Daxx inhibits stress-induced apoptosis in cardiac myocytes.
The role of the death-associated protein Daxx in modulation of apoptosis induced in cardiac myocytes by oxidative stress was studied. Exposure of cultured cardiomyocyte-like cells to oxidative stress or simulated hypoxia increased the level of accumulated ROS and apoptosis. Under conditions of sub-apoptotic stimulation of cardiac myocytes, there was no increase in the level of the Daxx protein, but it translocated from the nucleus to the cytoplasm. Daxx overexpression protected the cells from apoptosis, while they were sensitised to cell death following its down-regulation by siRNA. Moreover, lowering the level of the Daxx protein sensitised cardiac myocytes to spontaneous apoptosis, suggesting that the protein may also have a pro-survival role under physiological conditions. Finally, it was shown that DJ-1, a protein suggested previously to sequester Daxx in the nucleus under conditions of oxidative stress (thereby preventing its cytosolic translocation), was localised solely in the cytoplasm of cardiac myocytes. This indicates that the protein does not modulate the apoptosis regulatory activity of Daxx in cardiac myocytes by its nuclear sequestration. Taken together, Daxx plays a protective role in cultured cardiomyocyte-like cells, at least under the conditions used.
Zobalova
Renata
R
Apoptosis Research Group, School of Medical Science, Griffith University and Griffith Institute of Health and Medical Research, Southport, Queensland, Australia.
Swettenham
Emma
E
Chladova
Jaromira
J
Dong
Lan-Feng
LF
Neuzil
Jiri
J
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D056970:Co-Repressor Proteins; D003593:Cytoplasm / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018832:Molecular Chaperones; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015513:Oncogene Proteins / Q000378:metabolism; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C491473:Daxx protein, mouse; C528558:Daxx protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D054464:Peroxiredoxins; C503466:PARK7 protein, mouse; C404267:PARK7 protein, rat; D000071617:Protein Deglycase DJ-1