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Nitroblue Tetrazolium
Published in Robert A. Greenwald, CRC Handbook of Methods for Oxygen Radical Research, 2018
Larry W. Oberley, Douglas R. Spitz
We have investigated these phenomena in great detail and have found that most of the effects are due to iron-sulfur proteins in cells.8 The bluish-purple color formation seems to be due to endogenous xanthine oxidase, while the low percentage inhibition is apparently caused by Fe-S proteins in the mitochondria. Both effects appear to be due to electron or oxygen free radical leakage from the Fe-S sites. Both effects are inhibited by thenoyltrifluoroacetone, bathophenanthrolinedisulfonic acid, disodium salt (4,7-diphenyl-1,10-phenanthrolinedisulfonic acid), and bathocuproinedisulfonic acid, disodium salt (2,9-dimethyl-4,7-diphenyl-1,10-phenanthrolinedisulfonic acid). We have found bathocuproine to be the most effective and easiest to use inhibitor. All of these compounds will precipitate when placed in the standard assay, so bovine serum albumin (BSA) must be used to keep the compounds in solution.
Copper-Thiolate Proteins (Metallothioneins)
Published in René Lontie, Copper Proteins and Copper Enzymes, 1984
Weser Ulrich, Hartmann Hans-Jürgen
Evolutionarily-seen sulfur has to be listed with the very early liganding species. Exclusive metal-sulfur coordination is found in iron-sulfur proteins, the noncatalytic zinc-binding center of alcohol dehydrogenase, and in the metallothioneins (MT’s), including copper-thionein. Iron-sulfur proteins actively participate in electron transport. At present the biological role of the other two classes of metal-containing proteins is unknown. The control of the levels of biochemically active metals, including Zn or Cu, could be the attractive function of the MT’s. The noncatalytical zinc-thiolate center of alcohol dehydrogenase might be an evolutionary precursor leading to the catalytic zinc center where mixed ligands histidine and cysteine are coordinated. Furthermore, copper coordination in the blue copper proteins is known to be at least to one or more sulfur moieties. This is an attempt to summarize the pertinent data on MT’s with special emphasis on the copper-thioneins.
A novel treatment strategy to prevent Parkinson’s disease: focus on iron regulatory protein 1 (IRP1)
Published in International Journal of Neuroscience, 2023
Thomas M. Berry, Ahmed A. Moustafa
Rotenone inhibits complex I of the electron transport chain by dysregulating iron-sulfur clusters of complex I [84]. Rotenone increases IRP1 and decreases activity of ACO1 [85]. Silencing of IRP1 protects cells from death induced by complex I inhibition [78]. Upon gaining an iron-sulfur cluster due to increases in iron IRP1 becomes aconitase 1 [86]. The goal of supplemental iron would be constant absorption of iron, constant systematic levels of iron and tight iron utilization. Hemoglobin levels could be misleading as to the status of iron-sulfur proteins. Heme is not an iron-sulfur protein. Heme proteins could be normal is PD while iron-sulfur proteins could be dysregulated. In Friedreich’s ataxia iron-sulfur cluster formation is dysregulated, however, hemoglobin levels are normal [87].
Decreased serum ferritin may be associated with increased restless legs syndrome in Parkinson’s disease (PD): a meta-analysis for the diagnosis of RLS in PD patients
Published in International Journal of Neuroscience, 2019
Kelu Li, Bin Liu, Fang Wang, Jianjian Bao, Chongmin Wu, Xiaodong Huang, Fayun Hu, Zhong Xu, Hui Ren, Xinglong Yang
Total iron and ferritin levels in the substantia nigra appear to increase with disease severity in PD. Histopathological studies and autopsy results of PD patients have indicated substantial amount of iron deposition in the substantia nigra, with iron ion content 225% higher and total iron content 25–100% higher than levels in individuals without PD [23,49], consistent with studies based on magnetic resonance imaging [50] and cerebral parenchyma ultrasound [51]. Iron deposition within the substantia nigra may lead to a vicious cycle of oxidative stress by increasing the amount of free iron via release of iron from ferritin, hemoglobin and iron–sulfur protein. This increase in free iron may induce progressive dopamine neurodegeneration and neuroinflammation, which exacerbate motor symptoms [31,52]. Conversely, RLS is characterized by reduced iron accumulation in the substantia nigra, based on magnetic resonance imaging [53] and cerebral parenchyma ultrasound [51]. One study found reduced levels of L- and H-ferritin subunits in RLS patients, suggesting chronic, active iron insufficiency [54]. And the level of low iron is positively related to the severity of RLS, which is thought to be the cause of worsening RLS symptoms at night [24]. In addition, the iron deficit correlates positively with RLS severity, and since pioneering work in 1953 [55], iron therapy has become a preferred treatment option for RLS patients [56].
Single-cell analysis reveals immune modulation and metabolic switch in tumor-draining lymph nodes
Published in OncoImmunology, 2020
Yen-Liang Li, Chung-Hsing Chen, Jing-Yi Chen, You-Syuan Lai, Shao-Chun Wang, Shih-Sheng Jiang, Wen-Chun Hung
Based on relatively stringent criteria to remove low-quality cells, a total of 98 FRCs were identified using the expression of marker gene Vim and these cells were classified into 4 subclusers using SC3 Figure 5a. Based on GSVA, 18 hallmark pathways were significantly associated with transcriptional alterations between FRCs in TDLNs and those in naive LNs (q-value < 0.1; Figure 5c). Intriguingly, oxidative phosphorylation (OXPHOS) pathway and peroxisome pathway were among the top 3 significantly upregulated pathways in TDLNs. Several genes involved in OXPHOS were selected and their differential expression (p-value < 0.05) represented by violin plot were shown in Figure 5d. Among them, cytochrome c oxidase subunit 7 C (Cox7c), which catalyzes the electron transfer from reduced cytochrome c to oxygen, is a subunit of complex IV of mitochondrion; NADH dehydrogenase flavoprotein 2 (Ndufv2) is a subunit of complex I that catalyzes the transfer of electrons from NADH to ubiquinone; Ndufa4 functioning as a NADH dehydrogenase with oxidoreductase activity on complex I;52 Ubiquinol-cytochrome c reductase, complex III sub-unit XI (Uqcr11) may function as a binding factor for the iron-sulfur protein in complex III, which is ubiquitous expressed in human cells; Peroxiredoxin-5 (Prdx5) is a peroxidase that can use cytosolic or mitochondrial thioredoxins to reduce alkyl hydroperoxides or peroxynitrite. PRDX5 has been shown to be a cytoprotective antioxidant enzyme that inhibits endogenous or exogenous peroxide accumulation.53 Our data are consistent to previous finding that FRCs in TDLNs immediately downstream of tumors undergo an altered function of FRCs’ mitochondria;54 our analysis further suggested a significantly upregulated OXPHOS pathway activity in FRCs of TDLNs. We also summarized the genes differentially expressed in OXPHOS pathways annotated by KEGG database. Interestingly, among 47 upregulated mitochondrial genes encoding proteins of respiratory chain, 27 genes are from complex I, 1 complex II, 6 complex III, 9 complex IV, and 4 complex V Figure 6a. These observations suggested a massive ATP consumption and consequently possible DNA damage followed by OXPHOS may occur during tumor progression in the TDLNs. To validate the change of OXPHOS pathway, we investigated extracellular oxygen consumption rates (OCR) in FRCs treated with or without the conditioned media of 4T1 mouse breast cancer cells or MMTV-PyMT cancer cells. Significant increase of OCR was found in the FRCs treated with the conditioned media of breast cancer cells Figure 6c.