Metabolic inhibition potentiates oxidant injury
dc.contributor.author | Delius, Ralph E. | en_US |
dc.contributor.author | Hinshaw, Daniel B. | en_US |
dc.date.accessioned | 2006-04-10T14:46:11Z | |
dc.date.available | 2006-04-10T14:46:11Z | |
dc.date.issued | 1991-04 | en_US |
dc.identifier.citation | Delius, Ralph E., Hinshaw, Daniel B. (1991/04)."Metabolic inhibition potentiates oxidant injury." Journal of Surgical Research 50(4): 314-322. <http://hdl.handle.net/2027.42/29401> | en_US |
dc.identifier.uri | http://www.sciencedirect.com/science/article/B6WM6-4BNG3RX-10V/2/e22613cab40fe73de975d7f5f6de59e2 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/29401 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=2020185&dopt=citation | en_US |
dc.description.abstract | Toxic oxygen species have been implicated as important mediators of injury after reperfusion of an ischemic organ. The aim of this study was to determine if prior metabolic inhibition, such as that which occurs during ischemia, potentiates oxidant injury in vitro. Bovine pulmonary artery endothelial cells were metabolically inhibited for various periods of time with or without the mitochondrial inhibitor oligomycin (650 nM). The cells were rescued from metabolic inhibition by a wash step and subsequent addition of 5.5 mM glucose. At the same time that metabolic inhibition was relieved the cells were subjected to doses of H2O2 ranging from 0 to 100 [mu]M. ATP levels were monitored over a 2-hr time course after rescue from metabolic inhibition by the luciferin--luciferase assay. Cell viability at 2 hr after relief of metabolic inhibition was assessed by trypan blue exclusion. Intracellular pH during metabolic inhibition was determined with the fluorescent dye 2',7'-bis-(2-carboxyethyl)-5(and-6) carboxyfluorescein tetraacetomethoxymethyl ester. H2O2 consumption, a measure of H2O2 scavenging capability, was determined by a fluorescent assay. The viability and ATP levels of cells not subjected to metabolic inhibition were unaffected by these low concentrations of H2O2. Cells metabolically inhibited with glucose depletion and oligomycin were exquisitely sensitive to H2O2. Cells that were only deprived of glucose demonstrated no potentiation of injury, while cells subjected to mitochondrial inhibition with oligomycin alone also showed significant potentiation of oxidant injury. H2O2 consumption was not affected by metabolic inhibition. Conditions associated with mitochondrial inhibition consistently resulted in a decrease in intracellular pH. These experiments suggest that a synergism exists between metabolic inhibition and subsequent oxidant exposure. This synergism is dependent on inhibition of mitochondrial function but is independent of ATP levels. Intracellular acidosis correlated well with conditions which potentiated oxidant injury. | en_US |
dc.format.extent | 1032609 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.title | Metabolic inhibition potentiates oxidant injury | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Surgery and Anesthesiology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Surgical Service, Ann Arbor Veterans Administration Medical Center, Department of Surgery, University of Michigan, Ann Arbor, Michigan 48105, USA | en_US |
dc.contributor.affiliationum | Surgical Service, Ann Arbor Veterans Administration Medical Center, Department of Surgery, University of Michigan, Ann Arbor, Michigan 48105, USA | en_US |
dc.identifier.pmid | 2020185 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/29401/1/0000474.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1016/0022-4804(91)90197-T | en_US |
dc.identifier.source | Journal of Surgical Research | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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