Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human vascular endothelial cells play a pivotal role in atherosclerotic changes but are resistant to apoptotic inducers such as Fas ligand and it has been difficult to induce apoptosis. We developed an experimental model for the apoptosis in the endothelial cells by using snake venom treatment. Snake venom was found to generate intracellular reactive oxygen species (ROS) in the endothelial cells, which leads to apoptosis as judged by electron microscopy as well as by DNA cleavage. Buthionine sulfoximine (BSO) and diethyldithiocarbamate (DDC) accelerated the apoptosis, indicating intracellular glutathione and superoxide levels play a critical role. Pretreatment with tumor necrosis factor (TNF) or phorbol ester (TPA), which increases the Mn-SOD level, prevented the apoptosis. These data suggest that intracellular ROS enhances apoptosis whereas several anti-oxidants are protective in human endothelial cells. The induction of apoptosis by ROS of endothelial cells may be related to initiation of atherosclerotic changes.
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PMID:Induction of apoptotic cell death in human endothelial cells treated with snake venom: implication of intracellular reactive oxygen species and protective effects of glutathione and superoxide dismutases. 949 74

To study whether and how cells adapt to chronic cellular stress, we exposed PC12 cells to the proteasome inhibitor MG132 (0.1 microM) for 2 weeks and longer. This treatment reduced chymotrypsin-like proteasome activity by 47% and was associated with protection against both 6-hydroxydopamine (6-OHDA; 100 microM) and higher dose MG132 (40 microM). Protection developed slowly over the course of the first 2 weeks of exposure and was chronic thereafter. There was no change in total GSH levels after MG132. Buthionine sulfoximine (100 microM) reduced GSH levels by 60%, but exacerbated 6-OHDA toxicity to the same extent in both MG132-treated and control cells and failed to reduce MG132-induced protection. Chronic MG132 resulted in elevated antioxidant proteins CuZn superoxide dismutase (SOD; +55%), MnSOD (+21%), and catalase (+15%), as well as chaperone heat-shock protein 70 (+42%). Examination of SOD enzyme activity revealed higher levels of CuZnSOD (+40%), with no change in MnSOD. We further assessed the mechanism of protection by reducing CuZnSOD levels with two independent siRNA sequences, both of which successfully attenuated protection against 6-OHDA. Previous reports suggested that artificial over-expression of CuZnSOD in dopaminergic cells is protective. Our data complement such observations, revealing that dopaminergic cells are also able to use endogenous CuZnSOD in self-defensive adaptations to chronic stress, and that they can even do so in the face of extensive GSH loss.
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PMID:Adaptation to chronic MG132 reduces oxidative toxicity by a CuZnSOD-dependent mechanism. 1846 18