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Peroxiredoxin 3 Has Important Roles on Arsenic Trioxide Induced Apoptosis in Human Acute Promyelocytic Leukemia Cell Line via Hyperoxidation of Mitochondrial Specific Reactive Oxygen Species

NB4 cell, the human acute promyelocytic leukemia (APL) cell line, was treated with various concentrations of arsenic trioxide (ATO) to induce apoptosis, measured by staining with 7-amino-actinomycin D (7-AAD) by flow cytometry. 2’, 7’-dichlorodihydro-fluorescein-diacetate (DCF-DA) and MitoSOX(TM) Re...

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Autores principales: Mun, Yeung-Chul, Ahn, Jee Young, Yoo, Eun Sun, Lee, Kyoung Eun, Nam, Eun Mi, Huh, Jungwon, Woo, Hyun Ae, Rhee, Sue Goo, Seong, Chu Myong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Molecular and Cellular Biology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528683/
https://www.ncbi.nlm.nih.gov/pubmed/32975211
http://dx.doi.org/10.14348/molcells.2020.2234
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author Mun, Yeung-Chul
Ahn, Jee Young
Yoo, Eun Sun
Lee, Kyoung Eun
Nam, Eun Mi
Huh, Jungwon
Woo, Hyun Ae
Rhee, Sue Goo
Seong, Chu Myong
author_facet Mun, Yeung-Chul
Ahn, Jee Young
Yoo, Eun Sun
Lee, Kyoung Eun
Nam, Eun Mi
Huh, Jungwon
Woo, Hyun Ae
Rhee, Sue Goo
Seong, Chu Myong
author_sort Mun, Yeung-Chul
collection PubMed
description NB4 cell, the human acute promyelocytic leukemia (APL) cell line, was treated with various concentrations of arsenic trioxide (ATO) to induce apoptosis, measured by staining with 7-amino-actinomycin D (7-AAD) by flow cytometry. 2’, 7’-dichlorodihydro-fluorescein-diacetate (DCF-DA) and MitoSOX(TM) Red mitochondrial superoxide indicator were used to detect intracellular and mitochondrial reactive oxygen species (ROS). The steady-state level of SO(2) (Cysteine sulfinic acid, Cys-SO(2)H) form for peroxiredoxin 3 (PRX3) was measured by a western blot. To evaluate the effect of sulfiredoxin 1 depletion, NB4 cells were transfected with small interfering RNA and analyzed for their influence on ROS, redox enzymes, and apoptosis. The mitochondrial ROS of NB4 cells significantly increased after ATO treatment. NB4 cell apoptosis after ATO treatment increased in a time- dependent manner. Increased SO(2) form and dimeric PRX3 were observed as a hyperoxidation reaction in NB4 cells post- ATO treatment, in concordance with mitochondrial ROS accumulation. Sulfiredoxin 1 expression is downregulated by small interfering RNA transfection, which potentiated mitochondrial ROS generation and cell growth arrest in ATO- treated NB4 cells. Our results indicate that ATO-induced ROS generation in APL cell mitochondria is attributable to PRX3 hyperoxidation as well as dimerized PRX3 accumulation, subsequently triggering apoptosis. The downregulation of sulfiredoxin 1 could amplify apoptosis in ATO-treated APL cells.
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spelling pubmed-75286832020-10-08 Peroxiredoxin 3 Has Important Roles on Arsenic Trioxide Induced Apoptosis in Human Acute Promyelocytic Leukemia Cell Line via Hyperoxidation of Mitochondrial Specific Reactive Oxygen Species Mun, Yeung-Chul Ahn, Jee Young Yoo, Eun Sun Lee, Kyoung Eun Nam, Eun Mi Huh, Jungwon Woo, Hyun Ae Rhee, Sue Goo Seong, Chu Myong Mol Cells Research Article NB4 cell, the human acute promyelocytic leukemia (APL) cell line, was treated with various concentrations of arsenic trioxide (ATO) to induce apoptosis, measured by staining with 7-amino-actinomycin D (7-AAD) by flow cytometry. 2’, 7’-dichlorodihydro-fluorescein-diacetate (DCF-DA) and MitoSOX(TM) Red mitochondrial superoxide indicator were used to detect intracellular and mitochondrial reactive oxygen species (ROS). The steady-state level of SO(2) (Cysteine sulfinic acid, Cys-SO(2)H) form for peroxiredoxin 3 (PRX3) was measured by a western blot. To evaluate the effect of sulfiredoxin 1 depletion, NB4 cells were transfected with small interfering RNA and analyzed for their influence on ROS, redox enzymes, and apoptosis. The mitochondrial ROS of NB4 cells significantly increased after ATO treatment. NB4 cell apoptosis after ATO treatment increased in a time- dependent manner. Increased SO(2) form and dimeric PRX3 were observed as a hyperoxidation reaction in NB4 cells post- ATO treatment, in concordance with mitochondrial ROS accumulation. Sulfiredoxin 1 expression is downregulated by small interfering RNA transfection, which potentiated mitochondrial ROS generation and cell growth arrest in ATO- treated NB4 cells. Our results indicate that ATO-induced ROS generation in APL cell mitochondria is attributable to PRX3 hyperoxidation as well as dimerized PRX3 accumulation, subsequently triggering apoptosis. The downregulation of sulfiredoxin 1 could amplify apoptosis in ATO-treated APL cells. Korean Society for Molecular and Cellular Biology 2020-09-30 2020-09-22 /pmc/articles/PMC7528683/ /pubmed/32975211 http://dx.doi.org/10.14348/molcells.2020.2234 Text en © The Korean Society for Molecular and Cellular Biology. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Research Article
Mun, Yeung-Chul
Ahn, Jee Young
Yoo, Eun Sun
Lee, Kyoung Eun
Nam, Eun Mi
Huh, Jungwon
Woo, Hyun Ae
Rhee, Sue Goo
Seong, Chu Myong
Peroxiredoxin 3 Has Important Roles on Arsenic Trioxide Induced Apoptosis in Human Acute Promyelocytic Leukemia Cell Line via Hyperoxidation of Mitochondrial Specific Reactive Oxygen Species
title Peroxiredoxin 3 Has Important Roles on Arsenic Trioxide Induced Apoptosis in Human Acute Promyelocytic Leukemia Cell Line via Hyperoxidation of Mitochondrial Specific Reactive Oxygen Species
title_full Peroxiredoxin 3 Has Important Roles on Arsenic Trioxide Induced Apoptosis in Human Acute Promyelocytic Leukemia Cell Line via Hyperoxidation of Mitochondrial Specific Reactive Oxygen Species
title_fullStr Peroxiredoxin 3 Has Important Roles on Arsenic Trioxide Induced Apoptosis in Human Acute Promyelocytic Leukemia Cell Line via Hyperoxidation of Mitochondrial Specific Reactive Oxygen Species
title_full_unstemmed Peroxiredoxin 3 Has Important Roles on Arsenic Trioxide Induced Apoptosis in Human Acute Promyelocytic Leukemia Cell Line via Hyperoxidation of Mitochondrial Specific Reactive Oxygen Species
title_short Peroxiredoxin 3 Has Important Roles on Arsenic Trioxide Induced Apoptosis in Human Acute Promyelocytic Leukemia Cell Line via Hyperoxidation of Mitochondrial Specific Reactive Oxygen Species
title_sort peroxiredoxin 3 has important roles on arsenic trioxide induced apoptosis in human acute promyelocytic leukemia cell line via hyperoxidation of mitochondrial specific reactive oxygen species
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528683/
https://www.ncbi.nlm.nih.gov/pubmed/32975211
http://dx.doi.org/10.14348/molcells.2020.2234
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