HaloTag-Based Hybrid Targetable and Ratiometric Sensors for Intracellular Zinc

2020 ◽  
Vol 15 (2) ◽  
pp. 396-406 ◽  
Author(s):  
Melissa L. Zastrow ◽  
Zhen Huang ◽  
Stephen J. Lippard
Keyword(s):  
Intracellular Zinc ◽  
Ratiometric Sensors

scholarly journals Alterations in ZnT1 expression and function lead to impaired intracellular zinc homeostasis in cancer

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Adrian Israel Lehvy ◽  
Guy Horev ◽  
Yarden Golan ◽  
Fabian Glaser ◽  
Yael Shammai ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Zinc Homeostasis ◽  
Healthy Population ◽  
Missense Mutations ◽  
Protein Alignment ◽  
Loss Of Function ◽  
Intracellular Zinc ◽  
Dismal Prognosis ◽  
Zinc Levels ◽  
And Function

Abstract Zinc is vital for the structure and function of ~3000 human proteins and hence plays key physiological roles. Consequently, impaired zinc homeostasis is associated with various human diseases including cancer. Intracellular zinc levels are tightly regulated by two families of zinc transporters: ZIPs and ZnTs; ZIPs import zinc into the cytosol from the extracellular milieu, or from the lumen of organelles into the cytoplasm. In contrast, the vast majority of ZnTs compartmentalize zinc within organelles, whereas the ubiquitously expressed ZnT1 is the sole zinc exporter. Herein, we explored the hypothesis that qualitative and quantitative alterations in ZnT1 activity impair cellular zinc homeostasis in cancer. Towards this end, we first used bioinformatics to analyze inactivating mutations in ZIPs and ZNTs, catalogued in the COSMIC and gnomAD databases, representing tumor specimens and healthy population controls, respectively. ZnT1, ZnT10, ZIP8, and ZIP10 showed extremely high rates of loss of function mutations in cancer as compared to healthy controls. Analysis of the putative functional impact of missense mutations in ZnT1-ZnT10 and ZIP1-ZIP14, using homologous protein alignment and structural predictions, revealed that ZnT1 displays a markedly increased frequency of predicted functionally deleterious mutations in malignant tumors, as compared to a healthy population. Furthermore, examination of ZnT1 expression in 30 cancer types in the TCGA database revealed five tumor types with significant ZnT1 overexpression, which predicted dismal prognosis for cancer patient survival. Novel functional zinc transport assays, which allowed for the indirect measurement of cytosolic zinc levels, established that wild type ZnT1 overexpression results in low intracellular zinc levels. In contrast, overexpression of predicted deleterious ZnT1 missense mutations did not reduce intracellular zinc levels, validating eight missense mutations as loss of function (LoF) mutations. Thus, alterations in ZnT1 expression and LoF mutations in ZnT1 provide a molecular mechanism for impaired zinc homeostasis in cancer formation and/or progression.

scholarly journals Cyclometalated iridium–BODIPY ratiometric O2 sensors

2019 ◽  
Vol 10 (19) ◽  
pp. 5124-5132 ◽  
Author(s):  
Ku Sun Choung ◽  
Karen Marroquin ◽  
Thomas S. Teets
Keyword(s):  
Molecular Oxygen ◽  
Simple Strategy ◽  
Ratiometric Sensors

Cyclometalated iridium–BODIPY conjugates are prepared by a simple strategy and are effective ratiometric sensors for molecular oxygen.

Zinc homeostatic proteins in the CNS are regulated by crosstalk between extracellular and intracellular zinc

2010 ◽  
Vol 224 (3) ◽  
pp. 567-574 ◽  
Author(s):  
Natalya Karol ◽  
Claude Brodski ◽  
Yuval Bibi ◽  
Tehila Kaisman ◽  
Michal Forberg ◽  
...  
Keyword(s):  
Intracellular Zinc

scholarly journals B cell activation and proliferation increase intracellular zinc levels

2019 ◽  
Vol 64 ◽  
pp. 72-79 ◽  
Author(s):  
Johanna Ollig ◽  
Veronika Kloubert ◽  
Kathryn M. Taylor ◽  
Lothar Rink
Keyword(s):  
B Cell ◽  
Cell Activation ◽  
B Cell Activation ◽  
Intracellular Zinc ◽  
Zinc Levels

scholarly journals ZIP7-Mediated Intracellular Zinc Transport Contributes to Aberrant Growth Factor Signaling in Antihormone-Resistant Breast Cancer Cells

Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 4912-4920 ◽  
Author(s):  
Kathryn M. Taylor ◽  
Petra Vichova ◽  
Nicola Jordan ◽  
Stephen Hiscox ◽  
Rhiannon Hendley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Growth Factor Signaling ◽  
Zinc Transport ◽  
Intracellular Zinc

scholarly journals Fluorescent chemosensors for metal ions based on 3-(2-benzoxazol-5-yl)alanine skeleton

2010 ◽  
Vol 8 (3) ◽  
pp. 674-686 ◽  
Author(s):  
Magda Milewska ◽  
Katarzyna Guzow ◽  
Wiesław Wiczk
Keyword(s):  
Steady State ◽  
Fluorescence Spectroscopy ◽  
Metal Ions ◽  
Ground State ◽  
Transition Metal Ions ◽  
Fluorescent Chemosensors ◽  
Time Resolved Fluorescence ◽  
Absorption Bands ◽  
Time Resolved ◽  
Ratiometric Sensors

AbstractThe ability of new chelate ligands, benzoxazol-5-yl-alanine derivatives substituted in position 2 by heteroaromatic substituent, to form complexes with selected metal ions in acetonitrile are studied by means of absorption and steady-state and time-resolved fluorescence spectroscopy. Among the ligands studied, only azaaromatic derivatives form stable complexes with transition metal ions in the ground state. Their absorption bands are bathochromically shifted enabling to use those ligands as ratiometric sensors. The fluorescence of each ligand is quenched by metal ions, however, in the presence of Cd(II) and Zn(II) ions a new red shifted emission band is observed.

Toxicity of increased intracellular zinc in colon cancer cells

2010 ◽  
Vol 196 ◽  
pp. S309
Author(s):  
E. Rudolf ◽  
S. John ◽  
T. Briatka ◽  
M. Červinka
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Colon Cancer Cells ◽  
Intracellular Zinc
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