sGC and PKG are indispensable for the induced expression of the
γ-globin gene by Hb F-inducing agents. (A) Induced
expression of the γ-globin gene by hemin or butyrate is abolished by
an sGC inhibitor. Cells were treated with 1 μM LY83583 (sGC
inhibitor) for 12 h and then incubated with hemin or arginine
butyrate for 3 days. (Left) Northern blot. Lanes M,
molecular weight marker; lane 1, control; lane 2, 1 μM LY83583; lane
3, 20 μM hemin; lane 4, 1 μM LY83583 + 20 μM hemin; lane 5,
control; lane 6, 1 mM arginine butyrate; lane 7, 1 μM LY83583 + 1 mM
arginine butyrate. (Right) Comparison of mRNA levels.
*, P < 0.001. (B) A
selective PKG inhibitor inhibits the induction of γ-globin gene
expression by hemin or butyrate. Cells were treated with 8 μM KT5823
(PKG inhibitor) for 12 h and then incubated with hemin or butyrate
for 3 days. (Left) Northern blots. Lanes M, moecule
weight markers; lane 1, control; lane 2, 8 μM KT5823; lane 3, 20 μM
hemin; lane 4, 8 μM KT5823 + 20 μM hemin; lane 5, 1 mM arginine
butyrate; lane 6, 8 μM KT5823 + 1 mM arginine butyrate. *,
P < 0.001; **, P
< 0.05.