Premium
Alleviation of cadmium‐induced oxidative stress by trehalose via inhibiting the Nrf2‐Keap1 signaling pathway in primary rat proximal tubular cells
Author(s) -
Wang XinYu,
Wang ZhenYong,
Zhu YiSong,
Zhu SiMing,
Fan RuiFeng,
Wang Lin
Publication year - 2018
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22011
Subject(s) - keap1 , oxidative stress , chemistry , superoxide dismutase , gclm , glutathione , heme oxygenase , biochemistry , glutathione reductase , nad+ kinase , reactive oxygen species , ubiquitin ligase , antioxidant , microbiology and biotechnology , gclc , glutathione peroxidase , transcription factor , heme , biology , enzyme , ubiquitin , gene
Nuclear factor erythroid 2‐related factor 2 (Nrf2) is a transcription factor that regulates a cluster of oxidative stress‐inducible genes in cells. Here, we aimed to investigate whether trehalose (Tre) protects primary rat proximal tubular (rPT) cells against cadmium (Cd)‐induced oxidative stress via Nrf2 antioxidant pathway. Data showed that Tre treatment inhibited Nrf2 nuclear translocation and restored the decline in Kelch‐like ECH‐associated protein 1 (Keap1) protein level in Cd‐exposed rPT cells. Moreover, Cd‐activated Nrf2 target genes, including phase II detoxifying enzymes, that is, NAD(P)H quinone oxidoreductase 1 and heme oxygenase‐1, direct antioxidant proteins, that is, glutathione peroxidase, superoxide dismutase, catalase, and glutathione biosynthesis‐related proteins, that is, glutamatecysteine ligase catalytic subunit, glutamate cysteine ligase modifier subunit, and glutathione reductase, were all downregulated by co‐treatment with Tre. Collectively, these findings demonstrate that Tre treatment alleviates Cd‐induced oxidative stress in rPT cells by inhibiting the Nrf2‐Keap1 signaling pathway.