By using a gel mobility assay, we have shown that treatment of HeLa cells with 4-hydroxynonenal, a major product of the peroxidation of membrane lipids and an inducer of heat-shock proteins, has the same effect as heat shock in causing the appearance of a protein which binds to the sequence of DNA specific for the induction of heat-shock genes. Lipoperoxidation and heat exposure seem to share a common mechanism of specific gene activation.
1. The concentrations of some phosphorylated glycolytic intermediates and of NADH were measured in glycolysing rat liver slices. 2. In anaerobically incubated liver slices the concentration of hexose monophosphates decreases during the first 20min. of incubation, whereas the concentrations of fructose diphosphate and triose phosphates increase progressively. 3. In liver slices from fed rats, previously exposed to oxygen, the stimulated anaerobic glycolysis is accompanied by an increase in the concentration of hexose monophosphates; fructose diphosphate and triose phosphates maintain the concentrations reached at the end of the aerobic preincubation. 4. The same pattern in the concentration of glycolytic phosphorylated intermediates is seen under all conditions where aerobic preincubation brings about a stimulation of anaerobic glycolysis. A similar pattern is also found in liver slices from fed rats incubated anaerobically in the presence of fructose; these slices display a high glycolytic activity, which is not further affected by previous aerobic incubation. 5. The concentration of NADH decreases in liver slices during exposure to oxygen; during the subsequent anaerobic glycolysis the concentration increases but is always lower in preincubated than in non-preincubated liver slices. 6. The results of the present experiments suggest that the limiting step mainly affected by the preliminary exposure to oxygen might be at the level of the utilization of triose phosphates.
1. A short period of incubation in oxygen increases the rate of anaerobic glycolysis in all the normal adult tissues that have been tested, with the exception of erythrocytes. 2. This stimulation does not occur in the six different tumours and in the two embryonic tissues that have been studied. 3. In rat liver and in chicken heart, stimulation is first seen at birth. 4. Stimulation in rat liver slices is decreased in the presence of some inhibitors of oxidative metabolism (cyanide, Amytal, dinitrophenol, malonate), but is not affected if the aerobic preincubation is carried out at 1°. 5. The presence in the medium of some metabolites that are known to be important regulators of the glycolytic rate in living tissues has essentially no effect on stimulation. 6. The pretreatment of animals with inhibitors of oxidative metabolism and with antioxidants does not suppress stimulation; the observed effect of NN ′-diphenyl- p -phenylenediamine is probably the consequence of the fall of the glycogen content in the liver. 7. The stimulation of anaerobic glycolysis by previous aerobiosis could not be demonstrated in liver homogenates.