Format

Send to

Choose Destination
Chem Biol Interact. 2019 Feb 6. pii: S0009-2797(18)30618-5. doi: 10.1016/j.cbi.2019.02.001. [Epub ahead of print]

Daphnetin activates the Nrf2-dependent antioxidant response to prevent arsenic-induced oxidative insult in human lung epithelial cells.

Author information

1
Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, China.
2
Department of Traditional Chinese Medicine, The First Hospital of Jilin University, Changchun, China.
3
Department of Nephrology, The First Hospital of Jilin University, Changchun, China.
4
Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, China. Electronic address: lisa080205@163.com.

Abstract

NF-E2 p45-related factor 2 (Nrf2), which regulates the cellular antioxidant response, is a target for limiting tissue damage due to exposure to environmental toxicants, including arsenic. Daphnetin (Daph), a natural coumarin derivative, has been shown to induce remarkable antioxidant activity. The present study aimed to examine the protective effects and molecular mechanisms of Daph on arsenic-induced cytotoxicity in human lung epithelial cells. Our results demonstrate that Daph dramatically upregulated the antioxidant enzyme in a dose dependent manner, in association with induction of Nrf2 nuclear translocation and decreased Keap1 protein expression. Importantly, Daph also markedly induced the activation of AMP-activated protein kinase (AMPK), c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation. Furthermore, Daph antagonized the arsenic-induced decreases in cell viability and the generation of reactive oxygen species (ROS). Notably, Daph pretreatment reversed the arsenic-induced decrease in anti-apoptotic factor B-cell lymphoma-2 (Bcl-2) and the increase in pro-apoptotic factor Bcl-2-associated X protein (Bax). The effects of Daph on Nrf2 and HO-1 activation, and arsenic-induced cell viability were largely weakened when Nrf2 was depleted in vitro. Accordingly, Daph might ameliorate arsenic-induced cytotoxicity and apoptosis, which may be linked to the induction of Nrf2-dependent antioxidant responses as well as stabilization of the anti-apoptotic factor Bcl-2 in human lung epithelial cells.

KEYWORDS:

Arsenic; Daphnetin; Nrf2; Oxidative insult

PMID:
30738023
DOI:
10.1016/j.cbi.2019.02.001

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center