Signaling pathway underlying the up-regulatory effect of TNF-alpha on the Na(+)/K(+) ATPase in HepG2 cells
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Updated: Jun 17, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Ari Kassardjian1, Zeina Dakroub, Ola El Zein
1Department of Biology, American University of Beirut, Lebanon.
Abstract:
The activity of the Na(+)/K(+) ATPase was shown to be reduced during apoptosis and enhanced during cell proliferation. This work investigated whether TNF-alpha exerts also opposite effects on the Na(+)/K(+) ATPase in HepG2 cells and whether these effects are time-dependent. A time response study demonstrated that the activity and protein expression of the ATPase are decreased at 1h and increased at 4, 6 and 8h. This work focused on the up-regulatory 4h-response. TNF-alpha was shown to exert a stimulatory effect on cJNK and NF-kappaB and an inhibitory effect on caspases which, in the basal state, down-regulate the ATPase. The cytokine was found to target the caspases by activating JNK which in turn activates NF-kappaB. The activated transcription factor inhibits the caspases and frees the ATPase from their inhibitory action leading thus to its up-regulation.
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