In vitro study on effect of bardoxolone methyl on cisplatin-induced cellular senescence in human proximal tubular cells.
Acute Kidney injury
Apoptosis
CDDO-Me
Cellular senescence
Nrf2
Journal
Molecular and cellular biochemistry
ISSN: 1573-4919
Titre abrégé: Mol Cell Biochem
Pays: Netherlands
ID NLM: 0364456
Informations de publication
Date de publication:
Mar 2022
Mar 2022
Historique:
received:
09
06
2021
accepted:
04
11
2021
pubmed:
2
1
2022
medline:
26
3
2022
entrez:
1
1
2022
Statut:
ppublish
Résumé
Bardoxolone methyl [methyl-2-cyano-3, 12-dioxooleana-1, 9(11)dien-28-oate (CDDO-Me)], an activator of the nuclear factor erythroid-derived 2-related factor2 pathway, is a potential therapeutic candidate for the treatment of kidney diseases. However, its effect against cellular senescence remains unclear. This study aimed to investigate whether CDDO-Me protects cells against cisplatin-induced cellular senescence using an in vitro model. The human renal proximal tubular epithelial cell line HK-2 was treated with cisplatin for 6 h, followed by treatment with or without CDDO-Me (0.1 or 0.2 μmol/L). Senescence markers were analyzed using western blotting and real-time PCR. Apoptosis was evaluated through TUNEL staining. Cisplatin induced changes in the levels of markers specific for proliferation, cell cycle, and senescence in a time- and dose-dependent manner. Furthermore, IL-6 and IL-8 levels in the culture medium increased markedly. These data suggested that cellular senescence-like alterations occurred in HK-2 cells exposed to cisplatin. CDDO-Me treatment reversed the cisplatin-mediated alterations in the levels of cellular senescence markers. The antioxidant enzymes, HO1, NQO1, GPX1, and CAT were upregulated by CDDO-Me treatment. Furthermore, CDDO-Me treatment induced apoptosis in cisplatin-exposed HK-2 cells. Pretreatment with Ac-DEVD-CHO, the caspase inhibitor, suppressed the reversal effect of CDDO-Me against cisplatin-induced cellular senescence-like alterations. This study showed that CDDO-Me attenuated cisplatin-induced premature senescence of HK-2 cells. This beneficial effect may be related to Nrf2 activation. Our findings also showed that CDDO-Me induced apoptosis in cisplatin-treated HK-2 cells, potentially protecting the kidneys from cellular senescence. CDDO-Me appears to be a candidate treatment for acute kidney injury.
Identifiants
pubmed: 34973124
doi: 10.1007/s11010-021-04295-y
pii: 10.1007/s11010-021-04295-y
pmc: PMC8857011
doi:
Substances chimiques
Oleanolic Acid
6SMK8R7TGJ
bardoxolone methyl
CEG1Q6OGU1
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
689-699Subventions
Organisme : Kitasato University School of Allied Health Sciences
ID : Grant-in-Aid for Research Project
Organisme : Kitasato University School of Allied Health Sciences
ID : 2021-1022
Organisme : Kitasato University School of Allied Health Sciences
ID : 2019-1053
Organisme : Kitasato University School of Allied Health Sciences
ID : 2020-1047
Organisme : JSPS KAKENHI
ID : Grant-in-Aid for Scientific Research (C) No. JP19K07944
Organisme : Kitasato University
ID : Research Grant for Young Researchers 2019-19
Informations de copyright
© 2021. The Author(s).
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