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Phoenixin-14: detection and novel physiological implications in cardiac modulation and cardioprotection

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Abstract

Phoenixin-14 (PNX) is a newly identified peptide co-expressed in the hypothalamus with the anorexic and cardioactive Nesfatin-1. Like Nesfatin-1, PNX is able to cross the blood–brain barrier and this suggests a role in peripheral modulation. Preliminary mass spectrography data indicate that, in addition to the hypothalamus, PNX is present in the mammalian heart. This study aimed to quantify PNX expression in the rat heart, and to evaluate whether the peptide influences the myocardial function under basal condition and in the presence of ischemia/reperfusion (I/R). By ELISA the presence of PNX was detected in both hypothalamus and heart. In plasma of normal, but not of obese rats, the peptide concentrations increased after meal. Exposure of the isolated and Langendorff perfused rat heart to exogenous PNX induces a reduction of contractility and relaxation, without effects on coronary pressure and heart rate. As revealed by immunoblotting, these effects were accompanied by an increase of Erk1/2, Akt and eNOS phosphorylation. PNX (EC50 dose), administered after ischemia, induced post-conditioning-like cardioprotection. This was revealed by a smaller infarct size and a better systolic recovery with respect to those detected on hearts exposed to I/R alone. The peptide also activates the cardioprotective RISK and SAFE cascades and inhibits apoptosis. These effects were also observed in the heart of obese rats. Our data provide a first evidence on the peripheral activity of PNX and on its direct cardiomodulatory and cardioprotective role under both normal conditions and in the presence of metabolic disorders.

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Author notes

  1. C. Rocca, F. Scavello, Maria Carmela Cerra and Tommaso Angelone contributed equally to this work.

Authors and Affiliations

  1. Lab of Cellular and Molecular Cardiac Physiology, Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036, Arcavacata di Rende, CS, Italy

    C. Rocca, F. Scavello, M. C. Granieri, T. Pasqua & Tommaso Angelone

  2. National Institute of Cardiovascular Research (INRC), Bologna, Italy

    T. Pasqua, S. Imbrogno, A. Gattuso, R. Mazza, Maria Carmela Cerra & Tommaso Angelone

  3. Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy

    N. Amodio

  4. Lab of Cardiovascular Physiology, Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036, Arcavacata di Rende, CS, Italy

    S. Imbrogno, A. Gattuso, R. Mazza & Maria Carmela Cerra

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  1. C. Rocca
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Correspondence to Maria Carmela Cerra or Tommaso Angelone.

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The authors have nothing to disclose.

Funding

This research was supported by Doctorate in Life Sciences (RC, SF, GMC, IS, GA, RM, MCC, TA) and MIUR of Italy (ex 60%).

Electronic supplementary material

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18_2017_2661_MOESM1_ESM.tif

Supplementary Figure 1 Replicate effects of single concentration of PNX (0.5 nmol/L) on dLVP (n=3). Changes were evaluated as mean ± SE. Significant difference from control values (one-way ANOVA, Newman-Keuls test): *=p <0.05 (TIFF 945 kb)

18_2017_2661_MOESM2_ESM.tif

Supplementary Figure 2 a dLVP and b LVEDP at the end of reperfusion, and c IS in I/R–HFD, and PNX Post-HFD (n=3 for each group). Changes were evaluated as mean ± SE. There are no significant differences between groups (TIFF 1210 kb)

18_2017_2661_MOESM3_ESM.tif

Supplementary Figure 3 a dLVP and b LVEDP at the end of reperfusion, and c IS in I/R-SD group (for comparative purposes) and in inhibitor-treated groups (WT, L-NIO, PD and 5HD). There are no significant differences compared to I/R-SD group (TIFF 2246 kb)

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Rocca, C., Scavello, F., Granieri, M.C. et al. Phoenixin-14: detection and novel physiological implications in cardiac modulation and cardioprotection. Cell. Mol. Life Sci. 75, 743–756 (2018). https://doi.org/10.1007/s00018-017-2661-3

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