Oxygen stress effects on proliferation rates and heat shock proteins in lymphocytes

High-oxygen conditions produce oxidants and cause some pathognomonic signs and symptoms in human hosts. However, the biological effects at the cellular level are still unclear. To investigate the cellular response against oxygen stress, we measured the proliferative activity and heat shock protein (HSP) expression of human lymphocytes.

Hydrogen peroxide (H2O2) was used as a source of reactive oxygen species. The time course of the proliferative/apoptotic response was evaluated from DNA histogram analysis. HSP response was measured by Western blot analysis.

Suppression of lymphocyte cluster formation by oxygen stress was observed to be dose-dependent. Induction of apoptotic cell death and retardation of entering the S-phase were also affected according to the extent of oxygen stress. Oxygen stress equivalent to 500 micromol x L(-1) H2O2 or more showed a severe impairment of the cell cycle and that equivalent to 50-100 micromol x L(-1) H2O2 revealed an intermediate effect. Although an increased expression of HSP72/73 was observed in each group 6 h after oxygen stress, only 100 micromol x L(-1) H2O2-treated cells remained at a high expression level after 24 h.

It is likely that when cells encounter oxygen stress, an increased expression of HSP72/73 and subsequent repair of damaged proteins cause the retardation of cell cycle progression and prevent damaged cells from entering the S phase. But if the damage is too strong, the cells may go into apoptotic cell death. From our results of the HSP72/73 experiment, the threshold that determines the fate of the lymphocytes may be around 100 micromol x L(-1) H2O2.