Ischemia induces nuclear NOX2 expression in cardiomyocytes and subsequently activates apoptosis
(2006) In Apoptosis 11(6). p.913-921- Abstract
- 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... (More)
- 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. (Less)
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https://lup.lub.lu.se/record/1135402
- author
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- apoptosis, free radicals, ischemia, NADPH oxidase
- in
- Apoptosis
- volume
- 11
- issue
- 6
- pages
- 913 - 921
- publisher
- Springer
- external identifiers
-
- pmid:16544099
- scopus:33745045502
- ISSN
- 1360-8185
- DOI
- 10.1007/s10495-006-6304-7
- language
- English
- LU publication?
- no
- id
- a675bb56-843f-4d3f-a00c-7d9a8881c882 (old id 1135402)
- date added to LUP
- 2016-04-01 11:40:33
- date last changed
- 2022-01-26 08:33:47
@article{a675bb56-843f-4d3f-a00c-7d9a8881c882,
abstract = {{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.}},
author = {{Meischl, C and Krijnen, P A J and Sipkens, J A and Cillessen, S A G M and Munoz, I Gamez and Okroj, Marcin and Ramska, M and Muller, A and Visser, C A and Musters, R J P and Simonides, W S and Hack, C E and Roos, D and Niessen, H W M}},
issn = {{1360-8185}},
keywords = {{apoptosis; free radicals; ischemia; NADPH oxidase}},
language = {{eng}},
number = {{6}},
pages = {{913--921}},
publisher = {{Springer}},
series = {{Apoptosis}},
title = {{Ischemia induces nuclear NOX2 expression in cardiomyocytes and subsequently activates apoptosis}},
url = {{http://dx.doi.org/10.1007/s10495-006-6304-7}},
doi = {{10.1007/s10495-006-6304-7}},
volume = {{11}},
year = {{2006}},
}