Heme oxygenase-1-derived carbon monoxide stimulates adenosine triphosphate generation in human hepatocyte.
Heme oxygenases cleave the pro-oxidant heme molecule into carbon monoxide, ferrous iron, and biliverdin, which is subsequently converted to bilirubin. Increasing the enzymatic activities of heme oxygenase by expression of its inducible isoform, heme oxygenase-1, protects hepatocyte from apoptosis. In the present study, we investigated the mechanisms involving in heme oxygenase-1-mediated cytoprotection. Heme oxygenase-1 could induce the expression of anti-apoptotic protein-Bcl-xL in human hepatocyte. This effect is associated with the activation of p38 MAPK signaling pathway. Carbon monoxide derived from heme oxygenase activities significantly increased adenosine triphosphate levels in hepatocyte that was essential for potentiation of the activation of p38 MAPK signaling. Our demonstration of the importance of the energy status to maximize an anti-apoptotic response provides a new insight into HO-mediated cytoprotection.
Tsui
Tung-Yu
TY
Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong, China. tung-yu.tsui@klinik.uni-regensburg.de
Siu
Yeung-Tung
YT
Schlitt
Hans J
HJ
Fan
Sheung-Tat
ST
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D002248:Carbon Monoxide / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051020:bcl-X Protein; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C494811:BCL2L1 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D002248:Carbon Monoxide; D000255:Adenosine Triphosphate; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases