Department of Medicine, Stanford University School of Medicine, and the Palo Alto Veterans Administration Hospital, Stanford, California 94305
Department of Medicine, Stanford University School of Medicine, Stanford, California 94305
W. Alton Jones Cell Science Center, Lake Placid, New York 12946
Published May 1, 1978 - More info
The bioenergetic pattern of a cell clone derived from rat lung with ultrastructural and biochemical characteristics like those of type II pneumocytes (T-II-P), has been studied in a tissue culture system. During air cultivation, these cells have a high rate of aerobic and anaerobic glycolysis associated with high activities of two rate-limiting enzymes in glycolysis (pyruvate kinase [PyKi] and phosphofructokinase [PFK]). This is present despite the rates of oxygen consumption and activities of cytochrome oxidase (CyOx) similar to other lung cells. Presumably the high rate of aerobic glycolysis explains the substantial lactate production previously described in lung slices and in the intact perfused lung.
Hypoxic cultivation results in a decrease in CyOx. Acute re-exposure to air does not restore the oxygen consumption to normal, presumably as a result of decreased mitochondrial O2 utilization associated with decreased CyOx activity. As a result, hypoxically cultivated T-II-P cells have a decreased capacity for mitochondrial ATP generation in air as compared to air-cultivated cells. During hypoxia, aerobic and anaerobic glycolysis are further increased as well as the activities of PyKi and PFK.
The high rate of glycolysis and high activities of PyKi and PFK in cultivated T-II-P appear to reflect intrinsic genetic regulation. The decreased CyOx activity and increased PyKi and PFK activities in hypoxic T-II-P appear to reflect alterations in enzyme biosynthesis/biodegradation regulated by O2 availability.