Free zinc ions outside a narrow concentration range are toxic to a variety of cells in vitro

Abstract

The zinc(II) ion has recently been implicated in a number of novel functions and pathologies in loci as diverse as the brain, retina, small intestine, prostate, heart, pancreas and immune system. Zinc ions are a required nutrient but elevated concentrations are known to kill cells in vitro. Paradoxical observations regarding zinc's effects have appeared frequently in the literature, and often their physiological relevance is unclear. We found that for PC-12, HeLa and HT-29 cell lines as well as primary cultures of cardiac myocytes and neurons in vitro in differing media, approximately 5 nmol/ L free zinc (pZn = 8.3, where pZn is defined as − log 10 [free Zn 2+ ]) produced apparently healthy cells, but 20-fold higher or (in one case) lower concentrations were usually harmful as judged by multiple criteria. These results indicate that (1) the free zinc ion levels of media should be controlled with a metal ion buffer; (2) adding zinc or strong zinc ligands to an insufficiently buffered medium may lead to unpredictably low or high free zinc levels that are often harmful to cells; and (3) it is generally desirable to measure free zinc ion levels due to the presence of contaminating zinc in many biochemicals and unknown buffering capacity of many media.

Age-related histological and zinc content changes in adult nonhyperplastic prostate glands

“…The stated level of Zn mass fraction in the prostate tissue is higher than mean values of this element's content in all other soft and hard tissues of human body, including skeletal muscle, liver, lung, kidney, and bones (ICRP 1975;Iyengar et al 1978;Iyengar 1998). Excessive Zn concentrations may be harmful to normal metabolism of cells (Bozym et al 2010) and partially responsible for an age-related enlargement of the prostate. For example, Zn enhances the activity of telomerase (Nemoto et al 2000), an enzyme thought to be responsible for unlimited cell proliferation (Sommerfeld et al 1996).…”

Metallothionein 1G and Zinc Sensitize Human Colorectal Cancer Cells to Chemotherapy

“…Zinc is a required nutrient for proliferation, but elevated concentrations are known to promote cell death by many different mechanisms (15). Free zinc ions exist in the picomolar range and may be considered negligible due to tight regulation by zinc transporters, MTs, and organelle sequestration (16).…”

Extracellular pH Regulates Zinc Signaling via an Asp Residue of the Zinc-sensing Receptor (ZnR/GPR39)

“…Therefore, a possible explanation is that the constitutive release of IP 3 may not be sufficiently strong to trigger Ca 2ϩ release. Alternatively, the constitutive activity may also be attributed to varying residual Zn 2ϩ often found in physiological solutions (10,(55)(56)(57). Finally, the apparent constitutive activity of the H17A/H19A or D313A mutants in the previous study (24) may have masked their Zn 2ϩ -dependent activity.…”