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Cheng, W.Y.* ; Tong, H.Y.* ; Miller, E.W.* ; Chang, C.J.* ; Remington, J.* ; Zucker, R.M.* ; Bromberg, P.A.* ; Samet, J.M.* ; Hofer, T.P.

An integrated imaging approach to the study of oxidative stress generation by mitochondrial dysfunction in living cells.

Environ. Health Perspect. 118, 902-908 (2010)
Verlagsversion Volltext DOI PMC
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BACKGROUND: The mechanisms of action of many environmental agents commonly involve oxidative stress resulting from mitochondrial dysfunction. Zinc is a common environmental metallic contaminant that has been implicated in a variety of oxidant-dependent toxicological responses. Unlike ions of other transition metals such as iron, copper, and vanadium, Zn(2+) does not generate reactive oxygen species (ROS) through redox cycling. OBJECTIVE: To characterize the role of oxidative stress in zinc-induced toxicity. METHODS: We used an integrated imaging approach that employs the hydrogen peroxide (H2O2)-specific fluorophore Peroxy Green 1 (PG1), the mitochondrial potential sensor 5,5 ,6,6 -tetrachloro-1,1 ,3,3 -tetraethylbenzimidazolylcarbocyanine iodide (JC-1), and the mitochondria-targeted form of the redox-sensitive genetically encoded fluorophore MTroGFP1 in living cells. RESULTS: Zinc treatment in the presence of the Zn(2+) ionophore pyrithione of A431 skin carcinoma cells preloaded with the H(2)O(2)-specific indicator PG1 resulted in a significant increase in H(2)O(2) production that could be significantly inhibited with the mitochondrial inhibitor carbonyl cyanide 3-chlorophenylhydrazone. Mitochondria were further implicated as the source of zinc-induced H(2)O(2) formation by the observation that exposure to zinc caused a loss of mitochondrial membrane potential. Using MTroGFP1, we showed that zinc exposure of A431 cells induces a rapid loss of reducing redox potential in mitochondria. We also demonstrated that zinc exposure results in rapid swelling of mitochondria isolated from mouse hearts. CONCLUSION: Taken together, these findings show a disruption of mitochondrial integrity, H(2)O(2) formation, and a shift toward positive redox potential in cells exposed to zinc. These data demonstrate the utility of real-time, live-cell imaging to study the role of oxidative stress in toxicological responses.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Biosensors; Confocal microscopy; Hydrogen peroxide; Mitochondrial dysfunction; Oxidative stress; Real-time imaging; ROS; GREEN FLUORESCENT PROTEIN; AIRWAY EPITHELIAL-CELLS; SLIDE-BASED SYSTEMS; QUALITY ASSESSMENT; INDICATORS; ZINC; RECEPTOR; COMPLEX; METABOLISM; INHIBITION
ISSN (print) / ISBN 0091-6765
e-ISSN 1552-9924
Zeitschrift Environmental Health Perspectives
Quellenangaben Band: 118, Heft: 7, Seiten: 902-908 Artikelnummer: , Supplement: ,
Verlag Research Triangle Park
Verlagsort NC [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)