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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

Molecules and Cells 2020년 43권 9호 p.813 ~ 820
문영철, 안지영, 유은선, 이경은, 남은미, 허정원, Woo Hyun-Ae, Rhee Sue-Goo, 성주명,
소속 상세정보
문영철 ( Mun Yeung-Chul ) - Ewha Womans University College of Medicine Department of Internal Medicine
안지영 ( Ahn Jee-Young ) - Ewha Womans University College of Medicine Department of Internal Medicine
유은선 ( Yoo Eun-Sun ) - Ewha Womans University College of Medicine Department of Pediatrics
이경은 ( Lee Kyoung-Eun ) - Ewha Womans University College of Medicine Department of Internal Medicine
남은미 ( Nam Eun-Mi ) - Ewha Womans University College of Medicine Department of Internal Medicine
허정원 ( Huh Jung-Won ) - Ewha Womans University College of Medicine Department of Laboratory Medicine
 ( Woo Hyun-Ae ) - Ewha Womans University Graduate School of Pharmaceutical Sciences
 ( Rhee Sue-Goo ) - Yonsei University College of Medicine Yonsei Biomedical Research Institute
성주명 ( Seong Chu-Myong ) - Ewha Womans University College of Medicine Department of Internal Medicine

Abstract


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 MitoSOXTM Red mitochondrial superoxide indicator were used to detect intracellular and mitochondrial reactive oxygen species (ROS). The steady-state level of SO2 (Cysteine sulfinic acid, Cys?SO2H) 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 SO2 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.

키워드

acute promyelocytic leukemia; arsenic trioxide; peroxiredoxin 3

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