Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/178515
Title: Neurohormonal activation induces intracellular iron deficiency and mitochondrial dysfunction in cardiac cells
Author: Tajes, Marta
Díez López, Carles
Enjuanes, Cristina
Moliner, Pedro
Ferreiro, José Luis
Garay, Alberto
Jiménez Marrero, Santiago
Yun, Sergi
Sosa, S. G.
Alcoberro, L.
González Costello, J.
García Romero, Elena
Yañez Bisbe, L.
Benito, B.
Comín Colet, Josep
Keywords: Aturada cardíaca
Dèficit de ferro
Cardiac arrest
Iron deficiency diseases
Issue Date: 17-May-2021
Publisher: Springer Nature
Abstract: Background: Iron deficiency (ID) is common in patients with heart failure (HF) and is associated with poor outcomes, yet its role in the pathophysiology of HF is not well-defined. We sought to determine the consequences of HF neurohormonal activation in iron homeostasis and mitochondrial function in cardiac cells. Methods: HF was induced in C57BL/6 mice by using isoproterenol osmotic pumps and embryonic rat heart-derived H9c2 cells were subsequently challenged with Angiotensin II and/or Norepinephrine. The expression of several genes and proteins related to intracellular iron metabolism were assessed by Real time-PCR and immunoblotting, respectively. The intracellular iron levels were also determined. Mitochondrial function was analyzed by studying the mitochondrial membrane potential, the accumulation of radical oxygen species (ROS) and the adenosine triphosphate (ATP) production. Results: Hearts from isoproterenol-stimulated mice showed a decreased in both mRNA and protein levels of iron regulatory proteins, transferrin receptor 1, ferroportin 1 and hepcidin compared to control mice. Furthermore, mitoferrin 2 and mitochondrial ferritin were also downregulated in the hearts from HF mice. Similar data regarding these key iron regulatory molecules were found in the H9c2 cells challenged with neurohormonal stimuli. Accordingly, a depletion of intracellular iron levels was found in the stimulated cells compared to non-stimulated cells, as well as in the hearts from the isoproterenol-induced HF mice. Finally, neurohormonal activation impaired mitochondrial function as indicated by the accumulation of ROS, the impaired mitochondrial membrane potential and the decrease in the ATP levels in the cardiac cells. Conclusions: HF characteristic neurohormonal activation induced changes in the regulation of key molecules involved in iron homeostasis, reduced intracellular iron levels and impaired mitochondrial function. The current results suggest that iron could be involved in the pathophysiology of HF.
Note: Reproducció del document publicat a: https://doi.org/10.1186/s13578-021-00605-5
It is part of: Cell & Bioscience, 2021, vol. 11
URI: http://hdl.handle.net/2445/178515
Related resource: https://doi.org/10.1186/s13578-021-00605-5
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Clíniques)

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