Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duchenne muscular dystrophy muscles undergo increased oxidative stress and altered calcium homeostasis, which contribute to myofiber loss by trigging both necrosis and apoptosis. Here, we asked whether treatment with free radical scavengers could improve the dystrophic pattern of mdx muscles. Five-week-old mdx mice were treated for 2 weeks with alpha-lipoic acid/l-carnitine. This treatment decreased the plasmatic creatine kinase level, the antioxidant enzyme activity, and lipid peroxidation products in mdx diaphragm. Free radical scavengers also modulated the phosphorylation/activity of some component of the mitogen-activated protein kinase (MAPK) cascades: p38 MAPK, the extracellular signal-related kinase, and the Jun kinase. beta-Dystroglycan (beta-DG), a multifunctional adaptor or scaffold capable of interacting with components of the extracellular signal-related kinase-MAP kinase cascade, was also affected after treatment. In the mdx muscles, beta-DG (43 kd) was cleaved by matrix metalloproteinases into a 30-kd form (beta-DG30). We show that the proinflammatory protein nuclear factor-kappaB activator decreased after the treatment, leading to a significant reduction of matrix metalloproteinase activity in the mdx diaphragm. Our data highlight the implication of oxidative stress and cell signaling defects in dystrophin-deficient muscle via the MAP kinase cascade-beta-DG interaction and nuclear factor-kappaB-mediated inflammation process.
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PMID:Modulation of p38 mitogen-activated protein kinase cascade and metalloproteinase activity in diaphragm muscle in response to free radical scavenger administration in dystrophin-deficient Mdx mice. 1725 31

Hypertension is accompanied by increased levels of reactive oxygen species, which may contribute to progressive renal injury and dysfunction. Here we tested the hypothesis that sensitivity to exogenous hydrogen peroxide (H(2)O(2)) is enhanced in immortalized renal proximal tubular epithelial cells from spontaneously hypertensive rats (SHR) compared to normotensive control Wistar Kyoto rats (WKY). We found that SHR cells were more sensitive to H(2)O(2)-induced cell death than WKY cells. Lower survival in SHR cells correlated with increased DNA fragmentation, chromatin condensation, and caspase-3 activity, indicating apoptosis. H(2)O(2) degradation was slower in SHR than in WKY cells, suggesting that reduced antioxidant enzyme activity might be the basis for their increased sensitivity. In fact, catalase activity was downregulated in SHR cells, whereas glutathione peroxidase activity was similar in both cell types. We next examined whether MAPK signaling pathways contributed to H(2)O(2)-mediated apoptosis. Inhibition of c-Jun NH(2)-terminal kinase (JNK) with SP600125 partially rescued H(2)O(2)-induced apoptosis in WKY but not in SHR cells. In addition, p54 JNK2 isoform was robustly phosphorylated by H(2)O(2), this effect being more pronounced in SHR cells. Together, these results suggest that the survival disadvantage of SHR cells upon exposure to H(2)O(2) stems from impaired antioxidant mechanisms and activated JNK proapoptotic signaling pathways.
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PMID:Loss of oxidative stress tolerance in hypertension is linked to reduced catalase activity and increased c-Jun NH2-terminal kinase activation. 2322 Feb 62