| ironjustice@aol.com 2005-09-24, 2:00 pm |
| Free Radic Biol Med. 2005 Oct 1;39(7):864-875. Links
Foam cell death induced by 7beta-hydroxycholesterol is mediated by
labile iron-driven oxidative injury: Mechanisms underlying induction of
ferritin in human atheroma.
Li W, Hellsten A, Xu LH, Zhuang DM, Jansson K, Brunk UT, Yuan XM.
Division of Experimental Pathology, Faculty of Health Sciences,
Linkoping University, Linkoping SE-581 85, Sweden.
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: 16140207 [PubMed - as supplied by publisher]
--------------------------------------------------------------------------------
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://jesuswasavegetarian.7h.com
Man Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore
DEAD PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking
|