardial I/RI.
DescriptionAbstract
Persistent Identifierhttp://hdl.handle.net/10722/264569
ISSN
2019 Impact Factor: 4.966
2015 SCImago Journal Rankings: 2.775

 

DC FieldValueLanguage
dc.contributor.authorGe, L-
dc.contributor.authorMa, H-
dc.contributor.authorCai, Y-
dc.contributor.authorPang, L-
dc.contributor.authorIrwin, MG-
dc.contributor.authorXia, Z-
dc.date.accessioned2018-10-22T07:57:08Z-
dc.date.available2018-10-22T07:57:08Z-
dc.date.issued2018-
dc.identifier.citationExperimental Biology 2018 Meeting, San Diego, CA, 21-25 April 2018 in The FASEB Journal, 2018, v. 32 n. 1, suppl., p. abstract no. 698.10-
dc.identifier.issn0892-6638-
dc.identifier.urihttp://hdl.handle.net/10722/264569-
dc.descriptionAbstract-
dc.description.abstractMyocardial ischemia is a leading cause of death all over the world. The most effective way to salvage ischemic myocardium is the restoration of blood flow, but reperfusion itself may cause additional tissue injury called “ischemia/reperfusion injury (I/RI)”. Activation of cell apoptosis is a major form of cell death during myocardial I/RI. Thus, examining ways to control cell apoptosis has important clinical significance for improving post-ischemic recovery. MicroRNAs (miR), small non-coding RNA molecules that regulate gene expression by inhibiting mRNA translation and/or inducing mRNA degradation, play a crucial role in various cellular and biological processes. The clinical evidence demonstrated that miR-181c was significantly up-regulated in the early phase of myocardial infarction. However, whether or not miR-181c mediates cardiac I/RI through cell apoptosis pathway is unknown. Thus, the present study aimed to investigate the role of miR-181c in hypoxia/reoxygenation (H/R, 6 hours hypoxia followed by6 hours reoxygenation) induced cell injury in H9C2 cardiomyocytes and its possible mechanism. The results showed that H/R significantly increased the expression of miR-181c-5p (P<0.05 vs. Control) but not miR-181c-3p in H9C2 cells. In line with this, in an in vivo rat cardiac I/RI model (30 min left anterior descending coronary artery ligation followed by 2 hours reperfusion), miR-181c-5p expression was also significantly increased (P<0.05 vs. Control), suggesting that miR-181c-5p may be involved in the pathogenesis of cardiac I/RI. Under the experimental setting, H/R significantly induced H9C2 cells injury, as evidenced by increased lactic acid dehydrogenase (LDH) leakage (cell injury marker, P<0.05 vs. Control) and reduced cell viability (MTT assay, P<0.05 vs. Control). Furthermore, H/R-induced cell injury was accompanied by increased cleaved caspase-3 expression and more TUNEL positive cells (markers of cell apoptosis, P<0.05 vs. Control), but no significant changes in the expression of Bcl-2 (anti-apoptotic) and Bax (pro-apoptotic), suggesting that H/R induces caspase-3 dependent cell apoptosis, which was independent of the intrinsic mitochondrial pathway. To demonstrate the potential role of miR-181c-5p in H/R-induced cell injury, H9C2 cells were transfected with the miR-181c-5pagomir or its negative control. The overexpression of miR-181c-5psignificantly aggravated H/R-induced cell injury (increased LDH level and reduced cell viability, P<0.05 vs.H/R) and exacerbated H/R-induced cell apoptosis (greater cleaved caspases-3 expression and more TUNEL positive cells, P<0.05 vs.H/R). In contrast, in H9C2 cells transfected with miR-181c-5p antagomir, inhibition of miR-181c-5p significantly suppressed H/R-induced enhancement of LDH level and cleaved caspase-3 expression and apoptotic cell death(P<0.05 vs.H/R). It is concluded that in H9C2 cells, H/R may induce cardiomyocytes apoptosis via enhanced miR-181c-5p expression, which may yield novel strategies to combat myocardial I/RI.-
dc.languageeng-
dc.publisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/-
dc.relation.ispartofThe FASEB Journal-
dc.titleMicroRNA-181c-5p exacerbates apoptotic cell death in H9C2 cardiomyocytes during hypoxia/reoxygenation-
dc.typeConference_Paper-
dc.identifier.emailCai, Y: caidavid@hku.hk-
dc.identifier.emailIrwin, MG: mgirwin@hku.hk-
dc.identifier.emailXia, Z: zyxia@hkucc.hku.hk-
dc.identifier.authorityIrwin, MG=rp00390-
dc.identifier.authorityXia, Z=rp00532-
dc.identifier.hkuros295392-
dc.identifier.volume32-
dc.identifier.issue1, suppl.-
dc.identifier.spageabstract no. 698.10-
dc.identifier.epageabstract no. 698.10-
dc.publisher.placeUnited States-
dc.identifier.issnl0892-6638-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats