Substrate utilization for lactate and energy production by heat‐shocked L929 cells

Abstract

The hypothesis that heat shock protein (HSP) induction depends on inhibition of respiration was tested by examining the effects of heat shock o n tricarboxylic acid (TCA) cycle function. In control L929 cell cultures, glucose and exogenous pyruvate were converted primarily to lactate, and glutamine was extensively oxidized, accounting for more than one-half of the calculated ATP production. During heat shock at 42OC, lactate production from all of t h e labeled substrates and total unlabeled lactate production increased significantly while oxygen consumption increased slightly. TCA cycle oxidation of pyruvate decreased during this period while that of glutamine increased. Uncoupling of oxidative phosphorylation caused large increases in oxygen consumption at both 37OC and 42OC, indicating that the capacity of the respiratory chain is not exceeded during heat shock. The net effect of these alterations in substrate utilization were decreased ATP generation and increased NADH utilization. Both I4CO2 and lactate production declined during the 24-h period after cultures were returned to 37OC. On the basis of these data, we conclude that while inhibition of respiration plays no apparent role, other metabolic consequences of heat shock related to energy metabolism may be involved in HSP induction.Although the heat shock response results in dramatic induction of specific proteins and can easily be evoked in cultured cells, the mechanism responsible for activation of the underlying genes is still unknown. The problem is being approached from several directions, including sequencing of the genetic regulatory elements (Hackett and Lis, 1981;Mason et al

Studies on the mechanism by which glutamine and heat shock increase lactate synthesis by l929 cells in the presence of insulin

“…Incubation at 42°C increased lactate production when glutamine was present but not when it was absent. The effect of heat shock on lactate production in the presence of glutamine and high medium pyruvate is similar to that previously found in the absence of insulin (Lanks et al, 1986a). AOA decreased lactate synthesis at 37"C, suggesting that when excess pyruvate is available net reducing equivalent flux is from mitochondria to cytoplasm.…”

Neurochemical and physiological correlates of a critical period of respiratory development in the rat

“…2A). Increased core temperature especially at P13 may reflect a change in hypothalamic regulation, which may increase thyroid hormone levels and raise the basal metabolic rate, or it may reflect an uncoupling of electron transport and oxidative phosphorylation, generating heat (Dussault and Labrie, 1975; Lanks et al, 1986). If the heat generation is at the expense of ATP production, it could result in decreased energy supply for neuronal activity.…”

In vitro effect of extracellular AMP on MCF‐7 breast cancer cells: Inhibition of glycolysis and cell proliferation

“…Adenosine derivatives and its analogs massively influence the intracellular levels of GTP, UTP, CTP, NAD, and NADP (Green and Chan, 1973;Snyder et al, 1978;Bernofsky, 1980;Rapaport, 1980Rapaport, , 1983Rapaport, ,1988Schweinsberg et al, 1981;Nord et al, 1989). The reduction of NADP and NAD can affect several metabolic pathways like glycolysis, glutaminolysis, and the oxidative pentose-phosphate pathway, all of which are essential for cell proliferation and tumor formation (Lopez-Alarcon et al, 1979;Chapman et al, 1981;McKeehan, 1982;Groelke and Amos, 1984;Eigenbrodt et al, 1985;Lanks et al, 1986;Matsuno, 1987;Brand et al, 1987). All three pathways have been employed as targets for chemotherapeutic agents.…”