Please use this identifier to cite or link to this item:
https://doi.org/10.1016/j.taap.2008.03.025
DC Field | Value | |
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dc.title | Troglitazone-induced hepatic mitochondrial proteome expression dynamics in heterozygous Sod2+/- mice: Two-stage oxidative injury | |
dc.contributor.author | Lee, Y.H. | |
dc.contributor.author | Chung, M.C.M. | |
dc.contributor.author | Lin, Q. | |
dc.contributor.author | Boelsterli, U.A. | |
dc.date.accessioned | 2014-10-27T08:44:16Z | |
dc.date.available | 2014-10-27T08:44:16Z | |
dc.date.issued | 2008-08-15 | |
dc.identifier.citation | Lee, Y.H., Chung, M.C.M., Lin, Q., Boelsterli, U.A. (2008-08-15). Troglitazone-induced hepatic mitochondrial proteome expression dynamics in heterozygous Sod2+/- mice: Two-stage oxidative injury. Toxicology and Applied Pharmacology 231 (1) : 43-51. ScholarBank@NUS Repository. https://doi.org/10.1016/j.taap.2008.03.025 | |
dc.identifier.issn | 0041008X | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/102074 | |
dc.description.abstract | The determinants of susceptibility to troglitazone-induced idiosyncratic liver injury have not yet been determined; however, troglitazone has been shown to target mitochondria and induce mitochondria-mediated hepatocellular injury in vitro. The aim of this study was to use a systems approach to analyze the dynamics of mitochondrial changes at the proteome level and more clearly define the mechanisms and time course of troglitazone hepatotoxicity by using a previously characterized mouse model that is highly sensitized to troglitazone hepatotoxicity. Mice heterozygous in mitochondrial superoxide dismutase-2 (Sod2+/-) were injected intraperitoneally with troglitazone (30 mg/kg/day) or vehicle daily for 2 or 4 weeks. Hepatic mitochondria were isolated, purified, and subjected to two-dimensional difference gel electrophoresis (2D-DIGE). We found that among the ~ 1500 resolved hepatic mitochondrial proteins, 70 exhibited significantly altered abundance after troglitazone treatment. MALDI-TOF/TOF MS/MS analysis revealed that early changes (2 weeks) included increased levels of heat shock protein family members (mortalin, HSP7C), Lon protease, and catalase, indicating induction of a mitochondrial stress response. In contrast, after 4 weeks, a number of critical proteins including ATP synthase β-subunit, aconitase-2, and catalase exhibited decreased abundance, and total protein carbonyls were significantly increased, suggesting uncompensated oxidative damage. Aconitase-2 (ACO2) was decreased at both time points, making this protein a potential sensitive and early biomarker for mitochondrial oxidant stress. These results show that, in this murine model of underlying clinically silent mitochondrial stress, superimposed troglitazone induces a two-stage response: an initial adaptive response, followed by a toxic response involving oxidant injury to mitochondrial proteins. © 2008 Elsevier Inc. All rights reserved. | |
dc.description.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.taap.2008.03.025 | |
dc.source | Scopus | |
dc.subject | Drug-induced liver injury (DILI) | |
dc.subject | Idiosyncratic drug toxicity | |
dc.subject | Mitochondria | |
dc.subject | Oxidative stress | |
dc.subject | Proteomics | |
dc.subject | Superoxide dismutase | |
dc.subject | Troglitazone | |
dc.type | Article | |
dc.contributor.department | BIOLOGICAL SCIENCES | |
dc.description.doi | 10.1016/j.taap.2008.03.025 | |
dc.description.sourcetitle | Toxicology and Applied Pharmacology | |
dc.description.volume | 231 | |
dc.description.issue | 1 | |
dc.description.page | 43-51 | |
dc.description.coden | TXAPA | |
dc.identifier.isiut | 000258974400006 | |
Appears in Collections: | Staff Publications |
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