Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mammalian antizyme (AZ) promotes ubiqutin-independent degradation of ornithine decarboxylase, a key enzyme in polyamine biosynthesis. This study shows that AZ suppression in human lung carcinoma A549 cells caused growth defects and death, but made the cells resistant to DNA damaging agents such as gamma-radiation and cisplatin. In these cells, the cellular redox potential (glutathione/glutathione disulfide [GSH/GSSG] ratio) was increased and thus intracellular reactive oxygen species were severely diminished, which might cause growth defects and cell death. The increase of cellular redox potential was mainly caused by dramatic increase of the cytoplasmic nicotinamide adenine dinucleotide phosphate (NADP)(+)-dependent isocitrate dehydrogenase, which generates the reducing equivalents NADPH. In the AZ-suppressed cells, the hypoxia inducible factor 1alpha (HIF-1alpha) was also increased. As in other cases which showed an increment of HIF-1alpha and the cellular redox potential, the AZ-suppressed cells showed resistance to gamma-radiation and anticancer drugs. Therefore, these facts might be considered as important for the use of radio- and chemotherapy on tumor cells which show an unbalance in their polyamine levels.
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PMID:Antizyme suppression leads to an increment of the cellular redox potential and an induction of HIF-1alpha: its involvement in resistance to gamma-radiation. 1848 90

Acrolein is known to be involved in acute lung injury and other pulmonary diseases. A number of studies have suggested that acrolein-induced toxic effects are associated with depletion of antioxidants, such as reduced glutathione and protein thiols, and production of reactive oxygen species. Mitochondrial NADP+-dependent isocitrate dehydrogenase (idh2) regulates mitochondrial redox balance and reduces oxidative stress-induced cell injury via generation of NADPH. Therefore, we evaluated the role of idh2 in acrolein-induced lung injury using idh2 short hairpin RNA- (shRNA-) transfected Lewis lung carcinoma (LLC) cells and idh2-deficient (idh2-/- ) mice. Downregulation of idh2 expression increased susceptibility to acrolein via induction of apoptotic cell death due to elevated mitochondrial oxidative stress. Idh2 deficiency also promoted acrolein-induced lung injury in idh2 knockout mice through the disruption of mitochondrial redox status. In addition, acrolein-induced toxicity in idh2 shRNA-transfected LLC cells and in idh2 knockout mice was ameliorated by the antioxidant, N-acetylcysteine, through attenuation of oxidative stress resulting from idh2 deficiency. In conclusion, idh2 deficiency leads to mitochondrial redox environment deterioration, which causes acrolein-mediated apoptosis of LLC cells and acrolein-induced lung injury in idh2-/- mice. The present study supports the central role of idh2 deficiency in inducing oxidative stress resulting from acrolein-induced disruption of mitochondrial redox status in the lung.
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PMID:Idh2 Deficiency Exacerbates Acrolein-Induced Lung Injury through Mitochondrial Redox Environment Deterioration. 2945 84