China
Africa
Explore chapters and articles related to this topic
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].
Mechanistic studies on the drug metabolism and toxicity originating from cytochromes P450
Published in Drug Metabolism Reviews, 2020
Chaitanya K. Jaladanki, Anuj Gahlawat, Gajanan Rathod, Hardeep Sandhu, Kousar Jahan, Prasad V. Bharatam
During CYP450 mediated drug metabolism (Meunier et al. 2004; Shaik et al. 2010) (Figure 3), initially, the drug (R-H) binds to heme iron (Loew and Harris 2000) center and displaces a water molecule, and 1st reduction takes place (Shaik et al. 2005). The covalent bond formation takes place with molecular oxygen followed by 2nd reduction. From the catalytic cycle above, it is evident that a CYP450 cycle requires two electrons. In the biological system, CYP450 family does not accept direct electrons derived from NAD(P)H but their transfer occurs through the various redox proteins. These redox proteins can have one or two component shuttle system. (Paine et al. 2005; Waskell and Kim 2015) One component shuttle system involves a single membrane-bound enzyme i.e. NADPH cytochrome P450 reductase (CPR). While two component shuttle system involves a cascade of two different redox proteins and carried out in two ways: First type involves two proteins i.e. Adrenodoxin reductase and Adrenodoxin. Adrenodoxin reductase present in mitochondria of eukaryotic cell, which takes electrons/protons from NADPH via FAD cofactor and transfer an electron to Adrenodoxin (iron-sulfur protein), which further transfer to CYP450 catalytic cycle (Miller and Chunk 2016).Second type involves other two proteins i.e cytochrome b5 reductase and cytochrome b5. The cytochrome b5 can also take electron from CYP450 reductase. There are reports which suggest that in the cellular system, cytochrome b5 protein can transfer second electron faster than NADPH CYP450 reductase (Im and Waskell 2011; Manikandan and Nagini 2018).