Prooxidant Properties of p66shc Are Mediated by Mitochondria in Human Cells
p66shc is a protein product of an mRNA isoform of SHC1 gene that has a pro-oxidant and pro-apoptotic activity and is implicated in the aging process. Mitochondria were suggested as a major source of the p66shc-mediated production of reactive oxygen species (ROS), although the underlying mechanisms a...
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Public Library of Science
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950296/ |
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pubmed-39502962014-03-12 Prooxidant Properties of p66shc Are Mediated by Mitochondria in Human Cells Galimov, Evgeny R. Chernyak, Boris V. Sidorenko, Alena S. Tereshkova, Alesya V. Chumakov, Peter M. Research Article p66shc is a protein product of an mRNA isoform of SHC1 gene that has a pro-oxidant and pro-apoptotic activity and is implicated in the aging process. Mitochondria were suggested as a major source of the p66shc-mediated production of reactive oxygen species (ROS), although the underlying mechanisms are poorly understood. We studied effects of p66shc on oxidative stress induced by hydrogen peroxide or by serum deprivation in human colon carcinoma cell line RKO and in diploid human dermal fibroblasts (HDFs). An shRNA-mediated knockdown of p66shc suppressed and an overexpression of a recombinant p66shc stimulated the production of ROS in the both models. This effect was not detected in the mitochondrial DNA-depleted ρ0-RKO cells that do not have the mitochondrial electron transport chain (ETC). The p66shc-dependent accumulation of mitochondrial ROS was detected with HyPer-mito, a mitochondria-targeted fluorescent protein sensor for hydrogen peroxide. The fragmentation of mitochondria induced by mitochondrial ROS was significantly reduced in the p66shc deficient RKO cells. Mitochondria-targeted antioxidants SkQ1 and SkQR1 also decreased the oxidative stress induced by hydrogen peroxide or by serum deprivation. Together the data indicate that the p66shc-dependant ROS production during oxidative stress has mitochondrial origin in human normal and cancer cells. Public Library of Science 2014-03-11 /pmc/articles/PMC3950296/ /pubmed/24618848 http://dx.doi.org/10.1371/journal.pone.0086521 Text en © 2014 Galimov et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Galimov, Evgeny R. Chernyak, Boris V. Sidorenko, Alena S. Tereshkova, Alesya V. Chumakov, Peter M. |
| spellingShingle |
Galimov, Evgeny R. Chernyak, Boris V. Sidorenko, Alena S. Tereshkova, Alesya V. Chumakov, Peter M. Prooxidant Properties of p66shc Are Mediated by Mitochondria in Human Cells |
| author_facet |
Galimov, Evgeny R. Chernyak, Boris V. Sidorenko, Alena S. Tereshkova, Alesya V. Chumakov, Peter M. |
| author_sort |
Galimov, Evgeny R. |
| title |
Prooxidant Properties of p66shc Are Mediated by Mitochondria in Human Cells |
| title_short |
Prooxidant Properties of p66shc Are Mediated by Mitochondria in Human Cells |
| title_full |
Prooxidant Properties of p66shc Are Mediated by Mitochondria in Human Cells |
| title_fullStr |
Prooxidant Properties of p66shc Are Mediated by Mitochondria in Human Cells |
| title_full_unstemmed |
Prooxidant Properties of p66shc Are Mediated by Mitochondria in Human Cells |
| title_sort |
prooxidant properties of p66shc are mediated by mitochondria in human cells |
| description |
p66shc is a protein product of an mRNA isoform of SHC1 gene that has a pro-oxidant and pro-apoptotic activity and is implicated in the aging process. Mitochondria were suggested as a major source of the p66shc-mediated production of reactive oxygen species (ROS), although the underlying mechanisms are poorly understood. We studied effects of p66shc on oxidative stress induced by hydrogen peroxide or by serum deprivation in human colon carcinoma cell line RKO and in diploid human dermal fibroblasts (HDFs). An shRNA-mediated knockdown of p66shc suppressed and an overexpression of a recombinant p66shc stimulated the production of ROS in the both models. This effect was not detected in the mitochondrial DNA-depleted ρ0-RKO cells that do not have the mitochondrial electron transport chain (ETC). The p66shc-dependent accumulation of mitochondrial ROS was detected with HyPer-mito, a mitochondria-targeted fluorescent protein sensor for hydrogen peroxide. The fragmentation of mitochondria induced by mitochondrial ROS was significantly reduced in the p66shc deficient RKO cells. Mitochondria-targeted antioxidants SkQ1 and SkQR1 also decreased the oxidative stress induced by hydrogen peroxide or by serum deprivation. Together the data indicate that the p66shc-dependant ROS production during oxidative stress has mitochondrial origin in human normal and cancer cells. |
| publisher |
Public Library of Science |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3950296/ |
| _version_ |
1612066535767015424 |