Metals in Neurobiology: Probing Their Chemistry and Biology with Molecular Imaging

Que, Emily L.; Domaille, Dylan W.; Chang, Christopher J.

doi:10.1021/cr078203u

Cited by 1,910 publications

(1,156 citation statements)

References 470 publications

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“…The development of innovative fluorescent imaging probes has revolutionized cell biology, allowing localization and dynamic monitoring of cellular metabolite and inorganic ion pools 15,16,[24][25][26][27][28][29] . A significant bottleneck in the emerging field of H 2 S/aqueous sulphide signalling is the absence of technology for effective in vivo detection and imaging, a problem that is exacerbated by the high intracellular thiol concentration.…”

Section: Discussionmentioning

confidence: 99%

Selective fluorescent probes for live-cell monitoring of sulphide

et al. 2011

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Aqueous sulphides, including hydrogen sulphide, have important roles in biological signalling and metabolic processes. Here we develop a selective sulphide-trapping strategy involving sulphide addition to an aldehyde; the resulting hemithioacetal undergoes a michael addition with an adjacent unsaturated acrylate ester to form a thioacetal at neutral pH in aqueous solution. Employing this new strategy, two sulphide-selective fluorescent probes, sFP-1 and sFP-2, were synthesized on the basis of two different fluorophore templates. These probes exhibit an excellent fluorescence increase and an emission maximum shift (sFP-1) in response to na 2 s and H 2 s in a high thiol background as found under physiological conditions. We show the utility of the probes for the selective detection of sulphides, and the capacity of our probes to monitor enzymatic H 2 s biogenesis and image free sulphide in living cells.

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Section: Discussionmentioning

confidence: 99%

Selective fluorescent probes for live-cell monitoring of sulphide

et al. 2011

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“…However, there is a lack of a definitive study that clearly establishes within which cellular compartment insulin hydrolysis occurs [75]. IDE is primarily cytosolic but it was also found in peroxisomes [76], endosomes [77], mitochondria [78] and plasma membranes [79]; however, since neither of these compartments is believed to contain insulin, they cannot be the site of its catabolism. Moreover, it is known that metals are essential for many metabolic processes and their homeostasis is crucial in every living cell.…”

Section: Discussionmentioning

confidence: 99%

Metal ions affect insulin-degrading enzyme activity

Grasso

Salomone

Tundo

et al. 2012

Journal of Inorganic Biochemistry

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Insulin degradation is a finely tuned process that plays a major role in controlling insulin action and most evidence supports IDE (insulin-degrading enzyme) as the primary degradative agent. However, the biomolecular mechanisms involved in the interaction between IDE and its substrates are often obscure, rendering the specific enzyme activity quite difficult to target. On the other hand, biometals, such as copper, aluminum and zinc, have an important role in pathological conditions such as Alzheimer's disease or diabetes mellitus. The metabolic disorders connected with the latter lead to some metallostasis alterations in the human body and many studies point at a high level of interdependence between diabetes and several cations. We have previously reported (Grasso et al., Chem. Eur. J. 17 (2011) 2752-2762) that IDE activity toward Aβ peptides can be modulated by metal ions. Here, we have investigated the effects of different metal ions on the IDE proteolytic activity toward insulin as well as a designed peptide comprising a portion of the insulin B chain (B20-30), which has a very low affinity for metal ions. The results obtained by different experimental techniques clearly show that IDE is irreversibly inhibited by copper(I) but is still able to process its substrates when it is bound to copper(II).

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“…Active cells require iron as a key component of enzymes involved in oxygen transport and metabolism. 63 Most iron is chelated and stored in the protein ferritin as Fe 3+ , 23,63 which shortens water proton T 1 and T 2 relaxation times. 23,64 Accordingly, several studies reported T 1 and T 2 effects as a function of iron content 10,[23][24][25]65 in the human brain, with concentration in the globus pallidus (GP) among the highest.…”

Section: Nerve Cellsmentioning

confidence: 99%

“…70 Proteins involved in iron management, i.e., ferritin and transferrin, are also expressed in abundance within oligodendrocytes. 63,70 Accordingly, layer IV in the human visual cortex, well known as the stria of Gennari for its pronounced myelination, can be clearly delineated by MR imaging 1,2 based on a locally increased T 2 relaxation rate. The effect is supposed to be caused by iron rather than macromolecules because the corresponding ex vivo MR imaging contrast 68,71 is better co-localized with the iron distribution than with myelin or cell assemblies and is reduced after chemical extraction of tissue iron.…”

Section: Oligodendrocytesmentioning

confidence: 99%

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

2016

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This article provides an overview of in vivo magnetic resonance (MR) imaging contrasts obtained for mammalian brain in relation to histological knowledge. Emphasis is paid to the (1) significance of high spatial resolution for the optimization of T 1 , T 2 , and magnetization transfer contrast, (2) use of exogenous extra-and intracellular contrast agents for validating endogenous contrast sources, and (3) histological structures and biochemical compounds underlying these contrasts and (4) their relevance to neuroradiology. Comparisons between MR imaging at subnanoliter resolution and histological data indicate that (a) myelin sheaths, (b) nerve cells, and (c) the neuropil are most responsible for observed MR imaging contrasts, while (a) diamagnetic macromolecules, (b) intracellular paramagnetic ions, and (c) extracellular free water, respectively, emerge as the dominant factors. Enhanced relaxation rates due to paramagnetic ions, such as iron and manganese, have been observed for oligodendrocytes, astrocytes, microglia, and blood cells in the brain as well as for nerve cells. Taken together, a plethora of observations suggests that the delineation of specific structures in high-resolution MR imaging of mammalian brain and the absence of corresponding contrasts in MR imaging of the human brain do not necessarily indicate differences between species but may be explained by partial volume effects. Second, paramagnetic ions are required in active cells in vivo which may reduce the magnetization transfer ratio in the brain through accelerated T 1 recovery. Third, reductions of the magnetization transfer ratio may be more sensitive to a particular pathological condition, such as astrocytosis, microglial activation, inflammation, and demyelination, than changes in relaxation. This is because the simultaneous occurrence of increased paramagnetic ions (i.e., shorter relaxation times) and increased free water (i.e., longer relaxation times) may cancel T 1 or T 2 effects, whereas both processes reduce the magnetization transfer ratio.

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Metals in Neurobiology: Probing Their Chemistry and Biology with Molecular Imaging

Cited by 1,910 publications

References 470 publications

Selective fluorescent probes for live-cell monitoring of sulphide

Selective fluorescent probes for live-cell monitoring of sulphide

Metal ions affect insulin-degrading enzyme activity

<i>In Vivo</i> Brain MR Imaging at Subnanoliter Resolution: Contrast and Histology

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