n/a
Abstract Title:

Tanshinone IIA pretreatment promotes cell survival in human lung epithelial cells under hypoxia via AP-1-Nrf2 transcription factor.

Abstract Source:

Cell Stress Chaperones. 2020 Mar 6. Epub 2020 Mar 6. PMID: 32144684

Abstract Author(s):

Seema Yadav, Mrinalini Singh, Som Nath Singh, Bhuvnesh Kumar

Article Affiliation:

Seema Yadav

Abstract:

Activator protein-1 (AP-1) plays a decisive role in cell proliferation, apoptosis, and inflammation under hypoxia; thus, AP-1 subunits or dimers could be modulated for a desired phenomenon in a cell using a suitable compound of therapeutic potential. Herein, we used Tanshinone-IIA as an AP-1 (subunits) modulator, and the purpose of the study was to investigate the signaling mechanism exhibited by Tan-IIA in facilitating tolerance to hypoxia. A549 cells were pretreated with Tan-IIA and exposed to hypoxia for 6, 12, 24, and 48 h. Biochemical and molecular parameters were assessed in order to trace the signaling pathway. Tan-IIA attenuated hypoxia-induced oxidative stress by modulating the expression of AP-1 subunits (via. MAPK) and Nrf2 transcription factor, which in turn were responsible for maintaining the higher levels of antioxidant enzymes and genes (HO). Tan-IIA increased the cell survival. This could be attributed to an increased NO level via iNOS gene and activated JNK, ERK pathway that induced c-jun/c-fos, c-jun/fosB, junD/c-fos, and junD/fosB heterodimers. This in turn leads to the cell cycle progressionby activating cyclins (D and B). This was further confirmed by the lower levels of p53 and their downstream genes (p16, p21, p27). In addition, Tan-IIA decreased pro-inflammatory cytokine levels by inhibiting the formation of junB/fra-1 heterodimer regulated by p38. Tan-IIA increased cell survivalto hypoxia by maintaining the higher levels of cellular iNOS, HO-1, jun-D, c-jun, fos B via Nrf2-AP-1.

Study Type : In Vitro Study

Print Options


Key Research Topics

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2024 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.