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

Cell Stress & Chaperones
Seema YadavBhuvnesh Kumar

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 progression by activating cyclins (D and B). This was further confirmed by the lower levels of p53 and their downstream genes (p1...Continue Reading

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Citations

Jan 20, 2021·Expert Review of Clinical Pharmacology·Jun FengJunshuai Wang
Nov 13, 2021·Frontiers in Genetics·Bei WuChen Wang

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Methods Mentioned

BETA
ELISA
FACS
Assay
X-ray
flow cytometry
environmental stress

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