Cellular Zinc Fluxes and the Regulation of Apoptosis/Gene-Directed Cell Death

Abstract

The maintenance of discrete subcellular pools of zinc (Zn) is critical for the functional and structural integrity of cells. Among the important biological processes influenced by Zn is apoptosis, a process that is important in cellular homeostasis (an important cellular homeostatic process). It has also been identified as a major mechanism contributing to cell death in response to toxins and in disease, offering hope that novel therapies that target apoptotic pathways may be developed. Because Zn levels in the body can be increased in a relatively nontoxic manner, it may be possible to prevent or ameliorate degenerative disorders that are associated with high rates of apoptotic cell death. This review begins with brief introductions that address, first, the cellular biology of Zn, especially the critical labile Zn pools, and, second, the phenomenon of apoptosis. We then review the evidence relating Zn to apoptosis and address three major hypotheses: (1) that a specific pool or pools of intracellular labile Zn regulates apoptosis; (2) that systemic changes in Zn levels in the body, due to dietary factors, altered physiological states or disease, can influence cell susceptibility to apoptosis, and (3) that this altered susceptibility to apoptosis contributes to pathophysiological changes in the body. Other key issues are the identity of the molecular targets of Zn in the apoptotic cascade, the types of cells and tissues most susceptible to Zn-regulated apoptosis, the role of Zn as a coordinate regulator of mitosis and apoptosis and the apparent release of tightly bound intracellular pools of Zn during the later stages of apoptosis. This review concludes with a section highlighting areas of priority for future studies.

Epigallocatechin-3-gallate affects the growth of LNCaP cells via membrane fluidity and distribution of cellular zinc

“…This effect resulted from a direct action of zinc on the mitochondrial release of cytochrome c followed by caspase activation and cascading apoptotic events (Feng et al, 2000;. In contrast, most reports with other mammalian cells describe a role of zinc in the inhibition of apoptosis (Truong-Tran et al, 2000;Nodera et al, 2001). The most likely reason for this is that the levels of zinc to which the cells were exposed were lower and exposed time of cells was shorter than that of the present work.…”

Zinc-mediated regulation of caspases activity: dose-dependent inhibition or activation of caspase-3 in the human Burkitt lymphoma B cells (Ramos)

“…This may indicate that target molecules are primarily cytoplasmic as caspases. 19 Zn 2+ directly inhibits the activity in vitro of various recombinant caspases including caspase-3, -6, -7 and -8. 20,21 These caspases are cysteine-related proteases, which are synthesized as inactive proenzymes and activated in vivo during most apoptotic processes.…”

EFEITO ANTICARCINOGÊNICO DO GERIOOX® EM Drosophila melanogaster

“…É uma resposta de morte celular frente a agentes tóxicos e a desregulação é crucial no mecanismo de várias patologias, inclusive o câncer. Existem evidências de que o zinco e vitamina E, também presentes no Gerioox®, impedem que as células tumorais continuem o ciclo celular, interrompendo-o na fase G1 e conduzindo as mesmas a apoptose (LAMSONL; BRIGNALL, 1999;TRUONG-TRAN et al, 2000).…”