Energetic stress in combination with tumor necrosis factor-alpha (TNF-alpha) induces apoptosis of human fibroblasts (WI-38) in vitro: reduced responsiveness of senescent cells.

Abstract

The NaCl content of the culture medium of human fibroblasts (WI-38) was elevated from 0.12 M to 0.23 M. Previously it had been shown that exposure of fibroblasts to such high NaCl conditions resulted in a rise of both glycolysis and respiration ("energetic stress"), mainly due to increased demands of energy for active ion transport ("sodium pump"). While "young" (Phase II) and "senescent" (Phase III) cells did not show a significant increase of apoptosis over the basal rate (ca. 4%) under treatment with either a high-NaCl medium or TNF-alpha (10 nM) alone, combined treatment resulted in a strong increase in Phase II cells and a significantly lesser rise in the case of "senescent" Phase III cells. We conclude, therefore, that energetic stress stimulates sensitivity to apoptosis by (in the presence of) TNF-alpha, especially pronounced in potentially replicating "young" as compared with irreversible postmitotic ("senescent") fibroblasts. Possible causes of this differential responsiveness and implications for the in vivo situation (in the organism) were discussed.