ReferenceID 3555
P66Shc mediated ferritin degradation--a novel mechanism of ROS formation
Free Radic Biol Med
Diallyl trisulfide (DATS) has been shown to induce the formation of reactive oxygen species (ROS) in prostate cancer cells, which was accompanied by a decrease in the ferritin protein level and an increase in the labile
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Record Fields
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- Reference Id
- 3555
- Evidence Id
- 20145
- Core Evidence Id
- 20145
- Source Reference Id
- 417
- Herb2 Reference Id
- HBREF000730
- Subject Paper Key
- HBIN015205_21616139
- Pubmed Id
- 21616139
- Doi
- 10.1016/j.freeradbiomed.2011.04.045
- Paper Title
- P66Shc mediated ferritin degradation--a novel mechanism of ROS formation
- Paper Abstract
- Diallyl trisulfide (DATS) has been shown to induce the formation of reactive oxygen species (ROS) in prostate cancer cells, which was accompanied by a decrease in the ferritin protein level and an increase in the labile iron pool (LIP). However, the mechanism of the ferritin degradation has not been fully elucidated. In this paper we demonstrate that DATS-induced ROS formation depends on p66Shc. In cells stably expressing a dominant negative mutant of p66Shc (p66ShcS36A), DATS did not induce ROS formation. In addition, in cells expressing p66ShcS36A neither an increase in ferritin H degradation nor an increase in LIP were observed. Cells stably expressing p66ShcS36A also possess higher levels of ferritin H compared to PC-3 cells transfected with an empty vector. Moreover, DATS-induced G2/M arrest is completely abrogated in cells expressing p66ShcS36A. Mouse embryonic fibroblasts (MEFs) derived from wild-type (WT) or p66Shc knockout mouse have been used to evaluate if p66Shc involvement in DATS-induced signaling is cell specific. DATS induced G2/M arrest in WT MEFs but had no effect in the p66Shc(-/-) cell line. Moreover, increases in LIP and ROS formation were significantly attenuated in p66Shc(-/-) MEFs treated with DATS.
- Journal
- Free Radic Biol Med
- Publish Year
- 2011
- Experiment Subject
- Experiment Type
- Cell Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- P66Shc mediated ferritin degradation--a novel mechanism of ROS formation
- Bilingual Status
- semi_complete