Modulation of endothelial cell apoptosis by heme oxygenase-1-derived carbon monoxide.
It is well established that expression of heme oxygenase-1 (HO-1) acts in a cytoprotective manner in a variety of cell types, including in endothelial cells (EC). We have recently shown that HO-1 expression protects EC from undergoing apoptosis. We have also shown that the antiapoptotic effect of HO-1 is mediated through heme catabolism into the gas carbon monoxide (CO). In this review, we discuss the possible molecular mechanisms by which HO-1-derived CO suppresses EC apoptosis. We will review data suggesting that the antiapoptotic effect of CO acts through the activation of the p38 mitogen-activated protein kinase signal transduction pathway and requires the activation of the transcription factor nuclear factor-kappa B (NF-kappa B), as well as the expression of a subset of NF-kappa B-dependent antiapoptotic genes.
Soares
Miguel P
MP
Immunobiology Research Center, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. msoares@caregroup.harvard.edu
Usheva
Anny
A
Brouard
Sophie
S
Berberat
Pascal O
PO
Gunther
Lukas
L
Tobiasch
Edda
E
Bach
Fritz H
FH
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002248:Carbon Monoxide / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D008565:Membrane Proteins; D015398:Signal Transduction / Q000502:physiology
D008565:Membrane Proteins; D002248:Carbon Monoxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1