Role of glycolysis in the maintenance of the energy-synthesizing function of hepatocytes from rats adapted and nonadapted to hypoxia at different oxygen concentrations

Abstract

It is demonstrated that the lactate-P0:dependence is the same in hepatocytes of rats with high and low resistance to hypoxia and does not correlate with phasic changes in the ATP concentration in the 890-50 ~tM 02 region. Strong activation of lactate formation against the background of ATP decrease indicates that glycolysis is not the major mechanism determining the steady-state ATP level in the cell and affecting the ATP-P0~ relationship in a wide range of oxygen concentrations. The intensity of glycolysis in hepatocytes of rats with high resistance to hypoxia is markedly increased after periodic adaptation to hypoxia but remains practically unchanged in the hepatocytes of low-resistance rats. This indicates that fundamentally different compensatory mechanisms are involved in this process in the liver of high-and low-resistance rats.Key Words: hepatocytes; glycolysis; lactate; ATP; adaptation; hypoxia Glycolysis and oxidative phosphorylation are two regulatory mechanisms controlling and determining the energy-synthesizing function of the cell. Under conditions of oxygen deficiency, the reduction in the intensity of the aerobic component is compensated by the activation of glycolysis. Therefore, increased lactate production at lowered oxygen concentration in the medium reflects the intensity of glycolysis and can be employed as a prognostic criterion for the evaluation of hypoxia, characterizing the contribution of the anaerobic process to energy formation. Analysis of the dynamics of this process in oxygen deficiency is hence of prime importance. Since brain tissues are highly sensitive to hypoxia, the role of glycolysis in hypoxia has been studied predominantly in the brain. On the other hand, the specific features of alterations Laboratory of Bioenergetics, Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow in the energy-synthesizing function of the liver and the role of glycolysis in this process in hypoxia have been poorly investigated, even though hepatic ischemia is a major cause of liver pathologies. In view of all this, we decided to explore how glycolysis aids in allowing the energy-synthesizing function of isolated hepatocytes incubated under varied conditions of oxygenation develop resistance to oxygen deficiency.