Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One representative of a number of severe lesions that occur outside the glomerular capillaries and involve podocytes is crescentic glomerulonephritis. The question of whether the crescent-forming cells are derived from glomerular epithelial cells or monocytes/macrophages is highly controversial and has not yet been clarified. To investigate the pathophysiology of podocytes in crescentic glomerulonephritis, we attempted to establish methods for culturing cells confirmed to be derived from podocytes, focusing particularly on the relationship between podocytes and macrophages. Nonadherent cells of unknown origin that grew from normal rat isolated glomerular cultures increased in number, reaching a total of 3.5 x 10(5)/ml on Day 11. They showed several characteristics of macrophages, the expression of specific antigens and enzymes, morphology, and production of H2O2. They expressed Fx1A but lacked the expressions of Thy1.1 or factor VIII. A morphologic kinetic study on Days 3 to 11 of culture showed that the cells with foot processes on the glomerular basement membrane changed into macrophagic cells (MC) and migrated from the glomeruli. Immunofluorescence double staining indicated that the cells that migrated from the glomerular surface on Day 8 were both anti-podocalyxin- and ED-1-positive. Furthermore, immunoelectron microscopy revealed that the ED-1-positive cells were located on the glomerular basement membrane. Pretreatment with anti-macrophages and -Thy1.1 antibodies, both with complement, did not reduce the number of MC, whereas pretreatment with puromycin aminonucleoside predominantly reduced the number of MC. A predominant decrease in the number of glomerular macrophages by gamma-irradiation did not result in a reduction of the number of MC. MC derived from glomerular cultures of bone marrow chimeric rats expressed the la antigen originated from recipient, which indicates that MC is not derived from bone marrow cells. Macrophage colony-stimulating factor accelerated the speed of the change into MC, and granulocyte-macrophage colony-stimulating factor dramatically enhanced its degree with increase of cell number on Day 8. We concluded that podocytes change into MC in normal rat glomerular culture and that the change is enhanced by colony-stimulating factors. The results provide a completely new insight into the origin of crescent-forming cells.
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PMID:Macrophagic cells outgrowth from normal rat glomerular culture: possible metaplastic change from podocytes. 894 Dec 17

Parkinson's disease (PD) is characterized by the progressive degeneration of nigrostriatal dopaminergic neurons leading to motor deficits. The mechanisms underlying the preferential vulnerability of nigrostriatal dopaminergic neurons in PD remain poorly understood. Recent evidence supports a role for mitochondrial dysfunction and increased oxidative stress in PD pathogenesis. Genetic and pathological studies also point to alpha-synuclein as a critical factor in both familial and sporadic forms of the disease; alpha-synuclein pathology affects mitochondrial function but is widespread in PD brain, raising the question of its role in the greater vulnerability of nigrostriatal neurons in PD. We have examined mitochondrial function and oxidative damage in mice overexpressing human wild type alpha-synuclein broadly throughout the nervous system under the Thy1 promoter (Thy1-aSyn mice) between 4 and 8months of age. Similar levels of alpha-synuclein accumulation in mitochondria were detected in the ventral midbrain, striatum and cortex of Thy1-aSyn mice. However, analysis of mitochondrial respiration using Seahorse XF analyzer showed defects in mitochondrial respiratory complexes I, II, IV and V specifically in the midbrain, and IV and V in the striatum, of Thy1-aSyn mice compared to wild type littermates; mitochondrial complex I activity assay by ELISA confirmed a 40% inhibition specifically in the ventral midbrain. Mitochondrial dysfunction can contribute to oxidative stress and we observed a 40% increase in 4-hydroxynenal and 2-fold increase in malondialdehyde levels, indicative of a high level of lipid peroxidation, specifically in the ventral midbrain of Thy1-aSyn mice. The levels of peroxiredoxin 2, a neuronal antioxidant enzyme that is involved in removal of H2O2 and other toxic peroxides were decreased in the midbrain whereas its oxidized form increased 4-fold, suggesting that antioxidant defenses were compromised in this region. In contrast, peroxiredoxin 2 increased in the striatum and cortex, which may contribute to their protection in the presence of high levels of alpha-synuclein. Thus, in mice over-expressing alpha-synuclein, mitochondrial dysfunction occurred preferentially in nigrostriatal dopaminergic neurons many months before striatal dopamine loss occurs at 14months of age. This may contribute to a higher level of oxidative stress that overwhelms antioxidant defense in these neurons, leading to their increased vulnerability in PD.
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PMID:Region specific mitochondrial impairment in mice with widespread overexpression of alpha-synuclein. 2501 98