Effect of hyperoxia on the carbohydrate metabolism of human lymphocytes

Abstract

Lymphocytes incubated under high oxygen tensions have impaired lymphoblastic transformation to nonspecific mitogens. Since carbohydrate metabolism may be essential for an optimal proliferation of these cells following an antigenic stimulus, we have characterized the effect of hyperoxia on the glucose metabolism of human lymphocytes in vitro. The mean rates of glucose utilization, Krebs cycle activity, and hexose monophosphate shunt activity were determined for unstimulated and phytohemagglutinin (PHA)-stimulated cultures incubated for 3 days. In unstimulated cultures, hyperoxia stimulated glucose utilization and markedly impaired Krebs cycle activity but did not alter HMPS activity. These observations suggest that hyperoxia impairs the mitochondrial activity of lymphocytes and that increased glycolysis compensates for the loss of cellular energy normally produced by this organelle. Under high oxygen tension PHA-stimulated cultures failed to show the burst in HMPS activity and increased Krebs cycle activity characteristic of cultures incubated under physiological oxygen tensions and consumed less glucose. Our results indicate that hyperoxia alters the glucose metabolism of lymphocytes. This metabolic alteration may be related to the impaired function of the cells under hyperoxic conditions.

13C-Metabolic flux analysis detected a hyperoxemia-induced reduction of tricarboxylic acid cycle metabolism in granulocytes during two models of porcine acute subdural hematoma and hemorrhagic shock

“…Sagone et al. suggested impaired mitochondrial activity in lymphocytes by hyperoxia, although our results did not replicate the effect of hyperoxia on i) glycolysis, ii) mitochondrial respiration, and iii) other lymphocyte subsets ( 55 ). Nevertheless, our study suggests a specific inhibition of TCA cycle acceleration in circulating granulocytes in response to ASDH and HS, without affecting mitochondrial respiration.…”

Evolution of Air Breathing: Oxygen Homeostasis and the Transitions from Water to Land and Sky

“…As a result, the primordial anoxic conditions of the Earth necessary for survival and optimal function of this proteobacterial remnant are preserved inside the host cell. In working human leg muscle O 2 tension at the sarcoplasmic and mitochondrial boundaries has been estimated at approximately 2.4 mmHg (0.32 kPa) (835) and muscle mitochondrial O 2 concentration at half-maximal metabolic rate 0.02 to 0.2 mmHg (834), that is, in the range of the ancient atmospheric level approximately 2 Ga. Raising O 2 tension above these levels impairs mitochondrial activity (672). In this context, protection of mitochondria from O 2 exposure likely constitutes a major selection factor in the evolution of complex aerobic life while the various forms of systemic O 2 delivery systems are necessary but secondary functions that sustain the “gate-keeping” barrier apparatus to maintain adequate partial pressure gradients along the O 2 transport cascade and preserve the near-anoxic intracellular conditions for the mitochondria.…”