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Article: Globular adiponectin, acting via AdipoR1/APPL1, protects H9c2 cells from hypoxia/reoxygenation-induced apoptosis

TitleGlobular adiponectin, acting via AdipoR1/APPL1, protects H9c2 cells from hypoxia/reoxygenation-induced apoptosis
Authors
Issue Date2011
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
Citation
Plos One, 2011, v. 6 n. 4 How to Cite?
AbstractCardiomyocyte apoptosis is an important remodeling event contributing to heart failure and adiponectin may mediate cardioprotective effects at least in part via attenuating apoptosis. Here we used hypoxia-reoxygenation (H/R) induced apoptosis in H9c2 cells to examine the effect of adiponectin and cellular mechanisms of action. We first used TUNEL labeling in combination with laser scanning cytometry to demonstrate that adiponectin prevented H/R-induced DNA fragmentation. The anti-apoptotic effect of adiponectin was also verified via attenuation of H/R-induced phosphatidylserine exposure using annexin V binding. H/R-induced apoptosis via the mitochondrial-mediated intrinsic pathway of apoptosis as assessed by cytochrome c release into cytosol and caspase-3 activation, both of which were attenuated by adiponectin. Mechanistically, we demonstrated that adiponectin enhanced anti-oxidative potential in these cells which led to attenuation of the increase in intracellular reactive oxygen species (ROS) caused by H/R. To further address the mechanism of adiponctins anti-apoptotic effects we used siRNA to efficiently knockdown adiponectin receptor (AdipoR1) expression and found that this attenuated the protective effects of adiponectin on ROS production and caspase 3 activity. Knockdown of APPL1, an important intracellular binding partner for AdipoR, also significantly reduced the ability of adiponectin to prevent H/R-induced ROS generation and caspase 3 activity. In summary, H/R-induced ROS generation and activation of the intrinsic apoptotic pathway was prevented by adiponectin via AdipoR1/APPL1 signaling and increased anti-oxidant potential. © 2011 Park et al.
Persistent Identifierhttp://hdl.handle.net/10722/139454
ISSN
2015 Impact Factor: 3.057
2015 SCImago Journal Rankings: 1.395
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Heart and Stroke Foundation of Canada
Canadian Institutes of Health Research (CIHR)RT734076
Natural Sciences and Engineering Research Council of Canada (NSERC)
Alberta Heritage Foundation for Medical Research
Funding Information:

This work was supported by Heart and Stroke Foundation of Canada via a Grant-in-Aid to GS. GS and DW also acknowledge support from The Canadian Institutes of Health Research (CIHR) China Collaborative grant, MP holds a Natural Sciences and Engineering Research Council of Canada (NSERC) postgraduate studentship award. Work by XLZ was partially supported by Canadian Institutes of Health Research (RT734076) and XLZ is the recipient of Senior Scholar Award of Alberta Heritage Foundation for Medical Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorPark, Men_HK
dc.contributor.authorYoun, Ben_HK
dc.contributor.authorZheng, XLen_HK
dc.contributor.authorWu, Den_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorSweeney, Gen_HK
dc.date.accessioned2011-09-23T05:50:14Z-
dc.date.available2011-09-23T05:50:14Z-
dc.date.issued2011en_HK
dc.identifier.citationPlos One, 2011, v. 6 n. 4en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/139454-
dc.description.abstractCardiomyocyte apoptosis is an important remodeling event contributing to heart failure and adiponectin may mediate cardioprotective effects at least in part via attenuating apoptosis. Here we used hypoxia-reoxygenation (H/R) induced apoptosis in H9c2 cells to examine the effect of adiponectin and cellular mechanisms of action. We first used TUNEL labeling in combination with laser scanning cytometry to demonstrate that adiponectin prevented H/R-induced DNA fragmentation. The anti-apoptotic effect of adiponectin was also verified via attenuation of H/R-induced phosphatidylserine exposure using annexin V binding. H/R-induced apoptosis via the mitochondrial-mediated intrinsic pathway of apoptosis as assessed by cytochrome c release into cytosol and caspase-3 activation, both of which were attenuated by adiponectin. Mechanistically, we demonstrated that adiponectin enhanced anti-oxidative potential in these cells which led to attenuation of the increase in intracellular reactive oxygen species (ROS) caused by H/R. To further address the mechanism of adiponctins anti-apoptotic effects we used siRNA to efficiently knockdown adiponectin receptor (AdipoR1) expression and found that this attenuated the protective effects of adiponectin on ROS production and caspase 3 activity. Knockdown of APPL1, an important intracellular binding partner for AdipoR, also significantly reduced the ability of adiponectin to prevent H/R-induced ROS generation and caspase 3 activity. In summary, H/R-induced ROS generation and activation of the intrinsic apoptotic pathway was prevented by adiponectin via AdipoR1/APPL1 signaling and increased anti-oxidant potential. © 2011 Park et al.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAdiponectin - pharmacology-
dc.subject.meshApoptosis - drug effects-
dc.subject.meshCarrier Proteins - genetics - metabolism-
dc.subject.meshNerve Tissue Proteins - deficiency - genetics - metabolism-
dc.subject.meshOxygen - metabolism-
dc.titleGlobular adiponectin, acting via AdipoR1/APPL1, protects H9c2 cells from hypoxia/reoxygenation-induced apoptosisen_HK
dc.typeArticleen_HK
dc.identifier.emailXu, A:amxu@hkucc.hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0019143en_HK
dc.identifier.pmid21552570-
dc.identifier.pmcidPMC3084258-
dc.identifier.scopuseid_2-s2.0-79955738387en_HK
dc.identifier.hkuros194040en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955738387&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue4en_HK
dc.identifier.spagee19143en_US
dc.identifier.epagee19143en_US
dc.identifier.isiWOS:000290020700032-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridPark, M=16426070700en_HK
dc.identifier.scopusauthoridYoun, B=7005009217en_HK
dc.identifier.scopusauthoridZheng, XL=18234418900en_HK
dc.identifier.scopusauthoridWu, D=7404297751en_HK
dc.identifier.scopusauthoridXu, A=7202655409en_HK
dc.identifier.scopusauthoridSweeney, G=7102852659en_HK

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