Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Early events in the cytotoxic response to tumour necrosis factor (TNF) of the murine fibrosarcoma cell lines L929 and WEHI164cl13 were assessed on a cell by cell basis using the fluorescent exclusion dye propidium iodide (PI) and analysis by flow cytometry. The rationale of this approach is based on the exclusion of PI by cells with intact membranes. PI-positive cells appeared within a few hours of TNF treatment and further accumulated with time at a TNF dose-dependent rate. Thus, TNF rapidly caused a breakdown of the barrier function of the membrane in these TNF-sensitive fibrosarcoma cell lines. On a time basis, membrane permeabilization was immediately followed by a sudden shrinkage of the cell and was accompanied by cell death, but preceded the inactivation of the mitochondrial succinate dehydrogenase by several hours. The latter enzymatic activity was measured by the MTT chromogenic assay. Cell death was determined on the basis of the capability of individual cells to produce a progeny in a clonogenicity assay. Both membrane permeabilization and cellular collapse were fast events that were completed within a very short time and may represent the direct cause for cell death. Opposed to this, loss of mitochondrial succinate dehydrogenase activity evolved more slowly, was initiated at a later time and apparently represents a post-lethal event, not directly linked to the TNF signal transduction pathway. Finally, the enhancing effect of the protein synthesis inhibitor cycloheximide on the various features of TNF-induced cytotoxicity was determined.(ABSTRACT TRUNCATED AT 250 WORDS)
Cytokine 1993 Nov
PMID:Cell membrane permeabilization and cellular collapse, followed by loss of dehydrogenase activity: early events in tumour necrosis factor-induced cytotoxicity. 818 66

Cytokine-stimulated astrocytes produce nitric oxide (NO), which, along with its metabolite peroxynitrite (ONOO(-)), can inhibit components of the mitochondrial respiratory chain. We used astrocytes as a source of NO/ONOO(-) and monitored the effects on neurons in coculture. We previously demonstrated that astrocytic NO/ONOO(-) causes significant damage to the activities of complexes II/III and IV of neighbouring neurons after a 24-h coculture. Under these conditions, no neuronal death was observed. Using polytetrafluoroethane filters, which are permeable to gases such as NO but impermeable to NO derivatives, we have now demonstrated that astrocyte-derived NO is responsible for the damage observed in our coculture system. Expanding on these observations, we have now shown that 24 h after removal of NO-producing astrocytes, neurons exhibit complete recovery of complex II/III and IV activities. Furthermore, extending the period of exposure of neurons to NO-producing astrocytes does not cause further damage to the neuronal mitochondrial respiratory chain. However, whereas the activity of complex II/III recovers with time, the damage to complex IV caused by a 48-h coculture with NO-producing astrocytes is irreversible. Therefore, it appears that neurons can recover from short-term damage to mitochondrial complex II/III and IV, whereas exposure to astrocytic-derived NO for longer periods causes permanent damage to neuronal complex IV.
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PMID:Astrocyte-derived nitric oxide causes both reversible and irreversible damage to the neuronal mitochondrial respiratory chain. 1089 44