Apoptotic effects of TGFbeta superfamily members in isolated adult rat cardiomyocytes
| dc.contributor.author | Anwar, Muhammad Maqsud | |
| dc.date.accessioned | 2023-03-16T20:01:36Z | |
| dc.date.available | 2006-05-31T13:38:49Z | |
| dc.date.available | 2023-03-16T20:01:36Z | |
| dc.date.issued | 2006 | |
| dc.identifier.isbn | 3-8359-5031-2 | |
| dc.identifier.uri | http://nbn-resolving.de/urn:nbn:de:hebis:26-opus-28555 | |
| dc.identifier.uri | https://jlupub.ub.uni-giessen.de//handle/jlupub/13656 | |
| dc.identifier.uri | http://dx.doi.org/10.22029/jlupub-13038 | |
| dc.description.abstract | Several TGFbeta family members are upregulated in the heart by increased work load after myocardial infarction. Therefore, their expressions correlate with cardiac apoptosis induction in vivo. I have now tested in this study, if TGFbeta superfamily members induce apoptosis in ventricular cardiomyocytes of rat. Cardiomyocytes were stimulated with TGFbeta, myostatin, BMP-2, activin A or GDF15. Apoptosis was determined by detection of chromatin condensation and DNA laddering. Apoptosis was induced by TGFbeta, myostatin, activin A and BMP-2. A classical signaling molecule of TGF beta family members is the transcription factor SMAD, which is able to interact with AP-1, a factor known to mediate apoptosis in cardiomyocytes after NO stimulation. In retardation assays I have now demonstrated that AP-1 and SMAD binding were activated by TGFbeta, myostatin, BMP-2 or activin A. Intracellular scavenging of SMAD or AP-1 binding activity by transformation of cardiomyocytes with SMAD-decoy oligos or AP-1 decoy oligos inhibited apoptosis induction by TGF beta, myostatin, BMP-2 or activin A.GDF15 stimulates SMAD binding activity similar to the other family members. But in contrast to them GDF15 showed anti-apoptotic effects. It inhibited apoptosis induction by TGFbeta. Conclusions: Most of the investigated TGFbeta-superfamily members activate the transcription factors AP-1 and SMAD and induce apoptosis in cardiomyocytes. For TGFbeta, myostatin, BMP-2 and activin-A SMAD/AP-1 is a common pathway for apoptosis induction in cardiomyocytes. GDF 15 has anti-apoptotic effects and inhibits TGF beta induced apoptosis. Therefore, further investigations on GDF15 signaling may have potential to discover now anti-apoptotic therapies in heart. | en |
| dc.language.iso | en | de_DE |
| dc.rights | In Copyright | * |
| dc.rights.uri | http://rightsstatements.org/page/InC/1.0/ | * |
| dc.subject.ddc | ddc:610 | de_DE |
| dc.title | Apoptotic effects of TGFbeta superfamily members in isolated adult rat cardiomyocytes | en |
| dc.type | doctoralThesis | de_DE |
| dcterms.dateAccepted | 2006-03-13 | |
| local.affiliation | FB 11 - Medizin | de_DE |
| thesis.level | thesis.doctoral | de_DE |
| local.opus.id | 2855 | |
| local.opus.institute | Institut für Physiologie | de_DE |
| local.opus.fachgebiet | Medizin | de_DE |
| local.source.freetext | Giessen : VVB Laufersweiler 2006 | de_DE |
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