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Copper deficiency has been reported to be associated withdecreased cytochrome c oxidase activity, whichin turn may be responsible for theobserved mitochondrial impairment and cardiac failure. We isolatedmito-chondriafrom hearts of copper-deficient rats: cytochrome c oxidase activity was found to be lowerthan incopper-adequate mitochondria. The residual activity paralleled coppercontent of mitochondria...
The induction of apoptotic cell death by cadmium was investigated in eight mammalian cell lines. Great differences in the cytotoxicity of cadmium were found with different cell lines: Rat C6 glioma cells turned out to be most sensitive with an IC50-value of 0.7 μM, while human A549 adenocarcinoma cells were relatively resistant with an IC50-value of 164 μM CdCl2. The mode of cadmium-induced cellular...
Central to oxidative damage in Alzheimer disease is the production of metal-catalyzed hydroxyl radicals that damage every category of macromolecule. Studies on redox-competent copper and iron indicate that redox activity in Alzheimer disease resides exclusively within the cytosol of vulnerable neurons and that chelation with deferoxamine or DTPA removes this activity. We have also found that while...
The kinetics of the early subcellular distribution of cadmium (Cd) was characterized in primary cultures of rat hepatocytes exposed to 10, 50 and 100 μM Cd in a serum-free WME medium for 10, 30 or 60 min. Our results demonstrate a time- and concentration-dependent increase in Cd content with the highest metal concentration measured in the cytosol, whereas the lowest was observed in the mitochondria...
Transition metal ions are required for many aspects of mitochondrial physiology. Copper, iron, manganese and zinc are cofactors in metalloenzymes and metalloproteins within the organelle. Little is known how cells maintain optimal pools of these metal ions for mitochondrial function. This review documents the available literature on mitochondrial metal ion pools and protein metallation reactions....
The effects of potassium tellurite on growth and survival of rho+ and rho0Saccharomyces cerevisiae strains were investigated. Both rho+ and rho0 strains grew on a fermentable carbon source with up to 1.2 mM K2TeO3, while rho+ yeast cells grown on a non-fermentable carbon source were inhibited at tellurite levels as low as 50 μM suggesting that this metalloid specifically inhibited mitochondrial functions...
European eels are dangerously threatened with extinction. Recent advances tend to show that pollution could, in addition to other already identified factors, contribute to this drama. In a previous report, cadmium (Cd) pre-exposure was found to strongly stimulate the pituitary-liver-gonad axis of maturing female silver eels, leading, lastly, to oocytes atresia and eels mortality. The present work...
In order to explore the role of mitochondria in proliferation promotion and/or apoptosis induction of lanthanum, the mutual influences between La3+ and Ca2+ on mitochondrial permeability transition pore (PTP) opening were investigated with isolated mitochondria from rat liver. The experimental results revealed that La3+ influence the state of mitochondria in a concentration-dependent biphasic manner...
Increased intracellular free zinc concentrations are associated with activation of several stress signaling pathways, specific organelle injury and final cell death. In the present work we examined the involvement of mitochondria and lysosomes and their crosstalk in free zinc-induced cell demise. We report that treatment of cervical tumor Hep-2 cells with zinc pyrithione leads to an early appearance...
Mitochondria play an essential role in producing the energy required for seedling growth following imbibition. Heavy metals, such as cadmium impair mitochondrial functioning in part by altering redox regulation. The activities of two protein redox systems present in mitochondria, thioredoxin (Trx) and glutaredoxin (Grx), were analysed in the cotyledons and embryo of pea (Pisum sativum L.) germinating...
The role of copper in the toxicity of mutant copper-dependent enzyme superoxide dismutase (SOD1) found in patients affected with the familial form of amyotrophic lateral sclerosis (fALS) is widely debated. Here we report that treatment of human neuroblastoma cells SH-SY5Y with a specific copper chelator, triethylene tetramine (Trien) induces the decrease of intracellular copper level, paralleled by...
The Casiopeínas® are mixed chelate copper (II) complexes and promising antineoplastics agents against cancer cells and tumors in vitro and in vivo. However, the action mode of these compounds is poorly characterized. In this work the effect of the antineoplastic Casiopeína IIIEa on the metabolism and ultrastructure of the yeast Saccharomyces cerevisiae was investigated. Exposure of cells growing in...
Zinc is an essential trace element in cells. However, its high level in cytoplasm promotes activation of stress signaling pathways and may lead to cell death. In the present study we used Drosophila melanogaster blood cells (haemocytes), obtained from the third instar larvae, to study the effects of high concentrations of Zn2+ on programmed cell death (PCD). We analyzed the activity of caspases, the...
Iron acquired by cells is delivered to mitochondria for metabolic processing via pathways comprising undefined chemical forms. In order to assess cytosolic factors that affect those iron delivery pathways, we relied on microscopy and flow-cytometry for monitoring iron traffic in: (a) K562 erythroleukemia cells labeled with fluorescent metal-sensors targeted to either cytosol or mitochondria and responsive...
Organoseleno-compounds have been investigated for its beneficial effects against methylmercury toxicity. In this way, diphenyl diselenide (PhSe)2 was demonstrated to decrease Hg accumulation in mice, protect against MeHg-induced mitochondrial dysfunction, and protect against the overall toxicity of this metal. In the present study we aimed to investigate if co-treatment with (PhSe)2 and MeHg could...
Deregulated iron homeostasis is generally believed to be implicated in neurodegenerative diseases, including Parkinson’s disease. Nevertheless, it is not fully understood how iron overload can elicit neuronal cell damage. Here we examined mitochondrial reactive oxygen species (ROS) levels in human dopaminergic neuroblastoma SH-SY5Y cells upon iron exposure. A relatively high concentration of iron...
Cell-impermeant iron chelator desferrioxamine (DFO) can have access to organelles if appended to suitable vectors. Mitochondria are important targets for the treatment of iron overload-related neurodegenerative diseases. Triphenylphosphonium (TPP) is a delocalized lipophilic cation used to ferry molecules to mitochondria. Here we report the synthesis and characterization of the conjugate TPP–DFO as...
First generation silver(I) phosphines have garnered much interest due to their vast structural diversity and promising anticancer activity. Increasing incidences of cancer, side-effects to chemotherapeutic agents and redevelopment of tumors due to resistance prompts the exploration of alternative compounds showing anticancer activity. This study revealed the effective induction of cell death by a...
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