Cadmium-induced glutathionylation of actin occurs through a ROS-independent mechanism: Implications for cytoskeletal integrity

Choong, Grace; Liu, Ying; Wu, Xiao; Templeton, Douglas M.

doi:10.1016/j.taap.2013.07.002

Cited by 20 publications

(15 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cadmium toxicity is known to be dependent on protein denaturation and oxidative stress (Stohs, 1995;Stohs & Bagchi, 1995;Suzuki et al, 2001). Moreover cadmium has been shown to interfere with the integrity of the actin cytoskeleton and the function of the cadherin cell-cell adhesion molecules (Prozialeck & Edwards, 2012;Choong et al, 2013a). Cadmium exposure has also been shown to disrupt vinculin-and focal adhesion kinase-rich focal contacts through a Ca 2+ /calmodulin-dependent protein kinase II (CaMK-II) pathway cell (Choong et al, 2013b).…”

Section: Discussionmentioning

confidence: 99%

European sea bass gill pathology after exposure to cadmium and terbuthylazine: expert versus fractal analysis

Manera

Giari

DePasquale

et al. 2015

Journal of Microscopy

View full text Add to dashboard Cite

The objective of this study was to compare expert versus fractal analysis as new methods to evaluate branchial lamellar pathology in European sea bass Dicentrarchus labrax (Linnaeus, 1758) experimentally exposed to cadmium and to terbuthylazine. In particular, guided expert quantitative and fractal analysis were performed on selected images from semithin sections to test possible differences according to exposure class (unexposed, cadmium exposed, or terbuthylazine exposed) and the discrimination power of the two methods. With respect to guided expert quantitative analysis, the following elementary pathological features were assessed according to pre-determined cover classes: 'epithelial lifting', 'epithelial shrinkage', 'epithelial swelling', 'pillar cells coarctation', 'pillar cells detachment', 'channels fusion', 'chloride cells swelling' and 'chloride cells invasion'. Considering fractal analysis, DB (box dimension), DM (mass dimension), Dx (mean fractal dimension) as fractal dimensions and lacunarity from DM and Dx scan types were calculated both from the outlined and skeletonized (one pixel wide lines) images. Despite significant differences among experimental classes, only expert analysis provided good discrimination with correct classification of 91.7 % of the original cases, and of 87.5 % of the cross-validated cases, with a sensitivity of 95.45 % and 91.3 %, respectively, and a specificity of 75 % in both cases. Guided expert quantitative analysis appears to be a reliable method to objectively characterize fish gill pathology and may represent a powerful tool in environmental biomonitoring to ensure proper standardization and reproducibility. Though fractal analysis did not equal the discrimination power of the expert method, it certainly warrants further study to evaluate local variations in complexity or possible multiple scaling rules.

show abstract

Section: Discussionmentioning

confidence: 99%

European sea bass gill pathology after exposure to cadmium and terbuthylazine: expert versus fractal analysis

Manera

Giari

DePasquale

et al. 2015

Journal of Microscopy

View full text Add to dashboard Cite

show abstract

“…1B). The generation of ROS triggers actin cytoskeleton reorganization [21,22]. Thus we tested the effect of SalA on intracellular ROS level.…”

Section: Discussionmentioning

confidence: 99%

SalA Attenuates Ischemia/Reperfusion-Induced Endothelial Barrier Dysfunction via Down-Regulation of VLDL Receptor Expression

Yang

Zhang

Wang³

et al. 2014

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Salvianolic acid A (SalA) has been shown to confer robust protection against endothelial injury. VLDL receptor is expressed at high levels on the endothelial surface, however its biological effect on endothelial cells has not yet been completely elucidated. Here, we investigated molecular effects of SalA on endothelial VLDL expression and barrier dysfunction under conditions of ischemia/reperfusion (IS/RP). Methods: Human umbilical vein endothelial cells (HUVECs) treated with SalA were subjected to IS/RP stimulation. Endothelial permeability, ZO-1 distribution, actin cytoskeleton reorganization, and intracellular reactive oxygen species (ROS) generation were examined. The mRNA levels were tested by real-time RT-PCR and the protein levels were determined by immunoblot analysis. Results: Pretreatment of HUVECs with SalA markedly attenuated IS/RP-induced endothelial hyperpermeability, discontinuous ZO-1 staining, actin stress fiber formation, and intracellular ROS generation. IS/RP activated p38 MAPK signaling and enhanced VLDL receptor expression, and inactivation of p38 MAPK abolished increase of VLDL receptor expression. Furthermore, siRNA experiments showed that VLDL receptor was a crucial mediator of endothelial barrier dysfunction and intracellular ROS generation induced by IS/RP. Importantly, SalA effectively suppressed IS/RP-induced activation of p38 MAPK signaling and increase of VLDL receptor expression. Conclusion: These results for the first time demonstrated that SalA protected against IS/RP-induced endothelial barrier dysfunction through suppression of VLDL receptor expression.

show abstract

“…Ethidium bromide-stained gels were scanned and quantified using Image J. 2.6.5 Total and reduced glutathione: Glutathione (GSH) was measured using a 5,5′dithio-bis-(2-nitrobenzoic acid) (DTNB) recycling assay as described [14]. Briefly, equal amounts of cell lysate were deproteinized using Deproteinizing Sample Preparation Kit (Biovision; San Francisco, CA.).…”

Section: Cell Fractionationmentioning

confidence: 99%

Iron-dependent turnover of IRP-1/c-aconitase in kidney cells

Liu

Templeton

2015

Metallomics

Self Cite

View full text Add to dashboard Cite

The kidney plays an important role in iron homeostasis and actively reabsorbs citrate. The bifunctional iron-regulatory protein IRP-1 potentially regulates iron trafficking and participates in citrate metabolism as a cytosolic (c-) aconitase. We investigated the role of cellular iron status in determining the expression and dynamics of IRP-1 in two renal cell types, with the aim of identifying a role of the protein in cellular ROS levels, citrate metabolism and glutamate production. The effects of iron supplementation and chelation on IRP-1 protein and mRNA levels and protein turnover were compared in cultured primary rat mesangial cells and a porcine renal tubule cell line (LLC-PK1). Levels of ROS were measured in both cell types, and c-aconitase activity, glutamate, and glutathione were measured in LLC-PK1 cells, with and without IRP-1 silencing and in glutamine-supplemented or nominally glutamine-free medium. Iron supplementation decreased IRP-1 levels (e.g., approx. 40% in mesangial cells treated with 10 μg ml(-1) iron for 16 h) and increased ubiquitinated IRP-1 levels in both cells types, with iron chelation having the opposite effect. Although iron increased ROS levels (three-fold with 20 μg ml(-1) iron in mesangial cells and more modestly by about 30% with 50 μg ml(-1) in LLC-PK1 cells, both after 24 h), protein degradation was not ROS-dependent. In LLC-PK1 cells, 10 μg ml(-1) iron (24 h) increased both aconitase activity (30%) and secreted glutamate levels (65%). Silencing did not remove the glutamate response to iron but decreased the c-aconitase activity of the residual protein independent of iron loading (37% and 46% of control levels, without and with iron treatment, respectively). However, in glutamine-free medium, glutamate was still increased by iron, even in IRP-1-silenced cells, and did not correspond to c-aconitase. Silencing decreased the amount of ferritin measured in response to iron loading, decreased the affect of iron on total glutathione by 48%, and increased the response of ROS to iron loading by 38%. We conclude that iron increases turnover of IRP-1 in kidney cells, while increasing aconitase activity, suggesting that the apoprotein (aconitase-inactive) form is not exclusively responsible for turnover. Iron increases glutamate levels in tubule epithelial cells, but this appears to be independent of c-aconitase activity or the availability of extracellular glutamine. IRP-1 protein levels are not regulated by ROS, but IRP-1-dependent ferritin expression may decrease ROS and increase total glutathione levels, suggesting that ferritin levels are more important than citrate metabolism in protecting renal cells against iron.

show abstract

Cadmium-induced glutathionylation of actin occurs through a ROS-independent mechanism: Implications for cytoskeletal integrity

Cited by 20 publications

References 32 publications

European sea bass gill pathology after exposure to cadmium and terbuthylazine: expert versus fractal analysis

European sea bass gill pathology after exposure to cadmium and terbuthylazine: expert versus fractal analysis

SalA Attenuates Ischemia/Reperfusion-Induced Endothelial Barrier Dysfunction via Down-Regulation of VLDL Receptor Expression

Iron-dependent turnover of IRP-1/c-aconitase in kidney cells

Contact Info

Product

Resources

About