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)

Pretreatment of the gerbil brain with a 2-min period of sublethal ischemia protects against neuronal damage following a subsequent 3-min period of ischemia, which normally destroys pyramidal neurons in the CA1 region of the hippocampus. To clarify the role of superoxide dismutase (SOD) in this ischemic tolerance, we immunohistochemically investigated the alterations in copper-zinc SOD (CuZnSOD) and manganese SOD (Mn-SOD) in the gerbil hippocampus following 3-min ischemia with or without the first mild ischemia. Normal hippocampus showed an intense CuZnSOD immunostaining in pyramidal neurons but relatively less MnSOD immunostaining. MnSOD, but not CuZnSOD, immunoreactivity increased after the first ischemia. Both CuZnSOD and MnSOD immunoreactivities decreased throughout the hippocampus 4 h after 3 min of ischemia both with and without the first ischemia. The immunostaining recovered in resistant regions (CA3 and dentate gyrus) after 1 day in both groups and in the pretreated CA1 after 2 days. Without pretreatment, however, the immunostaining never recovered in the vulnerable CA1 region. The results suggest that ischemic tolerance is induced in part by enhanced synthesis of MnSOD in the tolerance-acquired hippocampus. Both CuZnSOD and MnSOD immunoreactivities decreased after the second ischemia even in the pretreated hippocampus in the early reperfusion periods, but ischemic tolerance facilitated the recovery from the postischemic reductions in SOD immunoreactivity.
J Cereb Blood Flow Metab 1995 Jan
PMID:Immunohistochemical localization of superoxide dismutase in the hippocampus following ischemia in a gerbil model of ischemic tolerance. 779 39

Preconditioning with sublethal ischemia results in natural tolerance to ischemic stress, where multiple mediators of ischemic damage are simultaneously counteracted. Tumor necrosis factor alpha (TNF-alpha) has been implicated in development of ischemic tolerance. Using cellular models of ischemic tolerance, we have demonstrated that an effector of TNF-alpha-induced preconditioning is ceramide, a sphingolipid messenger in TNF-alpha signaling. TNF-alpha/ceramide-induced preconditioning protected cultured neurons against ischemic death and cultured astrocytes against proinflammatory effects of TNF-alpha. TNF-alpha activates a transcription factor NF-kappaB that binds promoters of multiple genes, thus ensuring pleiotropic effects of TNF-alpha. We describe here a mechanism that allows selective suppression of TNF-alpha/NF-kappaB-induced harmful genes in preconditioned cells while preserving cytoprotective responses. We demonstrate that in astrocytes activation of an adhesion molecule ICAM-1 by TNF-alpha is regulated through association of the phosphorylated p65 subunit of NF-kappaB with an adapter protein, p300, and that in preconditioned cells p65 remains unphosphorylated and ICAM-1 transcription is inhibited. However, TNF-alpha-activated transcription of a protective enzyme, MnSOD, does not depend on p300 and does not become inhibited in preconditioned cells. This new understanding of TNF-alpha-induced adaptation to ischemic stress and inflammation could suggest novel avenues for clinical intervention during ischemic and inflammatory diseases.
J Cereb Blood Flow Metab 2002 Feb
PMID:TNF-alpha-induced tolerance to ischemic injury involves differential control of NF-kappaB transactivation: the role of NF-kappaB association with p300 adaptor. 1182 12

Oxidative stress and excitotoxicity have been implicated in selective striatal vulnerability caused by the mitochondrial toxin, 3-nitropropionic acid (3-NP), which may simulate Huntington's disease in animals and humans. The detailed mechanism of the role of superoxide in striatal vulnerability induced by 3-NP is still unknown. The authors investigated oxidative cellular injury and DNA fragmentation after systemic 3-NP injection in wild-type (Wt) mice and mutant mice with a deficiency in manganese superoxide dismutase (MnSOD; Sod2 -/+). Furthermore, they investigated the effects of decortication after 3-NP treatment in Sod2 -/+ mice, and copper/zinc SOD (CuZnSOD) treatment in recently developed Sod2 -/+ mice that overexpress CuZnSOD (SOD1 +/- / Sod2 -/+ mice). Oxidized hydroethidine, 8-hydroxyguanosine immunoreactivity, and nitrotyrosine immunoreactivity were increased in the Sod2 -/+ mice compared with the Wt mice after 3-NP treatment (P < 0.001). Decortication completely abolished oxidative striatal damage after 3-NP treatment in the Sod2 -/+ mice. Increased CuZnSOD attenuated DNA fragmentation and striatal lesion volume after 3-NP treatment in the Sod2 -/+ mice (P < 0.001). These data suggest that production of superoxide may be a critical step to excitotoxicity and subsequent DNA fragmentation in selective striatal vulnerability after 3-NP treatment.
J Cereb Blood Flow Metab 2002 Jul
PMID:Involvement of superoxide in excitotoxicity and DNA fragmentation in striatal vulnerability in mice after treatment with the mitochondrial toxin, 3-nitropropionic acid. 1214 65

We recently showed that intraischemic moderate hypothermia (30 degrees C) reduces ischemic damage through the Akt pathway after permanent distal middle cerebral artery occlusion in rats. The only Akt pathway component preserved by hypothermia is phosphorylated phosphatase and tensin homolog deleted on chromosome 10 (p-PTEN), which suggests that p-PTEN may have a central role in neuroprotection. Reactive oxygen species (ROS) are critically involved in mediating ischemic damage after stroke by interacting with signaling molecules, including Akt, PTEN, and delta-protein kinase C (PKC). We investigated the protective mechanisms of moderate hypothermia on these signaling proteins after transient focal ischemia in rats. Early moderate hypothermia (3 h) was administered 15 mins before reperfusion, and delayed moderate hypothermia (3 h) was applied 15 mins after reperfusion. Our results indicate that early hypothermia reduced infarction, whereas delayed hypothermia did not. However, both early and delayed hypothermia maintained levels of Mn-SOD (superoxide dismutase) and phosphorylated Akt and blocked delta-PKC cleavage, suggesting that these factors may not be critical to the protection of hypothermia. Nevertheless, early hypothermia preserved p-PTEN levels after reperfusion, whereas delayed hypothermia did not. Furthermore, ROS inhibition maintained levels of p-PTEN after stroke. Together, these findings suggest that phosphorylation levels of PTEN are closely associated with the protective effect of early hypothermia against stroke.
J Cereb Blood Flow Metab 2009 Sep
PMID:The protective effect of early hypothermia on PTEN phosphorylation correlates with free radical inhibition in rat stroke. 1955 7