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)

Preconditioning adaptation induced by transient ischemia can increase brain tolerance to oxidative stress, but the underlying neuroprotective mechanisms are not fully understood. Recently, we developed a human brain-derived cell model to investigate preconditioning mechanism in SH-SY5Y neuroblastoma cells.(1) Our results demonstrate that a non-lethal serum deprivation-stress for 2 h (preconditioning stress) enhanced the tolerance to a subsequent lethal oxidative stress (24 h serum deprivation) and also to 1-methyl-4-phenyl-pyridinium (MPP(+)).(2) Two-hour non-lethal preconditioning stress increased the expression of neuronal nitric oxide (NOS1/nNOS) mRNA, Fos, Ref-1, NOS protein, and then nitric oxide (*NO) production. As well as MnSOD expression, the *NO-cGMP-PKG pathway mediated the preconditioning-induced upregulation of antiapoptotic protein Bcl-2 and the downregulation of adaptor protein p66(shc). We also propose that cGMP-mediated preconditioning-induced adaptation against oxidative stress may be due to the synthesis of a new protein, such as thioredoxin (Trx) since the protective effect can be blocked by Trx reductase inhibitor.(3) The antioxidative potency of Trx was approximately 100 and 1,000 times greater than GSNO and GSH, respectively. These results suggest that *NO-cGMP-PKG signaling pathway plays an important role in the preconditioning-induced neuroprotection, and perhaps cardioprotection, against oxidative stress.
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PMID:Preconditioning-mediated neuroprotection: role of nitric oxide, cGMP, and new protein expression. 1207 58

Mitochondrial dysfunction is involved in the underlying pathology of Parkinson's Disease (PD). PINK1 deficiency, which gives rise to familial early-onset PD, is associated with this dysfunction as well as increased oxidative stress. We have established primary fibroblast cell lines from two patients with PD who carry mutations in the PINK1 gene. The phosphorylation of Akt is abrogated in the presence of oxidative stressors in the complete absence of PINK1 suggesting enhanced apoptotic signalling. We have found an imbalance between the production of reactive oxygen species where the capacity of the cell to remove these toxins by anti-oxidative enzymes is greatly reduced. The expression levels of the anti-oxidant enzymes glutathione peroxidase-1, MnSOD, peroxiredoxin-3 and thioredoxin-2 were diminished. The p66(Shc) adaptor protein has recently been identified to become activated by oxidative stress by phosphorylation at residue Ser36 which then translocates to the mitochondrial inner membrane space. The phosphorylation of p66(Shc) at Ser36 is significantly increased in PINK1 deficient cell lines under normal tissue culture conditions, further still in the presence of compounds which elicit oxidative stress. The stable transfection of PINK1 in the fibroblasts which display the null phenotype ameliorates the hyper-phosphorylation of p66(Shc).
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PMID:Oxidative stress alters the regulatory control of p66Shc and Akt in PINK1 deficient cells. 2063 29

The in vitro production of mammalian embryos suffers from high frequencies of developmental failure due to excessive levels of permanent embryo arrest and apoptosis caused by oxidative stress. The p66Shc stress adaptor protein controls oxidative stress response of somatic cells by regulating intracellular ROS levels through multiple pathways, including mitochondrial ROS generation and the repression of antioxidant gene expression. We have previously demonstrated a strong relationship with elevated p66Shc levels, reduced antioxidant levels and greater intracellular ROS generation with the high incidence of permanent cell cycle arrest of 2-4 cell embryos cultured under high oxygen tensions or after oxidant treatment. The main objective of this study was to establish a functional role for p66Shc in regulating the oxidative stress response during early embryo development. Using RNA interference in bovine zygotes we show that p66Shc knockdown embryos exhibited increased MnSOD levels, reduced intracellular ROS and DNA damage that resulted in a greater propensity for development to the blastocyst stage. P66Shc knockdown embryos were stress resistant exhibiting significantly reduced intracellular ROS levels, DNA damage, permanent 2-4 cell embryo arrest and diminished apoptosis frequencies after oxidant treatment. The results of this study demonstrate that p66Shc controls the oxidative stress response in early mammalian embryos. Small molecule inhibition of p66Shc may be a viable clinical therapy to increase the developmental potential of in vitro produced mammalian embryos.
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PMID:The p66(Shc) adaptor protein controls oxidative stress response in early bovine embryos. 2447 5