CHANGES IN PULMONARY EXPRESSION OF HEXOKINASE AND GLUCOSE-TRANSPORTERMESSENGER-RNAS IN RATS ADAPTED TO HYPEROXIA

Impairment of lung aconitase activity, citric acid cycle, and mitochon drial respiration by hyperoxia necessitates the elevation of glycolysi s for energy production and of pentose shunt activity for reducing equ ivalents. The molecular mechanisms that allow increased glucose utiliz ation are unknown. Adult male and female rats were adapted to subletha l hyperoxia, equivalent to 83% oxygen at sea level, or air for 7 days. Lung RNA and protein increased in hyperoxia (197 and 57%, respectivel y), whereas total DNA was unchanged. In hyperoxia, lung total hexokina se (HX) activity increased threefold, and mRNAs for HK-II and -III wer e specifically upregulated. HK-I mRNA was unchanged. mRNAs for HK-II a nd -III gradually increased during the first 72 h in hyperoxia. HK-II mRNA was significantly elevated at 72 h, preceding changes in lung cel l populations. Although virtually absent in air, HK-II activity was hi ghly expressed in hyperoxia. Among lung glucose transporters, specific expression of mRNAs for GLUT-4 (insulin dependent) and sodium-glucose cotransporter-1 was decreased, whereas that for GLUT-1 was minimally changed. Adaptation to hyperoxia involves coordinated changes in gene expression for the proteins regulating pulmonary glucose transport.