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|Alternatives Splicing im Intron 13 der humanen eNOS: ein potentieller Mechanismus für die Regulation der eNOS-Aktivität|
|Main title||Alternatives Splicing im Intron 13 der humanen eNOS: ein potentieller Mechanismus für die Regulation der eNOS-Aktivität|
|Title variations||Alternative splicing in intron 13 of the human eNOS gene: a potential mechanism for regulating eNOS activity|
Place of birth: Münster
|1. Referee||Prof. Dr. med. K. Stangl|
|Further Referee(s)||Prof. Dr. med. M. Endres
Prof. Dr. S. Dimmeler
|Keywords||alternative splicing, endothelium, nitric oxide, NO, nitric oxide synthase, eNOS|
|Classification (DDC)||610 Medical sciences; Medicine|
|Summary||NO, the product of endothelial NOS (eNOS), is a major regulator of vascular homeostasis and a critical factor in preventing cardiovascular diseases. Whereas for human iNOS and nNOS a number of different splice variants have been described, no such splice isoforms are known for eNOS so far.
This study describes three novel splice variants for human eNOS. These splice variants - termed eNOS13A, eNOS13B and eNOS13C - share the first 13 exons of human eNOS followed by novel overlapping exons containing intron 13 sequences. All three splice variants share the same polyadenylation signal followed by a poly-A tail.
When translated, these splice-variants would result in truncated eNOS proteins lacking eNOS activity. Coexpression of full-length and eNOS13A in COS-7 cells diminished eNOS enzyme activity by formation of heterodimers. Coexpression in COS-7 cells with inhibition of the proteasome suggest an enhanced degradation of the heterodimers by the ubiquitin-proteasome-system.
All three splice-variants were expressed in different endothelial cells and various human tissues. Expression of eNOS13A was particularly high in human testis.
Taken together, these data suggest a new mechanism for the regulation of eNOS activity and NO production by dominant-negative splice variants of human eNOS.
Dataobject from FUDISS_thesis_000000004248
|FU Department||Department of Medicine - Charité - University Medicine Berlin|
|Year of publication||2008|
|Document type||Doctoral thesis|
|Date of defense||2008-09-19|
|Created at||2008-07-15 : 08:50:07|
|Last changed||2010-02-19 : 02:45:22|