Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholesterol oxidation products, oxysterols, are thought to play a part in the initiation and development of human atherosclerotic lesions. Excessive body iron has been suggested to promote atherosclerosis and coronary heart disease through its pro-oxidative properties. In the present study, the associations between serum ferritin and plasma oxysterol concentrations were examined in 669 eastern Finnish men. Serum ferritin concentration had statistically significant (p <.05) direct correlations with most of the measured oxysterols. In multivariate adjusted regression models, serum ferritin concentration predicted significantly the levels of 27-hydroxycholesterol (beta = 0.13, p <.001), 7alpha-hydroxycholesterol (beta = 0.11, p =.005), 25-hydroxycholesterol (beta = 0.10, p =.007), 7-ketocholesterol (beta = 0.10, p =.009), and 7beta-hydroxycholesterol (beta = 0.10, p =.02). In conclusion, excess body iron, as assessed by serum ferritin, is associated with increased levels of circulating oxysterols, both of enzymatic and nonenzymatic origin, in man.
 ...
PMID:Serum ferritin concentration is associated with plasma levels of cholesterol oxidation products in man. 1455 56

Human atherosclerotic lesions typically contain large amounts of ferritin associated with apoptotic macrophages and foam cells, although the reasons are unknown. In the present investigation, we studied the relationship between ferritin induction and occurrence of apoptosis in 7beta-hydroxycholesterol (7beta-OH)-treated monocytic cells and macrophages. We found that 7beta-OH enlarges the intracellular labile iron pool, increases formation of reactive oxygen species (ROS), and induces ferritin and cytosolic accumulation of lipid droplets, lysosomal destabilization, and apoptototic macrophage death. Since ferritin is a phase II-type protective protein, our findings suggest that ferritin upregulation here worked as an inefficient defense mechanism. Addition to the culture medium of both a membrane-permeable iron chelator 10-phenanthroline and the non-membrane-permeable iron chelators apoferritin and desferrioxamine afforded significant protection against the 7beta-OH-induced effects. Consequently, endocytosed iron compounds dramatically augmented 7beta-OH-induced cytotoxicity. We conclude that oxidized lipid 7beta-OH causes not only foam cell formation but also oxidative damage with abnormal metabolism of cellular iron. The findings suggest that modulation of iron metabolism in human atheroma may be a potential therapeutic strategy against atherosclerosis.
 ...
PMID:Foam cell death induced by 7beta-hydroxycholesterol is mediated by labile iron-driven oxidative injury: mechanisms underlying induction of ferritin in human atheroma. 1614 Feb 7