AJP - Cell Physiology, Vol 258, Issue 6 C1127-C1140, Copyright © 1990 by American Physiological Society
Protection by glycine of proximal tubules from injury due to inhibitors of mitochondrial ATP production
J. M. Weinberg, J. A. Davis, M. Abarzua, T. Kiani and R. Kunkel
Department of Internal Medicine, Veterans Administration Medical Center, Ann Arbor, Michigan.
We have determined whether glycine or glutathione can protect rabbit
proximal tubules damaged by chemical inhibitors of oxidative
phosphorylation: antimycin A, rotenone, cyanide, oligomycin, or carbonyl
cyanide m-chlorophenylhdrazone (CCCP). All the agents severely depleted
cell ATP levels within 15 min and caused lethal cell injury, as quantified
by lactate dehydrogenase (LDH) release. Glycine and glutathione largely
prevented this injury without altering the primary effects of the
inhibitors on tubule respiration or the depletion of ATP. Buthionine
sulfoximine and 1,3-bis(2-chloroethyl)-1-nitrosourea decreased cell
glutathione but did not prevent the protective effects of either glycine or
glutathione in tubules treated with rotenone. Protection was sustained
during both a 15-min exposure and a 45-min postwash period irrespective of
whether the wash removed the agent or mitochondrial function recovered.
Cysteine uniquely induced a dramatic recovery of mitochondrial function in
tubules washed after treatment with CCCP. These data 1) demonstrate that
the cytoprotective effects of glycine previously seen during hypoxia extend
to other tubule lesions characterized by severe ATP depletion, 2) emphasize
the actions of glycine to preserve cell structural integrity in spite of
sustained severe impairment of ATP-generating processes in proximal
tubules, and 3) indicate that it is glycine rather than intracellular or
extracellular glutathione which mediates protection.
