We have investigated biochemical mechanism of signaling in cultured human skin fibroblasts and hepatocytes. We found that TNF-α or mutated TNF-α peptides that specifically activate either the p55 or p75 receptors can activate neutral sphingomyelinase (N-SMase). This phenomena observed in hepatocytes was accompanied by a time-dependent activation of LDL receptors. Significant increase in LDL receptor occurred within 15-30 minutes of incubation of cells with TNF-α and mutant peptides. Maximum increase (2-fold) in LDL receptor occurred 3 hours after incubation with agonists. In fibroblasts, TNF-α and p55, TNF-α mutant but not p75 TNF-α mutant stimulated N-SMase activity, LDL binding and cholesteryl ester synthesis. The relatively low affinity of fibroblast p75 receptors for the p75 mutants may explain the observation above. In sum, induction of LDL receptor by TNF-α might be mediated through N-SMase.
|Original language||English (US)|
|State||Published - Dec 1 1996|
ASJC Scopus subject areas
- Molecular Biology