JNK modulates the effect of caspases and NF-κB in the TNF-α-induced down-regulation of Na+/K+ATPase in HepG2 cells

✍ Scribed by Ari Kassardjian; Sawsan Ibrahim Kreydiyyeh

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 279 KB
• Volume: 216
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.21436

✦ Synopsis

Abstract

An inhibition of the Na^+^/K^+^ATPase was previously shown to accompany and potentiate apoptosis in different experimental models. Since TNF‐α is known to be a pro and anti‐apoptotic cytokine, this work was undertaken to study the effect of TNF‐α on the Na^+^/K^+^ATPase in HepG2 cells and to determine the signaling pathway involved. Cells were incubated for 1 h with TNF‐α in presence and absence of PDTC, SP600125 and FK009, respective inhibitors of NF‐KB, c‐JNK, and caspases. The activity of the pump was assayed by measuring the ouabain‐inhibitable release of inorganic phosphate, and changes in its expression were monitored by western blot analysis. TNF‐α decreased significantly the activity and protein expression of the Na^+^/K^+^ATPase. NF‐κB and caspases were found to be the main effectors of the cytokine, mediating respectively down‐regulation and up‐regulation of the pump. Their activity was however modulated at 1 h by c‐JNK, which stimulated the caspases and inhibited NF‐κB, resulting in a net inhibition of the ATPase, and probably favoring the apoptotic pathway. J. Cell. Physiol. 216: 615–620, 2008, © 2008 Wiley‐Liss, Inc.