Impact of Labile Zinc on Heart Function: From Physiology to Pathophysiology

Abstract

Zinc plays an important role in biological systems as bound and histochemically reactive labile Zn2+. Although Zn2+ concentration is in the nM range in cardiomyocytes at rest and increases dramatically under stimulation, very little is known about precise mechanisms controlling the intracellular distribution of Zn2+ and its variations during cardiac function. Recent studies are focused on molecular and cellular aspects of labile Zn2+ and its homeostasis in mammalian cells and growing evidence clarified the molecular mechanisms underlying Zn2+-diverse functions in the heart, leading to the discovery of novel physiological functions of labile Zn2+ in parallel to the discovery of subcellular localization of Zn2+-transporters in cardiomyocytes. Additionally, important experimental data suggest a central role of intracellular labile Zn2+ in excitation-contraction coupling in cardiomyocytes by shaping Ca2+ dynamics. Cellular labile Zn2+ is tightly regulated against its adverse effects through either Zn2+-transporters, Zn2+-binding molecules or Zn2+-sensors, and, therefore plays a critical role in cellular signaling pathways. The present review summarizes the current understanding of the physiological role of cellular labile Zn2+ distribution in cardiomyocytes and how a remodeling of cellular Zn2+-homeostasis can be important in proper cell function with Zn2+-transporters under hyperglycemia. We also emphasize the recent investigations on Zn2+-transporter functions from the standpoint of human heart health to diseases together with their clinical interest as target proteins in the heart under pathological condition, such as diabetes.

Mitochondria-Targeting Antioxidant Provides Cardioprotection through Regulation of Cytosolic and Mitochondrial Zn2+ Levels with Re-Distribution of Zn2+-Transporters in Aged Rat Cardiomyocytes

“…The [Zn 2+ ] i -homeostasis and the suborganelle levels of [Zn 2+ ] are altered under pathological conditions, including hyperglycemia in cardiomyocytes [37,38]. Moreover, we have shown that a re-distribution of the expression level of some Zn 2+ -transporters can play an important contribution to those changes [37,39].…”

Concentrations of Mg, Ca, Fe, Cu, Zn, P and anthropometric and biochemical parameters in adults with chronic heart failure

“…Some studies have found decreased Zn concentrations in HF patients, but there have also been reports where no significant differences were observed in terms of serum Zn levels between HF patients and the control group ( Kosar et al, 2006 ; Ghaemian et al, 2011 ; Alexanian et al, 2014 ; Salehifar et al, 2008 ; Shokrzadeh et al, 2009 ). Zn plays a major role in controlling cardiac contractility in cardiomyocytes, which may ultimately improve cardiac function ( Turan & Tuncay, 2017 ), hence maintaining normal Zn levels seems to serve a protective role in HF patients.…”

Peer Review #1 of "Concentrations of Mg, Ca, Fe, Cu, Zn, P and anthropometric and biochemical parameters in adults with chronic heart failure (v0.1)"

“…Manuscript to be reviewed Ghaemian et al, 2011;Alexanian et al, 2014;Salehifar et al, 2008;Shokrzadeh et al, 2009). Zn plays a major role in controlling cardiac contractility in cardiomyocytes, which may ultimately improve cardiac function (Turan et al, 2017), hence maintaining normal Zn levels seems to serve a protective role in HF patients.…”