Expression of heme oxygenase-1 protects endothelial cells from irradiation-induced apoptosis.
A common side effect of therapeutic use of ionizing irradiation is endothelial cell damage resulting in a variety of clinical complications. Thus, preservation of endothelial function after irradiation could potentially limit toxicity. Using the murine endothelioma cell line bEnd2 we show here that induction of heme oxygenase-1 (HO-1) by cobalt protoporphyrine IX (CoPP) inhibits irradiation-induced apoptosis. In contrast, HO-1 induction by tin protoporphyrine IX (SnPP), a HO-1 inhibitor, does not affect survival after irradiation. The protective effects of CoPP could be partially reversed by blockade of HO-1 function with SnPP after induction by CoPP. Vice versa, blockade of HO-1 function by SnPP was reversible using CoPP. Treatment with CoPP inhibited cytochrome c release induced by irradiation. These results demonstrate that HO-1 induction and activation prior to irradiation inhibits endothelial apoptosis and might be used for possible cell protection in vivo.
Ewing
P
P
Department of Hematology/Oncology, University of Regensburg, Regensburg, Germany.
Wilke
A
A
Eissner
G
G
Holler
E
E
Andreesen
R
R
Gerbitz
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D011878:Radiotherapy / Q000009:adverse effects; D014965:X-Rays
D008665:Metalloporphyrins; D045304:Cytochromes c; D051547:Heme Oxygenase-1