The Critical Roles of Zinc: Beyond Impact on Myocardial Signaling.
Zinc has been considered as a vital constituent of proteins, including enzymes. Mobile reactive zinc (Zn(2+)) is the key form of zinc involved in signal transductions, which are mainly driven by its binding to proteins or the release of zinc from proteins, possibly via a redox switch. There has been growing evidence of zinc's critical role in cell signaling, due to its flexible coordination geometry and rapid shifts in protein conformation to perform biological reactions. The importance and complexity of Zn(2+) activity has been presumed to parallel the degree of calcium's participation in cellular processes. Whole body and cellular Zn(2+) levels are largely regulated by metallothioneins (MTs), Zn(2+) importers (ZIPs), and Zn(2+) transporters (ZnTs). Numerous proteins involved in signaling pathways, mitochondrial metabolism, and ion channels that play a pivotal role in controlling cardiac contractility are common targets of Zn(2+). However, these regulatory actions of Zn(2+) are not limited to the function of the heart, but also extend to numerous other organ systems, such as the central nervous system, immune system, cardiovascular tissue, and secretory glands, such as the pancreas, prostate, and mammary glands. In this review, the regulation of cellular Zn(2+) levels, Zn(2+)-mediated signal transduction, impacts of Zn(2+) on ion channels and mitochondrial metabolism, and finally, the implications of Zn(2+) in health and disease development were outlined to help widen the current understanding of the versatile and complex roles of Zn(2+).
Department of Integrated Biomedical Science, Cardiovascular and Metabolic disease Center, College of Medicine, Inje University, Busan 614-735, Korea.
Sung Ryul
SR
Lee
Department of Physiology, Graduate School of Inje University, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Korea.
Su Jin
SJ
Noh
Department of Physiology, Graduate School of Inje University, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Korea.
Julius Ryan
JR
Pronto
Department of Physiology, Graduate School of Inje University, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Korea.
Yu Jeong
YJ
Jeong
Department of Integrated Biomedical Science, Cardiovascular and Metabolic disease Center, College of Medicine, Inje University, Busan 614-735, Korea.
Hyoung Kyu
HK
Kim
College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Korea.
In Sung
IS
Song
Department of Physiology and Pathophysiology, Tianjin Medical University, Tainjin 300070, P.R. China.
Zhelong
Z
Xu
Soonchunhyang Institute of Medio-bio Science (SIMS), Soonchunhyang University, Cheonan 336-745, Korea.
Hyog Young
HY
Kwon
Department of Life Science, Gachon University, Seongnam 461-701, Korea.
Se Chan
SC
Kang
Department of Herbal Medicine Resource, Kangwon National University, Samcheok 245-711, Korea.
Eun-Hwa
EH
Sohn
College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Korea.
Kyung Soo
KS
Ko
College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Korea.
Byoung Doo
BD
Rhee
College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Korea.
Nari
N
Kim
College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan 614-735, Korea.
Jin
J
Han
Metallothionein; Signal Transduction; Zinc; Zinc exporter; Zinc importer