Glycolysis is not responsible for the tolerance of immature renal tubules to anoxia

We have previously shown that the immature tubule is tolerant of prolonged anoxia. In addition, cellular ATP is maintained at 2-fold higher levels during anoxia in the immature tubules compared with the mature tubules. The purpose of this study was: 1) to determine whether anaerobic glycolysis contributes to the tolerance to anoxia and preservation of cellular ATP in immature tubules and 2) to evaluate whether the tolerance demonstrated by immature tubules is dependent on preservation of cellular ATP. Suspensions of proximal tubules from immature (8-10 d) and mature (8-10 wk) rats were subjected to 15 and 45 min of anoxia in a standard buffer and in buffers designed to inhibit glycolysis. Lactate dehydrogenase release was used to assess plasma membrane damage, ATP levels were determined as an index of cellular energy and total lactate production was measured to evaluate glycolytic activity. After 45 min of anoxia, total lactate production was less in immature tubules (101 +/- 48 mu g of lactate/mg of DNA) compared with mature tubules (148 +/- 36 mu g of lactate/mg of DNA). After inhibition of glycolytic metabolism, ATP decreased to similar levels in both immature and mature tubules. However, immature tubules remained resistant to anoxic damage (lactate dehydrogenase: mature tubules 38 +/- 4%, immature tubules 29 +/- 1.0%). Therefore, enhanced glycolytic activity does not play a dominant role in the tolerance of the developing kidney to anoxia, and this tolerance is not primarily dependent on preservation of cellular ATP.