Cardioprotective kinase signaling to subsarcolemmal and interfibrillar mitochondria is mediated by caveolar structures

  • Wylly Ramsés García-NiñoEmail author
  • Francisco Correa
  • Julia Isabel Rodríguez-Barrena
  • Juan Carlos León-Contreras
  • Mabel Buelna-Chontal
  • Elizabeth Soria-Castro
  • Rogelio Hernández-Pando
  • José Pedraza-Chaverri
  • Cecilia ZazuetaEmail author
Original Contribution


The demonstration that caveolin-3 overexpression reduces myocardial ischemia/reperfusion injury and our own finding that multiprotein signaling complexes increase in mitochondria in association with caveolin-3 levels, led us to investigate the contribution of caveolae-driven extracellular signal-regulated kinases 1/2 (ERK1/2) on maintaining the function of cardiac mitochondrial subpopulations from reperfused hearts subjected to postconditioning (PostC). Rat hearts were isolated and subjected to ischemia/reperfusion and to PostC. Enhanced cardiac function, reduced infarct size and preserved ultrastructure of cardiomyocytes were associated with increased formation of caveolar structures, augmented levels of caveolin-3 and mitochondrial ERK1/2 activation in PostC hearts in both subsarcolemmal (SSM) and interfibrillar (IFM) subpopulations. Disruption of caveolae with methyl-β-cyclodextrin abolished cardioprotection in PostC hearts and diminished pho-ERK1/2 gold-labeling in both mitochondrial subpopulations in correlation with suppression of resistance to permeability transition pore opening. Also, differences between the mitochondrial subpopulations in the setting of PostC were evaluated. Caveolae disruption with methyl-β-cyclodextrin abolished the cardioprotective effect of postconditioning by inhibiting the interaction of ERK1/2 with mitochondria and promoted decline in mitochondrial function. SSM, which are particularly sensitive to reperfusion damage, take advantage of their location in cardiomyocyte boundary and benefit from the cardioprotective signaling driven by caveolae, avoiding injury propagation.


Cardioprotection Postconditioning Mitochondrial subpopulations Caveolae Mitochondrial ERK1/2 



The authors thank Rocio Torrico-Lavayen for technical assistance.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

All authors in this work gave their informed consent prior to their inclusion in the study. The manuscript does not contain clinical studies or patient data.


This work was supported by Grant 177527 to CZ, 181593 to FC and 220046 to JP-Ch from the National Council of Science and Technology (CONACYT), Mexico.

Supplementary material

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Supplementary material 1 (DOCX 20 kb)
395_2017_607_MOESM2_ESM.pptx (13.7 mb)
Supplementary material 2 (PPTX 14075 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Wylly Ramsés García-Niño
    • 1
    Email author
  • Francisco Correa
    • 1
  • Julia Isabel Rodríguez-Barrena
    • 1
  • Juan Carlos León-Contreras
    • 2
  • Mabel Buelna-Chontal
    • 1
  • Elizabeth Soria-Castro
    • 3
  • Rogelio Hernández-Pando
    • 2
  • José Pedraza-Chaverri
    • 4
  • Cecilia Zazueta
    • 1
    Email author
  1. 1.Departamento de Biomedicina CardiovascularInstituto Nacional de Cardiología “Ignacio Chávez”Ciudad de MéxicoMéxico
  2. 2.Departamento de PatologíaInstituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”Ciudad de MéxicoMéxico
  3. 3.Departamento de PatologíaInstituto Nacional de Cardiología “Ignacio Chávez”Ciudad de MéxicoMéxico
  4. 4.Departamento de Biología, Facultad de QuímicaUniversidad Nacional Autónoma de MéxicoCiudad de MéxicoMéxico

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