Excess Of Copper Ions Research Articles

A copper missile-triggered power coalescence and death vortex within tumor cell mitochondria for synergistic cuproptosis/phototherapy/chemotherapy.

The importance of copper homeostasis in mitochondria and copper-triggered modality of mitochondrial cell death have been confirmed. However, the existing copper-based nanoplatforms are focused on synergistic therapies while the intracellular therapeutic targets are relatively scattered. Effective integration of all targets within mitochondria to generate power coalescence remains a challenge. Herein, we developed a novel copper-based delivery system to trigger power coalescence and death vortex within tumor cell mitochondria. Specifically, a mitochondrial targeting "copper missile" loaded with curcumin (termed as Cur@CuS-TPP-HA, CCTH) was designed for cuproptosis/phototherapy/chemotherapy synergistic anti-tumor therapy. Once the CCTH NPs are shuttled to the mitochondria, near-infrared (NIR) irradiation initiates the release of copper ions and curcumin for in situ drug accumulation in cancer cell mitochondria. An excess of copper ions and curcumin can activate cuproptosis and mitochondrial apoptosis pathways, respectively. When combined, they can cause an increase in reactive oxygen species (ROS), damage to mitochondrial DNA (mt-DNA), and a decrease in energy supply, thereby leading to a "vicious circle" of mitochondrial damage that further enhances the tumor-killing efficacy. As a consequence, this "copper missile" exhibits advanced anti-tumor effects as verified through in vitro assessments and in vivo evaluations using the 4T1 breast tumor model, providing a promising approach for cuproptosis-based synergistic anti-tumor therapy.

Изменение спектра фенольных соединений циннии при избытке ионов меди в субстрате

Changes in the qualitative and quantitative composition of phenolic compounds in response to adverse environmental influences are actively studied, primarily in connection with the antioxidant function of these compounds. However, phenolic compounds such as phenylpropanoids are known to be involved in cell wall lignification. Lignin deposition is not only a natural process for the formation of secondary cell walls, but it is also often considered as a non-specific reaction of plants under stress conditions. However, changes in the content and composition of phenolic compounds during lignification in response to stressors have not been studied enough. Previously, we showed a decrease in the amount of phenolic compounds in response to the action of copper ions, but the question remained whether they are spent on the lignification process or on the quenching of reactive oxygen species. In this regard, the purpose of this work was to identify changes in the amount and composition of phenolic compounds of different polarity in the axial organs of zinnia when grown in a medium with an excess of copper ions. It was shown that under stress caused by copper ions (watering the substrate with a solution of 200 μM copper sulfate), in the roots of 40-day-old zinnia plants, the total content of phenolic compounds did not change significantly. At the same time, the content of fractions soluble in diethyl ether (hydroxycinnamic acids) and ethyl acetate (aglycones of flavonoids and coumarins) decreased, which may indicate the use of phenylpropanoids for additional synthesis of lignin, and flavonoids for antioxidant reactions under stress. In the hypocotyl, the content of hydroxycinnamic acids slightly increased, while in the first internode it did not change. The main part of phenolic compounds in all organs, both in control stressed plants, belonged to the fraction of glycosylated derivatives. At the same time, among this derivates the content of water-soluble phenols increased in the experimental plants in all organs. Thus, under the stress caused by copper ions, the composition and number of phenolic compounds changed.

Selective Detection of Cu+ Ions in Live Cells via Fluorescence Lifetime Imaging Microscopy.

Copper is an essential trace element in living organisms with its levels and localisation being carefully managed by the cellular machinery. However, if misregulated, deficiency or excess of copper ions can lead to several diseases. Therefore, it is important to have reliable methods to detect, monitor and visualise this metal in cells. Herein we report a new optical probe based on BODIPY, which shows a switch‐on in its fluorescence intensity upon binding to copper(I), but not in the presence of high concentration of other physiologically relevant metal ions. More interestingly, binding to copper(I) leads to significant changes in the fluorescence lifetime of the new probe, which can be used to visualize copper(I) pools in lysosomes of live cells via fluorescence lifetime imaging microscopy (FLIM).

Selective Detection of Cu+ Ions in Live Cells via Fluorescence Lifetime Imaging Microscopy

AbstractCopper is an essential trace element in living organisms with its levels and localisation being carefully managed by the cellular machinery. However, if misregulated, deficiency or excess of copper ions can lead to several diseases. Therefore, it is important to have reliable methods to detect, monitor and visualise this metal in cells. Herein we report a new optical probe based on BODIPY, which shows a switch‐on in its fluorescence intensity upon binding to copper(I), but not in the presence of high concentration of other physiologically relevant metal ions. More interestingly, binding to copper(I) leads to significant changes in the fluorescence lifetime of the new probe, which can be used to visualize copper(I) pools in lysosomes of live cells via fluorescence lifetime imaging microscopy (FLIM).

The molecular mechanisms of copper metabolism and its roles in human diseases.

Copper is an essential element in cells; it can act as either a recipient or a donor of electrons, participating in various reactions. However, an excess of copper ions in cells is detrimental as these copper ions can generate free radicals and increase oxidative stress. In multicellular organisms, copper metabolism involves uptake, distribution, sequestration, and excretion, at both the cellular and systemic levels. Mammalian enterocytes take in bioavailable copper ions from the diet in a Ctr1-dependent manner. After incorporation, cuprous ions are delivered to ATP7A, which pumps Cu+ from enterocytes into the blood. Copper ions arrive at the liver through the portal vein and are incorporated into hepatocytes by Ctr1. Then, Cu+ can be secreted into the bile or the blood via the Atox1/ATP7B/ceruloplasmin route. In the bloodstream, this micronutrient can reach peripheral tissues and is again incorporated by Ctr1. In peripheral tissue cells, cuprous ions are either sequestrated by molecules such as metallothioneins or targeted to utilization pathways by chaperons such as Atox1, Cox17, and CCS. Copper metabolism must be tightly controlled in order to achieve homeostasis and avoid disorders. A hereditary or acquired copper unbalance, including deficiency, overload, or misdistribution, may cause or aggravate certain diseases such as Menkes disease, Wilson disease, neurodegenerative diseases, anemia, metabolic syndrome, cardiovascular diseases, and cancer. A full understanding of copper metabolism and its roles in diseases underlies the identification of novel effective therapies for such diseases.

Kinetics based determination of trace amounts of silver at the excess of copper ions

The determination of silver traces, based on the catalytic action of Ag + ions in the oxidation of salicylic acid by persulfate in the presence of 2,2′-dipyridyl as an activator, has been elaborated. The influence of several parameters, such as temperature, pH, salicylic acid concentration, persulfate concentration and 2,2′-dipyridyl concentration on the course of reaction has been investigated. The activation energies of the catalyzed (30.79 kJ mol −1) and non-catalyzed (44.77 kJ mol −1) processes were determined. Optimum conditions for the silver determination in the range of 4.3–38.8 ng cm −3 were established. The proposed method is more sensitive than atomic absorption spectrometry (AAS). The detection limit was 0.38 ng cm −3, so it was at least three orders of magnitude lower than that for the AAS method. The described method was used in the determination of the silver content in samples containing excess of copper and/or sulfate ions at concentrations of 8×10 −6–2.4×10 −2 M. The sulfate ions do not disturb the course of the reaction. The results of the determination of silver in a copper sheet by the proposed method were compared with the results of the analysis performed by AAS.

Bioaccumulation du cuivre chez littorina littorea (L.) (Gastéropode prosobranche): signification physiologique et écologique

A study of Littorina littorea (L.) samples, collected in their natural environment of experimentally intoxicated in aquariums, shows copper in four types of cells, as revealed by histochemical reaction on thin sections, X-ray and Raman spectrometries or secondary ion emission analysis. The excretory cells of conjunctive tissue (as defined by Cuénot), are dispersed in the vesicular conjunctive tissue and myocardium, and their general appearance resemble podocytes. In these cells, copper is precipitated in the form of clusters of CuS needles inside the lysosomes. The accumulation of copper sulphide increases with the age of the animals and is independent of the environment. It is interpreted as being result of hemocyanin degradation. The perivascular cells surround the aorta and arteries. Here copper is found inside the sphero-crystals, associated with certain other minerals, principally Mg and Ca. Intoxication by copper ions results in a deposit at the periphery of these sphero-crystals. The “digestive cells” of the hepatopancreas are the third type. Copper in a still non-determined form, though known to be in an unstable state, may be found along the lateral and basal boundaries of these cells. These aspects have been observed only in rare organisms collected from polluted zones. The fourth type of cell is the axial conjunctive cells of renal lamellae. Here copper is present in a dispersed pattern overlying that of the sulphydrilated proteins. Maxima concentrations have been found in animals coming from polluted zones, but an excess of copper ions in the environment has no effect on them. Intoxication by copper sulphate causes branchial lesions. Progressive accumulation of copper sulphide, independent of the environment, makes the Littorina an unreliable biological indicator of pollution by copper.

Complexing Capacity of Natural Water--Its Significance and Measurement

Most of the trace metals in natural waters are believed to exist in complexed or chelated forms with the miscellaneous organic ligands of both natural and pollutants origin which regulate the availability of these metals in the system (1–5). Such a mechanism maintains a reservoir of metals ready for biological uses. The abundance of complexing ligands in a body of water thus determines the complexing capacity of the water and hence its regulating capability. The measurement of complexing capacity will add a new parameter to the chemistry of trace metals in the aquatic environment, especially in areas of biological uptake and toxicological studies (6,7). Such information is also pertinent in bioassay work where the knowledge of the possible forms of the metals after being added to a system is important. The measurement of complexing capacity of a water sample is based on the amount of copper ion being complexed by the organic ligands through direct complexation and/or displacement reaction. It is done by spiking several aliquots of a sample with increasing amounts of a copper solution. Then the uncomplexed copper is measured by a differential pulse anodic stripping voltammetric technique (8,9). After the complexing ligands in the sample have been saturated with copper, the peak current of free copper will increase linearly with the amount of the copper spikes. By extrapolating this linear curve back to zero peak current, the intercept on the X-axis represents the complexing capacity of the water expressed as equivalents of μ mole Cu/l. As the differential pulse anodic stripping voltammetry measurement of “free” copper is carried out in a system containing excess of copper ions, the peak current thus obtained represents the concentration of “free” copper. The amount of copper plated out from the labile complexes, if any, becomes insignificant (8). Table I illustrates some complexing capacity values of natural waters. Preliminary work on the chemical characterization of the complexing substances in lake water, using ultra-filtration techniques, indicated that these complexing compounds fall in an arbitrary molecular range of 1,000–10,000. Further investigations are being carried out to isolate and to characterize this fraction (9). The significance of complexing capacity of water on the effect and toxicity of copper ion on algal photosynthesis has also been investigated (10) using the 14C uptake technique with lake waters of different complexing capacity and with the original plankton species. It was observed that complexing capacity of a water body does not imply that the equivalent amount of copper can be taken up (masked) by the water without affecting the plankton growth, although it has been a recognized fact that chelating agents such as NTA, EDTA can mask up the toxicity of copper. Further studies are being carried out to find out the quantitative biological meaning of complexing capacity. The chemical and biological aspects of the problem must go hand in hand.