Journal of inorganic biochemistry
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Zinc can play a pathophysiological role in several diseases and can interfere in key processes of microbial growth. This evidence justifies the efforts in applying Zinc ionophores to restore Zinc homeostasis and treat bacterial/viral infections such as coronavirus diseases. Zinc ionophores increase the intracellular concentration of Zinc ions causing significant biological effects. This review provides, for the first time, an overview of the applications of the main Zinc ionophores in Zinc deficiency, infectious diseases, and in cancer, discussing the pharmacological and coordination properties of the Zinc ionophores.
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The ability to sense and adapt to changes in pO2 is crucial for basic metabolism in most organisms, leading to elaborate pathways for sensing hypoxia (low pO2). This review focuses on the mechanisms utilized by mammals and bacteria to sense hypoxia. While responses to acute hypoxia in mammalian tissues lead to altered vascular tension, the molecular mechanism of signal transduction is not well understood. ⋯ The sensing modality for bacterial O2-sensors is either via altered DNA binding affinity of the sensory protein, or else due to the actions of a two-component signaling cascade. Emerging data suggests that proteins containing a hemerythrin-domain, such as FBXL5, may serve to connect iron sensing to O2-sensing in both bacteria and humans. As specific molecular machinery becomes identified, these hypoxia sensing pathways present therapeutic targets for diseases including ischemia, cancer, or bacterial infection.
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The Root effect describes an extreme pH sensitivity expressed in the hemoglobins of certain fish, in which it plays a unique physiological role. This review describes our general understanding of the effect of protons on the oxygen binding properties of hemoglobin and the particular properties which characterize Root effect proteins. The development of our understanding of the molecular origins of this effect is outlined and the role played by our ever expanding knowledge of protein structure is highlighted. The present state of our knowledge is detailed.
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Review
Platinum neurotoxicity: clinical profiles, experimental models and neuroprotective approaches.
This paper reviews the neurotoxic side-effects associated with platinum drugs, experimental approaches to studying this toxicity and attempts to use neuroprotective agents in conjunction with platinum drugs. Platinum drugs differ in their neurotoxicity profiles in patients. ⋯ Animal models, primary cultures of dorsal root ganglia neurons and tumour cell-lines of neuronal origin are being used in attempts to identify potential treatments for platinum-induced neurotoxicity. To date, clinical trials have been hampered by the poor tolerance of neuroprotective treatments and failure to achieve reversal of platinum drug neurotoxicity with thiols, neurotrophic factors or calcium channel blockers.