Actin cytoskeleton redox proteome oxidation by cadmium.
Epidemiological studies associate environmental cadmium (Cd) exposure with the risk of lung diseases. Although mechanisms are not fully elucidated, several studies demonstrate Cd effects on actin and actin-associated proteins. In a recent study of Cd at concentrations similar to environmental exposures, we found that redox-dependent inflammatory signaling by NF-κB was sensitive to the actin-disrupting agent, cytochalasin D. The goal of the present study was to use mass spectrometry-based redox proteomics to investigate Cd effects on the actin cytoskeleton proteome and related functional pathways in lung cells at low environmental concentrations. The results showed that Cd under conditions that did not alter total protein thiols or glutathione redox state caused significant oxidation of peptidyl Cys of proteins regulating actin cytoskeleton. Immunofluorescence microscopy of lung fibroblasts and pulmonary artery endothelial cells showed that low-dose Cd exposure stimulated filamentous actin formation and nuclear localization of destrin, an actin-depolymerizing factor. Taken together, the results show that redox states of peptidyl Cys in proteins associated with actin cytoskeleton pathways are selectively oxidized in lung by Cd at levels thought to occur from environmental exposure.
Emory Univ., 205 Whitehead Research Center, Atlanta, GA 30322. dpjones@emory.edu.
Young-Mi
YM
Go
Michael
M
Orr
Dean P
DP
Jones
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002478:Cells, Cultured; D003545:Cysteine / Q000378:metabolism; D051345:Destrin / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D021381:Protein Transport; D020543:Proteome / Q000378:metabolism*
D051345:Destrin; C495825:Dstn protein, mouse; D004785:Environmental Pollutants; D020543:Proteome; D002104:Cadmium; D008668:Metallothionein; D005978:Glutathione; D003545:Cysteine
cadmium; cysteine proteome; cytoskeleton remodeling; lung fibroblasts; pathway analysis