A Brief Overview from the Physiological and Detrimental Roles of Zinc Homeostasis via Zinc Transporters in the Heart.


Department of Biophysics, Faculty of Medicine, Ankara University, Ankara, Turkey. [Email]


Zinc (mostly as free/labile Zn2+) is an essential structural constituent of many proteins, including enzymes in cellular signaling pathways via functioning as an important signaling molecule in mammalian cells. In cardiomyocytes at resting condition, intracellular labile Zn2+ concentration ([Zn2+]i) is in the nanomolar range, whereas it can increase dramatically under pathological conditions, including hyperglycemia, but the mechanisms that affect its subcellular redistribution is not clear. Therefore, overall, very little is known about the precise mechanisms controlling the intracellular distribution of labile Zn2+, particularly via Zn2+ transporters during cardiac function under both physiological and pathophysiological conditions. Literature data demonstrated that [Zn2+]i homeostasis in mammalian cells is primarily coordinated by Zn2+ transporters classified as ZnTs (SLC30A) and ZIPs (SLC39A). To identify the molecular mechanisms of diverse functions of labile Zn2+ in the heart, the recent studies focused on the discovery of subcellular localization of these Zn2+ transporters in parallel to the discovery of novel physiological functions of [Zn2+]i in cardiomyocytes. The present review summarizes the current understanding of the role of [Zn2+]i changes in cardiomyocytes under pathological conditions, and under high [Zn2+]i and how Zn2+ transporters are important for its subcellular redistribution. The emerging importance and the promise of some Zn2+ transporters for targeted cardiac therapy against pathological stimuli are also provided. Taken together, the review clearly outlines cellular control of cytosolic Zn2+ signaling by Zn2+ transporters, the role of Zn2+ transporters in heart function under hyperglycemia, the role of Zn2+ under increased oxidative stress and ER stress, and their roles in cancer are discussed.


Endoplasmic reticulum stress,Heart failure,Intracellular free zinc,Left ventricle,Zinc transporters,