TY - JOUR
T1 - Alanine protects rabbit proximal tubules against toxic injury in vitro
AU - Garza-Quintero, R.
AU - Ortega-Lopez, J.
AU - Stein, J. H.
AU - Venkatachalam, M. A.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1990
Y1 - 1990
N2 - Rabbit proximal tubules were incubated aerobically or subjected to anoxia for 30 min followed by 60 min of reoxygenation. The medium contained (in mM) 5 glucose, 10 butyrate, 4 lactate or α-ketoglutarate (α-KG), and 1 alanine. Anoxic tubules in this medium were severely injured and recovered poorly. If the incubation medium was supplemented with additional alanine (up to 2.5 or 5 mM), then anoxic injury was prevented almost completely. Tubules in high-alanine medium showed modest elevations of ATP during anoxia. Comparable elevations of ATP were induced in anoxic tubules incubated with 4 mM α-KG and 5 mM aspartate without alanine. These substrates are metabolized anaerobically in the mitochondria to yield ATP. Surprisingly, anoxic tubules with α-KG and aspartate showed severe injury despite elevated ATP. If 5 mM alanine was also present, then additional increments of ATP did not occur, but injury was prevented. Examination of glucose metabolism failed to provide evidence for stimulation of anaerobic fermentations by alanine. These results suggest that alanine-induced cytoprotection during anoxia occurs by mechanisms not related to ATP synthesis, and that elevated ATP in alanine-supplemented tubules may be a result and not the cause of protection. Cytoprotection by alanine was shown to last for ≤90 min of anoxia. Glycine, a structurally related amino acid, also protects anoxic proximal tubules.
AB - Rabbit proximal tubules were incubated aerobically or subjected to anoxia for 30 min followed by 60 min of reoxygenation. The medium contained (in mM) 5 glucose, 10 butyrate, 4 lactate or α-ketoglutarate (α-KG), and 1 alanine. Anoxic tubules in this medium were severely injured and recovered poorly. If the incubation medium was supplemented with additional alanine (up to 2.5 or 5 mM), then anoxic injury was prevented almost completely. Tubules in high-alanine medium showed modest elevations of ATP during anoxia. Comparable elevations of ATP were induced in anoxic tubules incubated with 4 mM α-KG and 5 mM aspartate without alanine. These substrates are metabolized anaerobically in the mitochondria to yield ATP. Surprisingly, anoxic tubules with α-KG and aspartate showed severe injury despite elevated ATP. If 5 mM alanine was also present, then additional increments of ATP did not occur, but injury was prevented. Examination of glucose metabolism failed to provide evidence for stimulation of anaerobic fermentations by alanine. These results suggest that alanine-induced cytoprotection during anoxia occurs by mechanisms not related to ATP synthesis, and that elevated ATP in alanine-supplemented tubules may be a result and not the cause of protection. Cytoprotection by alanine was shown to last for ≤90 min of anoxia. Glycine, a structurally related amino acid, also protects anoxic proximal tubules.
KW - adenosinetriphosphate
KW - anaerobic glucose metabolism
KW - glycine
KW - membrane damage
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M3 - Article
C2 - 2330973
AN - SCOPUS:0025257039
VL - 258
SP - F1075-F1083
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 0363-6127
IS - 4 27-4
ER -