Rat liver ferritin selectively inhibits expression of alpha-smooth muscle actin in cultured rat lipocytes.
The role of ferritin in lipocyte activation is unknown. This study examined the effect of rat liver ferritin (RLF), human recombinant H-ferritin (HrHF), human recombinant L-ferritin (HrLF), apo-ferritin (apo-RLF), and hemin on lipocyte activation. Lipocytes were cultured on uncoated plastic and were incubated with these agents for 7 days, at concentrations ranging from 10(-14) to 10(-7) M (0.5 to 50 microM for hemin). Collagen/noncollagen protein production and lipocyte proliferation were determined by [3H]proline and [3H]thymidine incorporation, respectively, and the expression of alpha-smooth muscle actin (alpha-SMA) and desmin was determined by Western blot. RLF, at concentrations ranging from 10(-10) to 10(-7) M, decreased alpha-SMA expression by 65-88%. Apo-RLF, HrHF, and HrLF decreased alpha-SMA by 17-45% at 10(-7) and 10(-8) M. Hemin (10 or 50 microM) inhibited alpha-SMA by 37 and 54%, respectively. Desmin expression was not altered by ferritin or hemin. Collagen and noncollagen protein production were not altered by either RLF or apo-RLF. Lipocyte proliferation was decreased by 54, 32, and 40%, by 10(-7) M RLF, HrHF, and HrLF, respectively, whereas apo-RLF had no effect. Thus RLF inhibited lipocyte alpha-SMA expression, which may be due to an effect of sequestered iron, since neither apo-RLF, HrHF, nor HrLF had a potent effect on alpha-SMA expression and all are essentially iron-free. The inhibitory effect of iron-loaded RLF on alpha-SMA expression suggests that tissue ferritin does not initiate lipocyte activation in iron overload, but rather may have a suppressive action on this process.
Ramm
G A
GA
Department of Internal Medicine, Saint Louis University School of Medicine, Missouri 63110-0250, USA.
Britton
R S
RS
O'Neill
R
R
Kohn
H D
HD
Bacon
B R
BR
D000199:Actins / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003893:Desmin / Q000378:metabolism; D005293:Ferritins / Q000187:drug effects / Q000502:physiology*; D006427:Hemin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins
D000199:Actins; D003893:Desmin; D011994:Recombinant Proteins; D006427:Hemin; D005293:Ferritins