Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various cholesterol oxides generated during the oxidation of low-density lipoproteins have been reported to exert cytotoxic effects on cultured endothelial cells and to decrease their barrier function. The cytoskeleton, and in particular the actin microfilament meshwork, is one of the preferential targets in oxidative stress-and thiol-depleting agent-induced cell injury. The alterations occurring in the microfilament network were investigated using the endothelial cell line 73/73 treated with increasing concentrations (0.5-10 micrograms/ml) of cholestane-3 beta, 5 alpha, 6 beta-triol, CH, 5-cholesten-3beta-ol-7one, KC, and 25-OH-cholesterol, COH, for up to 6 h. The distribution of microfilaments was visualized using immunofluorescence and laser scanner confocal microscopy. All cholesterol oxides caused a progressive disruption of actin microfilaments that was characterized by the disappearance of the stress fibers within the cell body and, in selected cells, by a complete marginalization and clustering of the filaments to one edge of the cell. In addition, COH promoted F-actin fragmentation, as revealed by the presence of scattered fragments of F-actin in various cell regions. The redistribution of actin microfilaments was associated with a similar redistribution of alpha-actinin, an actin-binding protein involved in bundle formation and in the anchorage of actin filaments to the adhesion plaques. Concomitantly, cholesterol oxides promoted a loss of vinculin, another actin-binding protein, from the focal adhesion plaques located under the cell body and their marginalization and thinning. These alterations preceded cell detachment and cell death by apoptosis as revealed by the subsequent leakage of cytosolic enzymes and nuclear fragmentation. These results suggest that cytoskeletal (microfilament) alterations caused by cholesterol oxides may be one of the cytopathological events involved in the detachment of endothelial cells from the inner vascular surface promoted by cholesterol oxides.
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PMID:Disruption of actin microfilament organization by cholesterol oxides in 73/73 endothelial cells. 863 97

Rap small GTPases regulate excitatory synaptic strength and morphological plasticity of dendritic spines. Changes in spine structure are mediated by the F-actin cytoskeleton, but the link between Rap activity and actin dynamics is unclear. Here, we report a novel interaction between SPAR, a postsynaptic inhibitor of Rap, and alpha-actinin, a family of actin-cross-linking proteins. SPAR and alpha-actinin engage in bidirectional structural plasticity of dendritic spines: SPAR promotes spine head enlargement, whereas increased alpha-actinin2 expression favors dendritic spine elongation and thinning. Surprisingly, SPAR and alpha-actinin2 can function in an additive rather than antagonistic fashion at the same dendritic spine, generating combination spine/filopodia hybrids. These data identify a molecular pathway bridging the actin cytoskeleton and Rap at synapses, and suggest that formation of spines and filopodia are not necessarily opposing forms of structural plasticity.
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PMID:Combinatorial morphogenesis of dendritic spines and filopodia by SPAR and alpha-actinin2. 1939 16