Induction of nonmuscle myosin heavy chain II-C by butyrate in RAW 264.7 mouse macrophages.
RAW 264.7 macrophages express nonmuscle myosin heavy chain II-A as the only significant nonmuscle myosin heavy chain isoform, with expression of nonmuscle myosin heavy chain II-B and II-C low or absent. Treatment of the cells with sodium butyrate, an inhibitor of histone deacetylase, led to the dose-dependent induction of nonmuscle myosin heavy chain II-C. Trichostatin A, another inhibitor of histone deacetylase, also induced nonmuscle myosin heavy chain II-C. Induction of nonmuscle myosin heavy chain II-C in response to these histone deacetylase inhibitors was attenuated by mithramycin, an inhibitor of Sp1 binding to GC-rich DNA sequences. Bacterial lipopolysaccharide alone had no effect on basal nonmuscle myosin heavy chain II-C expression, but attenuated butyrate-mediated induction of nonmuscle myosin heavy chain II-C. The effects of lipopolysaccharide were mimicked by the nitric oxide donors sodium nitroprusside and spermine NONOate, suggesting a role for nitric oxide in the lipopolysaccharide-mediated down-regulation of nonmuscle myosin heavy chain II-C induction. This was supported by experiments with the inducible nitric-oxide synthase inhibitor 1400W, which partially blocked the lipopolysaccharide-mediated attenuation of nonmuscle myosin heavy chain induction. 8-Bromo-cGMP had no effect on nonmuscle myosin heavy chain induction, consistent with a cGMP-independent mechanism for nitric oxide-mediated inhibition of nonmuscle myosin heavy chain II-C induction.
Buxton
Denis B
DB
Laboratory of Molecular Cardiology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA. db225a@nih.gov
Golomb
Eliahu
E
Adelstein
Robert S
RS
D000123:Acetyltransferases / Q000037:antagonists & inhibitors; D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D002460:Cell Line; D006152:Cyclic GMP / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D051548:Histone Acetyltransferases; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018995:Myosin Heavy Chains / Q000096:biosynthesis*; D024462:Myosin Type II / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D020033:Protein Isoforms / Q000096:biosynthesis; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors; D016329:Sp1 Transcription Factor / Q000378:metabolism
D000123:Acetyltransferases; D002087:Butyrates; D006152:Cyclic GMP; D051548:Histone Acetyltransferases; D008070:Lipopolysaccharides; D018995:Myosin Heavy Chains; D024462:Myosin Type II; D009569:Nitric Oxide; D020030:Nitric Oxide Donors; D020033:Protein Isoforms; D029701:Saccharomyces cerevisiae Proteins; D016329:Sp1 Transcription Factor; C477830:MYH7b protein, human