Possible mechanisms underlying copper-induced damage in biological membranes leading to cellular toxicity

Letelier, María Eugenia; Lepe, Ana Maria; Faúndez, Mario; Salazar, Julia; Marín, Rigoberto; Aracena-Parks, Paula; Speisky, Hernán

doi:10.1016/j.cbi.2004.12.004

Cited by 213 publications

(135 citation statements)

References 29 publications

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…Since at normal temperature (25°C), p38-MAPK activation by copper is not mediated by oxidative factors, it could be suggested that this stimulation is possibly mediated by conformational changes in membrane proteins that participate in signal transduction pathways (Wu et al, 1999;Letelier et al, 2005). In addition, copper has been proposed to inhibit the activity of the antiporter Na + /K + -ATPase (Li et al, 1996;Handy et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Cu2+ and acute thermal stress induce protective eventsviathe p38-MAPK signalling pathway in the perfusedRana ridibundaheart

Gaitanaki

Pliatska

Σταθοπούλου

et al. 2007

Journal of Experimental Biology

View full text Add to dashboard Cite

SUMMARY In the present study, we investigated the induction of the p38-MAPK signalling pathway by copper, as exemplified by CuCl2, in the isolated perfused heart of the amphibian Rana ridibunda. We found that p38-MAPK phosphorylation by CuCl2 occurs in a dose-dependent manner, with maximum activation (8.73±1.43-fold relative to control values) attained by perfusion with 500 μmol l–1CuCl2 for 15 min, while this activation sustained even after 60 min of reperfusion with normal bicarbonate buffer. CuCl2 also induced the phosphorylation of the small heat shock protein 27 (Hsp27) in a p38-MAPK dependent manner, as revealed by experiments using the p38-MAPK inhibitor SB203580. p38-MAPK and Hsp27 phosphorylations were also strongly induced by hyperthermia (42°C), while the simultaneous use of hyperthermia and CuCl2 had a synergistic effect on p38-MAPK activation. Furthermore,perfusions with the potent antioxidant L-ascorbic acid (100 μmol l–1), the antioxidant enzymes catalase (CAT) (150 U ml–1) or superoxide dismutase (SOD) (30 U ml–1) in the presence of 500 μmol l–1CuCl2 did not attenuate the CuCl2-induced p38-MAPK activation, implying that at least the reactive oxygen species (ROS) scavenged by these agents are not implicated in this kinase activation. The p38-MAPK phosphorylation induced by the combined action of CuCl2 and hyperthermia was partially inhibited by catalase, indicating that hyperthermia possibly activates the kinase through the production of H2O2. Caspase-3, an effector protease of apoptosis,remained inactive in hearts perfused at normal or hyperthermic conditions, in the absence or presence of 500 μmol l–1 CuCl2. All the above results suggest that, in the amphibian Rana ridibundaheart, p38-MAPK activation by copper has a possible protective role through the small Hsp27.

show abstract

Section: Discussionmentioning

confidence: 99%

Cu2+ and acute thermal stress induce protective eventsviathe p38-MAPK signalling pathway in the perfusedRana ridibundaheart

Gaitanaki

Pliatska

Σταθοπούλου

et al. 2007

Journal of Experimental Biology

View full text Add to dashboard Cite

show abstract

“…A small optimisation of D eff, 50 from 337 -2.60 to -2.42 further reduced the root mean squared error to 0.038 (Figure 4). 338 suggested that the underlying mechanism of Cu toxicity is binding of Cu to thiol 373 groups in proteins and consequent damage to their structure (Letelier et al, 2005); this 374 has been noted as a reason for the sensitivity of plant ATPases to Cu (De Vos et al, 375 1991) and thus might also be related to the well-established effects of Cu on the 376 Na + /K + -ATPase in animals (e.g. Lauren and McDonald, 1986)).…”

Section: Application To the Chinese Dataset 325mentioning

confidence: 99%

Modelling the effects of copper on soil organisms and processes using the free ion approach: Towards a multi-species toxicity model

Lofts

Criel

Janssen

et al. 2013

Environmental Pollution

View full text Add to dashboard Cite

The free ion approach has been previously used to calculate critical limit 22 concentrations for soil metals based on point estimates of toxicity. Here, the approach 23 was applied to dose-response data for copper effects on seven biological endpoints in 24 each of 19 European soils. The approach was applied using the concept of an effective 25 dose, comprising a function of the concentrations of free copper and 'protective' 26 major cations, including H + . A significant influence of H + on the toxicity of Cu 2+ was 27 found, while the effects of other cations were inconsistent. The model could be 28 generalised by forcing the effect of H + and the slope of the dose-response relationship 29 to be equal for all endpoints. This suggests the possibility of a general bioavailability 30 model for copper effects on organisms. Furthermore, the possibility of such a model 31 could be explored for other cationic metals such as nickel, zinc, cadmium and lead. 32 33

show abstract

“…Copper participates in redox reactions that can generate reactive oxygen species (ROS), which damage lipids, proteins, and DNA. Copper can also directly bind to protein sulfhydryl and amino groups, leading to structural and functional modifications (13,30,38,41,68). Finally, copper can bind to DNA to form adducts and is involved in chromatin condensation (11,58).…”

mentioning

confidence: 99%

Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper

Song

Freedman

2009

Physiological Genomics

View full text Add to dashboard Cite

Copper is an essential trace element; however, at supraphysiological levels, it can be extremely toxic. Microarray data from HepG2 cells exposed to 100, 200, 400, and 600 μM copper for 4, 8, 12 and 24 h were generated and analyzed. Principal components, K-means, and hierarchical clustering, interactome, and pathway mapping analyses indicated that these exposure conditions induce physiological and toxicological changes in the HepG2 transcriptome. As a general trend, when the level of toxicity increases, the number and diversity of affected genes, Gene Ontology categories, regulatory pathways, and complexity of interactomes increase. Physiological responses to copper include transition metal ion binding and responses to stress/stimulus, whereas toxicological responses include apoptosis, morphogenesis, and negative regulation of biomolecule metabolism. The global gene expression profile was overlaid onto biomolecular interaction networks and signal transduction cascades using pathway mapping and interactome identification. This analysis indicated that copper modulates signal transduction pathways associated with MAPK, NF-κB, death receptor, IGF-I, hypoxia, IL-10, IL-2, IL-6, EGF, Toll-like receptor, protein ubiquitination, xenobiotic metabolism, leukocyte extravasation, complement and coagulation, and sonic hedgehog signaling. These results provide insights into the global and molecular mechanisms regulating the physiological and toxicological responses to metal exposure.

show abstract

Possible mechanisms underlying copper-induced damage in biological membranes leading to cellular toxicity

Cited by 213 publications

References 29 publications

Cu2+ and acute thermal stress induce protective eventsviathe p38-MAPK signalling pathway in the perfusedRana ridibundaheart

Cu2+ and acute thermal stress induce protective eventsviathe p38-MAPK signalling pathway in the perfusedRana ridibundaheart

Modelling the effects of copper on soil organisms and processes using the free ion approach: Towards a multi-species toxicity model

Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper

Contact Info

Product

Resources

About