Imaging and Sensing of Cadmium in Cells

Abstract

Cadmium is one of the highly toxic transition metals for human beings and is known as a human carcinogen. Once humans are exposed to Cd(2+) on a chronic basis, Cd(2+) primarily accumulates in the liver and kidney where it forms complexes with small peptides and proteins via sulfhydryl groups. Complexed Cd(2+) or the ionic Cd(2+) is then taken up by target cells and tissues and exerts the toxicity. However, the question of how non-essential Cd(2+) crosses the cell membranes remains unanswered. Furthermore, the molecular mechanism of Cd(2+)-induced physiological signaling disruption in cells is still not fully elucidated. Investigations of Cd(2+) uptake kinetics, distributions, and concentrations in cells require chemical tools for its detection. Because of the easy use and high spatiotemporal resolution, optical imaging using fluorescence microscopy is a well-suited method for monitoring Cd(2+) in biological samples. This chapter summarizes design principles of small molecule fluorescent sensors for Cd(2+) detection in aqueous solution and their photophysical and metal-binding properties. Also the applications of probes for fluorescence imaging of Cd(2+) in a variety of cell types are demonstrated.

Celastrol Attenuates Cadmium‐Induced Neuronal Apoptosis via Inhibiting Ca2+‐CaMKII‐Dependent Akt/mTOR Pathway

“…However, it is worthy to explore whether changes in [Ca 2+ ] i levels, by taking advantage of multicolor imaging techniques with appropriate fluorescent indicators, could be simultaneously monitored with Cd 2+ levels. This may reveal the mechanistic details of Cd‐induced toxicity more substantially (Taki, ). More studies are needed, by designing the molecules that can distinguish the behaviors between Cd 2+ and Ca 2+ based on their distinct fluorescence features.…”

“…In this study, the fluorescent intensity of [Ca 2þ ] i is evaluated by imaging with a Ca 2þ indicator dye, Fluo-3/AM, based on multiple data of Fluo-3/AM as a suitable tool to record the effect of Cd on [Ca 2þ ] i in various living cells (Marchi et al, 2000;Wang et al, 2008Wang et al, , 2009Chen et al, 2011). Athough Fluo-3/AM could be responsive to intracellular free Cd 2þ in Cd-exposed neuronal cells, as shown by the data that Cd 2þ may enter neuronal cells through Ca 2þ channels (Taki, 2013), other studies have documented that Cd 2þ can produce the strongest probe signal rise in free solution and the lowest fluorescence increase in cells, underlining that interference of Cd 2þ with Fluo-3/AM does not affect Ca 2þ measurements in living cells (Marchi et al, 2000). Alterations of Fluo-3/AM produced by Cd 2þ in free solution become negligible in the cellular environment, and the responses of the probe within cells are consistent with expected Cd 2þ effects on cell Ca 2þ , rather than with the artifacts derived from metal/probe interactions (Marchi et al, 2000).…”

“…reveal the mechanistic details of Cd-induced toxicity more substantially (Taki, 2013). More studies are needed, by designing the molecules that can distinguish the behaviors between Cd 2þ and Ca 2þ based on their distinct fluorescence features.…”

Protective effect of low dose intra-articular cadmium on inflammation and joint destruction in arthritis

“…While Zn is necessary for a normal immune response 15, 16 , Cd inhibits the activity of anti-oxidative enzymes, mitochondrial electron transport-chain 17 and metalloproteins 18 with deleterious effects on cells. The possible contribution of Cd to RA is still unclear, ranging from its role as contributor to the induction of RA 19 , to its protective effect in a mouse model 20 .…”

Regulatory effects of zinc on cadmium-induced cytotoxicity in chronic inflammation

“…Zn is necessary for the normal immune response and for cell proliferation [9,10]. In contrast Cd inhibits the activity of anti-oxidative enzymes and the mitochondrial electron transport-chain [11], interferes with metalloproteins [12], inhibits the humoral and cellular immune response at low doses [13,14] and eventually enhances apoptosis or cell proliferation [15,16]. …”