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

Hypoxic injury of rat astroglial cells in primary culture initiates several modifications of their functional integrity. A significant decrease of the cellular oxygen consumption was observed in astrocytes submitted to a 15 h low oxygen pressure. The addition of almitrine (dialylamino-4',6'-triazinyl 2')-1-(bis-parafluorobenzydryl)-4-piperazine, a chemoreceptor agonist, restored almost completely the respiratory activity of the hypoxia treated cells. In order to test the hypothesis that oxygen free radical formation may contribute to the cellular damage resulting from ischemia, the activities of the following antioxidant enzymatic systems have been determined in the cultured astrocytes: Cu,Zn- and Mn-superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), glutathione reductase (GSH-RED), and catalase (CAT). Only a significant and specific decrease of the Mn-SOD activity was observed after the hypoxia-normoxia exposure. The other oxygen radical scavenging systems were not modified. The addition of almitrine antagonized the decrease of the Mn-SOD activity observed in the low oxygen pressure treated cells, but results clearly point-out the importance of oxygen radical production in the astroglial response after hypoxic injury. A beneficial effect of almitrine toward the observed alteration has been underlined. It is suggested that some mitochondrial alterations could be related to some aspects of the astroglial hypoxic stress.
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PMID:Free radical scavenging systems of rat astroglial cells in primary culture: effects of anoxia and drug treatment. 140 63

During reperfusion of ischemic brain tissue, the production of reactive oxygen species initiates several modifications of the astroglial functional and ultrastructural integrity. During 24 h after ischemic treatment, modification of cellular superoxide free radical scavenging systems have been observed in primary culture of rat astroglial cell. Mitochondrial Mn superoxide dismutase activity (Mn-SOD) gradually decreases, whereas that of the cytosolic Cu,Zn form of the enzyme remains unaffected. We observed in parallel a significant decrease of glutamine synthetase (GS), an astrocyte specifically located enzyme. Addition of almitrine (dialylamine-4',6'-triazinyl 2')-1-(bis-parafluoro-benzydryl)-4-piperazine or dibucaine (a phospholipase A2 inhibitor) antagonizes the decrease of Mn-SOD activity, but does not affect modification of GS activity. Combined effects are observed by simultaneous addition of both drugs. Our data demonstrate that almitrine may increase the synthesis of some mitochondrial proteins, like Mn-SOD, and provide support for further study on the therapeutic potential of almitrine in ischemic astroglial cell injury.
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PMID:Almitrine prevents some hypoxia-induced metabolic injury in rat astrocytes. 790 67

It has been reported that cellular oxidative stress induces apoptosis, that may be inhibited by scavengers of reactive oxygen intermediates (ROIs). Superoxide dismutase (SOD) is among the most active scavengers of ROIs, providing defense against the cellular oxidative stress. Fas antigen and tumor necrosis factor (TNF) receptor are the cell surface proteins, stimulation of which induces apoptosis of keratinocytes. Using SV40-transformed human keratinocytes (SVHK cells), we investigated the effects of anti-Fas antibody and TNF-alpha on the SOD activity. Treatment of SVHK cells with anti-Fas antibody or TNF-alpha in the presence of interferon-gamma (IFN-gamma) resulted in an increase in Mn-SOD activity, Cu,Zn-SOD activity was not affected. In the absence of IFN-gamma, no increase in Mn-SOD activity was detected. The induction of IFN-gamma-dependent Mn-SOD activity by anti-Fas antibody or TNF-alpha was concentration-dependent; the maximal effect was observed at 1-10 micrograms/ml and 5-10 ng/ml, respectively. The increase in Mn-SOD activity was observed at 6 h following the treatment and remained for at least 48 h. Northern blot analyses showed that Mn-SOD mRNA increased within 3 h without a significant change in Cu,Zn-SOD mRNA. The addition of both anti-Fas antibody and TNF-alpha in the presence of IFN-gamma resulted in an additive increase in Mn-SOD activity. Although the addition of 12-o-tetradecanoylphorbol-13-acetate (TPA) singly to the incubation medium had no effect on either Mn-, or Cu,Zn-SOD activity, it significantly augmented the IFN-gamma-dependent induction of Mn-SOD activity by anti-Fas antibody or by TNF-alpha. The protein kinase C inhibitor, 1-(5-isoquinoline-sulfonyl)-2-methyl piperazine dihydrochloride (H-7), significantly inhibited the TPA-dependent increase in Mn-SOD activity. These results indicate that the stimulation of Fas antigen or TNF receptor increases Mn-SOD activity of SVHK cells in the presence of IFN-gamma and that TPA augments the process through the activation of protein kinase C.
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PMID:Interferon-gamma-dependent induction of manganese superoxide dismutase activity of SV40-transformed human keratinocytes by anti-Fas antibody and by TNF-alpha. 965 16