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Pregled bibliografske jedinice broj: 856738

Cdk1, PKCδ and calcineurin-mediated Drp1 pathway contributes to mitochondrial fission- induced cardiomyocyte death

Žaja, Ivan; Bai, X.; Liu, Y.; Kikuchi, C.; Došenović, Svjetlana; Yan, Y.; Canfield, S.G.; Bošnjak, Željko J.
Cdk1, PKCδ and calcineurin-mediated Drp1 pathway contributes to mitochondrial fission- induced cardiomyocyte death // Biochemical and biophysical research communications, 453 (2014), 4; 710-721 doi:10.1016/j.bbrc.2014.09.144 (međunarodna recenzija, članak, znanstveni)

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Naslov
Cdk1, PKCδ and calcineurin-mediated Drp1 pathway contributes to mitochondrial fission- induced cardiomyocyte death

Autori
Žaja, Ivan ; Bai, X. ; Liu, Y. ; Kikuchi, C. ; Došenović, Svjetlana ; Yan, Y. ; Canfield, S.G. ; Bošnjak, Željko J.

Izvornik
Biochemical and biophysical research communications (0006-291X) 453 (2014), 4; 710-721

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
cardiomyocyte death, calcineurin

Sažetak
Myocardial ischemia-reperfusion (I/R) injury is one of the leading causes of death and disability worldwide. Mitochondrial fission has been shown to be involved in cardiomyocyte death. However, molecular machinery involved in mitochondrial fission during I/R injury has not yet been completely understood. In this study we aimed to investigate molecular mechanisms of controlling activation of dynamin-related protein 1 (Drp1, a key protein in mitochondrial fission) during anoxia-reoxygenation (A/R) injury of HL1 cardiomyocytes. A/R injury induced cardiomyocyte death accompanied by the increases of mitochondrial fission, reactive oxygen species (ROS) production and activated Drp1 (pSer616 Drp1), and decrease of inactivated Drp1 (pSer637 Drp1) while mitochondrial fusion protein levels were not significantly changed. Blocking Drp1 activity with mitochondrial division inhibitor mdivi1 attenuated cell death, mitochondrial fission, and Drp1 activation after A/R. Trolox, a ROS scavenger, decreased pSer616 Drp1 level and mitochondrial fission after A/R. Immunoprecipitation assay further indicates that cyclin dependent kinase 1 (Cdk1) and protein kinase C isoform delta (PKCδ) bind Drp1, thus increasing mitochondrial fission. Inhibiting Cdk1 and PKCδ attenuated the increases in pSer616 Drp1, mitochondrial fission, and cardiomyocyte death. FK506, a calcineurin inhibitor, blocked the decrease in expression of inactivated pSer637 Drp1 and mitochondrial fission. Our findings reveal the following novel molecular mechanisms controlling mitochondrial fission during A/R injury of cardiomyocytes: (1) ROS are upstream initiators of mitochondrial fission ; and (2) the increased mitochondrial fission is resulted from both increased activation and decreased inactivation of Drp1 through Cdk1, PKCδ, and calcineurin-mediated pathways, respectively.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA

Ustanove:
Medicinski fakultet, Split

Profili:

Avatar Url Svjetlana Došenović (autor)

Avatar Url Ivan Žaja (autor)

Poveznice na cjeloviti tekst rada:

doi www.sciencedirect.com dx.doi.org

Citiraj ovu publikaciju:

Žaja, Ivan; Bai, X.; Liu, Y.; Kikuchi, C.; Došenović, Svjetlana; Yan, Y.; Canfield, S.G.; Bošnjak, Željko J.
Cdk1, PKCδ and calcineurin-mediated Drp1 pathway contributes to mitochondrial fission- induced cardiomyocyte death // Biochemical and biophysical research communications, 453 (2014), 4; 710-721 doi:10.1016/j.bbrc.2014.09.144 (međunarodna recenzija, članak, znanstveni)
Žaja, I., Bai, X., Liu, Y., Kikuchi, C., Došenović, S., Yan, Y., Canfield, S. & Bošnjak, Ž. (2014) Cdk1, PKCδ and calcineurin-mediated Drp1 pathway contributes to mitochondrial fission- induced cardiomyocyte death. Biochemical and biophysical research communications, 453 (4), 710-721 doi:10.1016/j.bbrc.2014.09.144.
@article{article, author = {\v{Z}aja, Ivan and Bai, X. and Liu, Y. and Kikuchi, C. and Do\v{s}enovi\'{c}, Svjetlana and Yan, Y. and Canfield, S.G. and Bo\v{s}njak, \v{Z}eljko J.}, year = {2014}, pages = {710-721}, DOI = {10.1016/j.bbrc.2014.09.144}, keywords = {cardiomyocyte death, calcineurin}, journal = {Biochemical and biophysical research communications}, doi = {10.1016/j.bbrc.2014.09.144}, volume = {453}, number = {4}, issn = {0006-291X}, title = {Cdk1, PKCδ and calcineurin-mediated Drp1 pathway contributes to mitochondrial fission- induced cardiomyocyte death}, keyword = {cardiomyocyte death, calcineurin} }
@article{article, author = {\v{Z}aja, Ivan and Bai, X. and Liu, Y. and Kikuchi, C. and Do\v{s}enovi\'{c}, Svjetlana and Yan, Y. and Canfield, S.G. and Bo\v{s}njak, \v{Z}eljko J.}, year = {2014}, pages = {710-721}, DOI = {10.1016/j.bbrc.2014.09.144}, keywords = {cardiomyocyte death, calcineurin}, journal = {Biochemical and biophysical research communications}, doi = {10.1016/j.bbrc.2014.09.144}, volume = {453}, number = {4}, issn = {0006-291X}, title = {Cdk1, PKCδ and calcineurin-mediated Drp1 pathway contributes to mitochondrial fission- induced cardiomyocyte death}, keyword = {cardiomyocyte death, calcineurin} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE

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