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 exa mined the effect of rat liver ferritin (RLF), human recombinant H-ferr itin (HrHF), human recombinant L-ferritin (HrLF), apoferritin (apo-RLF ), and hemin on lipocyte activation. Lipocytes were cultured on uncoat ed plastic and were incubated with these agents for 7 days, at concent rations ranging from 10(-14) to 10(-7) M (0.5 to 50 mu M for hemin). C ollagen/noncollagen protein production and lipocyte proliferation were determined by [H-3]proline and [H-3]thymidine incorporation, respecti vely, 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%. Ap o-RLF, HrHF, and HrLF decreased alpha-SMA by 17-45% at 10(-7) and 10(- 8) M. Hemin (10 or 50 mu M) inhibited alpha-SMA by 37 and 54%, respect ively. Desmin expression was not altered by ferritin or hemin. Collage n 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 eff ect. Thus RLF inhibited lipocyte alpha-SMA expression, which may be du e to an effect of sequestered iron, since neither apo-RLF, HrHF, nor H rLF had a potent effect on alpha-SMA expression and all are essentiall y iron-free. The inhibitory effect of iron-loaded RLF on alpha-SMA exp ression suggests that tissue ferritin does not initiate lipocyte activ ation in iron overload, but rather may have a suppressive action on th is process.