Journal article
Deferasirox protects against hydrogen peroxide-induced cell apoptosis by inhibiting ubiquitination and degradation of p21WAF1/CIP1
Biochemical and biophysical research communications, Vol.524(3), pp.736-743
04/09/2020
DOI: 10.1016/j.bbrc.2020.01.155
Abstract
Deferasirox (DFX) is an iron chelator approved for the treatment of iron overload diseases. However, the role of DFX in oxidative stress-induced cell apoptosis and the exact molecular mechanisms underlying these processes remain poorly understood and require further investigation. In this study, we found that DFX rendered resistant to H2O2-induced apoptosis in HEK293T cells, reduced the intracellular levels of the labile iron pool (LIP) and oxidative stress induced by H2O2. Furthermore, DFX inhibited the ubiquitination and degradation of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21) via modulation of the interaction of p21 with SCF-Skp2. DFX also showed the inhibition effect on the activation of c-Jun N-terminal kinase (JNK), pro-caspase-3 and related mitochondrial apoptosis pathway induced by H2O2. These results provide novel insights into the molecular mechanism underpinning iron-mediated oxidative stress and apoptosis, and they may represent a promising target for therapeutic interventions in related pathological conditions.
•DFX suppresses H2O2-induced apoptosis.•DFX inhibits H2O2-induced upregulation of intracellular LIP and oxidative stress.•DFX decreases H2O2-induced ubiquitin-dependent degradation of p21.•DFX inhibits H2O2-induced the activation of JNK, pro-caspase-3, and related apoptosis pathway.
Details
- Title: Subtitle
- Deferasirox protects against hydrogen peroxide-induced cell apoptosis by inhibiting ubiquitination and degradation of p21WAF1/CIP1
- Creators
- Junhua Miao - Hebei Normal UniversityMutao Xu - Hebei Normal UniversityYuhuan Kuang - Hebei Normal UniversityShuhong Pan - Hebei Normal UniversityJianyuan Hou - Hebei Normal UniversityPengxiu Cao - Hebei Normal UniversityXianglin Duan - Hebei Normal UniversityYanzhong Chang - Hebei Normal UniversityHabelhah Hasem - University of IowaNan Zhou - Hebei Normal UniversityKe Tan - Hebei Normal UniversityYumei Fan - Hebei Normal University
- Resource Type
- Journal article
- Publication Details
- Biochemical and biophysical research communications, Vol.524(3), pp.736-743
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.bbrc.2020.01.155
- ISSN
- 0006-291X
- eISSN
- 1090-2104
- Grant note
- DOI: 10.13039/100010110, name: Hebei science and technology, award: ZD2016080; DOI: 10.13039/501100003481, name: Hebei Normal University, award: L2018Z07; DOI: 10.13039/501100001809, name: National Natural Science Foundation of China, award: 31701006; name: One Hundred Person Project of Hebei Province, award: E2016100019; DOI: 10.13039/501100003787, name: Natural Science Foundation of Hebei Province, award: C2017205129
- Language
- English
- Date published
- 04/09/2020
- Academic Unit
- Pathology
- Record Identifier
- 9984199919802771
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