Differential regulation and expression of stress proteins and ferritin in human monocytes.
We investigated the regulation and expression of ferritin in human cells by exposing peripheral blood monocytes (PBM) to heat shock (HS), opsonized sheep red blood cells (RBC), and iron. Iron induced ferritin but had no effect on stress protein expression. HS did not induce ferritin, indicating that ferritin is not a heat shock protein (HSP), at least in human PBM. In contrast, erythrophagocytosis (EP), a model for oxidative stress and endogenous iron release, induced HSP, heme oxygenase (HO), and ferritin. During EP, the antioxidant flavonoid quercetin prevented the induction of ferritin and HO, while it had no effect on the induction of ferritin by iron. In contrast, the iron chelator o-phenanthroline prevented the induction of ferritin during both EP and iron exposure. Differential effects of the transcriptional inhibitor actinomycin D on the various stress proteins revealed transcriptional regulation of HSP and HO during EP, whereas the induction of ferritin was posttranscriptionally regulated. We propose that while ferritin is not an HSP, its induction during EP is mediated through the action of ROS and is promoted by the iron released from RBC. Induction of ferritin and the subsequent iron sequestration may protect PBM from oxidative injury by limiting the iron-catalysed free radical reactions during EP.
Bornman
L
L
Laboratoire de Physiologie Respiratoire, University Paris V, France.
Baladi
S
S
Richard
M J
MJ
Tyrrell
R M
RM
Polla
B S
BS
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005293:Ferritins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep
D002614:Chelating Agents; D006360:Heat-Shock Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D010618:Phenanthrolines; D012333:RNA, Messenger; D003609:Dactinomycin; D005293:Ferritins; D011794:Quercetin; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); C025205:1,10-phenanthroline