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Chemical Factors
Published in Michael J. Kennish, Ecology of Estuaries Physical and Chemical Aspects, 2019
While some trace metals are essential to nutrition and growth of marine organisms inhabiting coastal and estuarine waters (e.g., Co, Cu, Mn, and Zn), others are potentially toxic (e.g., Ag, Cd, Cr, Hg, and Pb).131 As imparted by Engel and Brouwer,131 trace metals such as cadmium, copper, mercury, and zinc are bound to metallothioneins in most organisms. Metallothionein, a low-molecular-weight, sulfur-containing metal-binding protein, and metallothionein-like proteins have been implicated in trace-metal detoxification processes. Engel and Brouwer131 confirm the involvement of metallothionein in the sequestration of elevated levels of trace metals, but hypothesize that their primary function is in regulating normal metal metabolism of marine and estuarine organisms.
Kinetics and Metabolism
Published in Lars Friberg, Tord Kjellström, Carl-Gustaf Elinder, Gunnar F. Nordberg, Cadmium and Health: A Toxicological and Epidemiological Appraisal, 2019
Gunnar F. Nordberg, Tord Kjellström, Monica Nordberg
Garty et al.99 in their studies of blood from rats injected with 109Cd found, using gel chromatography, that a considerable proportion of the cadmium in blood was bound to blood cell ghosts (membranes) and that cadmium in the hemolysate was bound to a protein similar in size to metallothionein. Ion-exchange chromatography of the cadmium-binding protein disclosed properties different from those of metallothionein from rat liver and the authors suggested that cadmium might induce a metal-binding protein (different from metallothionein) in the ghosts (membranes) of immature nucleated erythrocytes in the bone marrow and that a delay of 60 hr is needed for this protein-bound cadmium to reach the circulation.
Metals
Published in Frank A. Barile, Barile’s Clinical Toxicology, 2019
Anirudh J. Chintalapati, Frank A. Barile
Zn interacts with other physiologically important metals. Zn and Cu have a reciprocal relationship—that is, a high intake of Zn precipitates Cu depletion. The metal also interacts with Ca and is necessary for proper bone calcification. Cd competes with Zn for binding to sulfhydryl groups present on macromolecules. It also induces the metal-binding protein, metallothionein, which is involved in the absorption, metabolism, and storage of both essential and nonessential metals. Recently, the aggregation of ionic zinc and copper in cortical glutamatergic synapses has been implicated in modulating the response of the NMDA receptor and the vulnerability of amyloid-β to abnormal interaction with these metal ions, leading to a possible explanation for the mechanism underlying Alzheimer’s disease. This metals hypothesis of Alzheimer’s disease is based on observations of the precipitation of amyloid-β by Zn and its radicalization by Cu. Interestingly, both metals are markedly enriched in plaques.
Hepatotoxic effect of lead and hepatoprotective effect of Hydrilla verticillata on hepatic transcriptional and physiological response in edible fish Labeo rohita
Published in Drug and Chemical Toxicology, 2022
Pandi Prabha S., Johanna Rajkumar, Karthik C.
One of the major assessments of metal toxicology on molecular biology is the binding of proteins to the metals (Zalups and Koropatnick 2000). MTs are low‐molecular‐weight metal binding proteins and play a vital role in protection against heavy metal toxicity. MTs are known to be proteins involved in protection against oxidative stress and important factors in apoptosis. Increased MT synthesis is associated with increased capacity for binding metals such as lead, copper, zinc and cadmium, as well as protection against metal toxicity. Kovendan et al. (2013) reported that lead binds to MT protein, gets absorbed and transported to the liver, where it induces the synthesis of MTs. Hsp70 mRNA transcription is regulated by physiological factors, such as hormones and cytokines, or by environmental factors, such as xenobiotics or physical parameters (Safari et al.2014). The Hsp70 family consists of a group of related molecular chaperones that respond to cellular stress. The stimulation of mRNA levels of Hsp70 gene in liver in lead toxicity may be a defence mechanism to protect the organism from oxidative stress (Ozkan-Yılmaz et al.2015).
Targetting ferroptosis for blood cell-related diseases
Published in Journal of Drug Targeting, 2022
Zhe Chen, Jinyong Jiang, Nian Fu, Linxi Chen
Hepatic ferroptosis damages the development of red blood cells and erythropoiesis. Serum-abundant metal-binding protein transferrin is encoded by the Trf gene. Evidence shows that specifically knockouting hepatic transferrin (Trf-LKO) can increase hepatic iron overload and due to hepatic metal transporter ZIP14 (SLC39A14) which can significantly transfer iron into hepatocyte in mice [23]. Systemic hepatic iron overload induces ferroptosis and affects simultaneous severe iron demand in the erythroid system, thus impairing erythropoiesis. In Trf-LKO mice, hepatic iron overload is mainly due to hepatic metal transporter ZIP14 (SLC39A14) which can significantly transfer iron into hepatocyte. Additionally, patients with low level of serum transferrin and hepatic transferrin show the high level of hepatic iron and lipid peroxidation. The above-mentioned descriptions hint that ferroptosis damages systemic iron homeostasis and erythropoiesis.
Transcription profiling of cadmium-exposed livers reveals alteration of lipid metabolism and predisposition to hepatic steatosis
Published in Xenobiotica, 2021
Chenghui Ren, Longfei Ren, Jun Yan, Zhongtian Bai, Lei Zhang, Honglong Zhang, Ye Xie, Xun Li
Metallothionein is a low-molecular-weight (6–7 kDa) protein widely present in organisms. It is a metal-binding protein rich in metal and cysteine (Cys 20–30%), important for heavy metal detoxification (Cho et al.2008). A large number of sulfhydryl groups endow it with the function of chelating heavy metal ions and detoxifying heavy metals. At the same time, the ability of Mt to scavenge free radicals is significantly stronger than that of superoxide dismutase and glutathione. There are many reports about the detoxification effect of Mt on Cd. Milnerowicz et al. (2017) found that the expression of Mt in the liver and kidney of rats was significantly increased after exposure to Cd. Feng et al. (2018) pointed out that Mt had a protective effect on oxidative damage of grass carp liver caused by Cd. In our results, the multiple subtypes of Mt found in the liver (Mt1m, Mt2A, and Mt1) were involved in heavy metal detoxification after Cd exposure, and their expression levels were found to have increased significantly.