Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.14 (ATP synthase)
 7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Numerous investigations point to the importance of oxidative imbalance in mediating AD pathogenesis. Accumulated evidence indicates that lipid peroxidation is an early event during the evolution of the disease and occurs in patients with mild cognitive impairment (MCI). Because MCI represents a condition of increased risk for Alzheimer's disease (AD), early detection of disease markers is under investigation. Previously we showed that HNE-modified proteins, markers of lipid peroxidation, are elevated in MCI hippocampus and inferior parietal lobule compared to controls. Using a redox proteomic approach, we now report the identity of 11 HNE-modified proteins that had significantly elevated HNE levels in MCI patients compared with controls that span both brain regions: Neuropolypeptide h3, carbonyl reductase (NADPH), alpha-enolase, lactate dehydrogenase B, phosphoglycerate kinase, heat shock protein 70, ATP synthase alpha chain, pyruvate kinase, actin, elongation factor Tu, and translation initiation factor alpha. The enzyme activities of lactate dehydrogenase, ATP synthase, and pyruvate kinase were decreased in MCI subjects compared with controls, suggesting a direct correlation between oxidative damage and impaired enzyme activity. We suggest that impairment of target proteins through the production of HNE adducts leads to protein dysfunction and eventually neuronal death, thus contributing to the biological events that may lead MCI patients to progress to AD.
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PMID:Redox proteomic identification of 4-hydroxy-2-nonenal-modified brain proteins in amnestic mild cognitive impairment: insight into the role of lipid peroxidation in the progression and pathogenesis of Alzheimer's disease. 1832 75

Er-Xian Decoction (EXD) has been used for the treatment of osteoporosis disorders, menopausal syndrome, and other aging diseases in the Chinese traditional healthcare system. However, the targets and mechanism of action have not been clarified. This study was designed to investigate the effects and possible target proteins of EXD on osteoblastic UMR-106 cells and osteoclasts induced from RAW264.7 cells using the proteomic analysis technique. We found that EXD at a concentration of 50-200 microg/mL significantly enhanced osteoblastic UMR-106 cell proliferation, alkaline phosphatase (ALP) activity and formation of bone nodules, and decreased tartrate-resistant acid phosphatase (TRAP) activity and the bone resorption action of osteoclasts induced from RAW 264.7 cells. In EXD-treated osteoblasts, there were increases in the expression of heat-shock protein 1, high mobility group protein (Hmgb1), acidic ribosomal phosphoprotein P0, histone 2, carbonyl reductase 1, ATP synthase, aldolase A, and Rho GDP dissociation inhibitor (GDI)-alpha; and reduction in the expression of carbonic anhydrase 3, prohibitin, hemiferrin, far upstream element (FUSE)-binding protein. In EXD-treated osteoclasts, there were increases in the expression of vimentin, protein disulfide isomerase associated 3 and alpha-fetoprotein; and reduction in the expression of calnexin. These results indicated that EXD modulates bone metabolism through regulation of osteoblastic proliferation, apoptosis, and cell activation, and osteoclastic protein folding and aggregation.
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PMID:Antiosteoporotic effects and proteomic characterization of the target and mechanism of an Er-Xian Decoction on osteoblastic UMR-106 and osteoclasts induced from RAW264.7. 2065 86