Ischemia induces nuclear NOX2 expression in cardiomyocytes and subsequently activates apoptosis
Författare
Summary, in English
In previous work we have demonstrated increased expression of NOX2 in cardiomyocytes of infarcted human hearts. In the present manuscript we investigated the functional role of NOX2 in ischemically challenged H9c2 cells, a rat cardiomyoblast cell line, and adult rat cardiomyocytes. Expression of NOX2 in H9c2 cells was confirmed by RT-PCR. In Western-blot experiments, increased NOX2 expression was detected during ischemia, which was inhibited by transcription and translation inhibitors. Surprisingly, under ischemia, in addition to an increased cytosolic expression, NOX2 was localized mainly in the nucleus of apoptotic cardiomyocytes, where it colocalized with nitrotyrosine residues and activated caspase 3. Inhibition of reactive-oxygen-species generation with the flavoenzyme inhibitor diphenylene iodonium (DPI) and the NADPH-oxidase inhibitor apocynin led to a significantly decreased induction of apoptosis as assessed by quantification of caspase-3 activity and by TUNEL analysis. These results demonstrate that NOX2 is expressed in the nucleus of cardiomyocytes during apoptosis and that it likely participates in proapoptotic signaling. To the best of our knowledge, this is the first demonstration of nuclear NOX2 expression and its involvement in cardiomyocyte apoptosis.
Publiceringsår
2006
Språk
Engelska
Sidor
913-921
Publikation/Tidskrift/Serie
Apoptosis
Volym
11
Issue
6
Dokumenttyp
Artikel i tidskrift
Förlag
Springer
Ämne
- Medicinal Chemistry
Nyckelord
- apoptosis
- free radicals
- ischemia
- NADPH oxidase
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1360-8185