Effects of the Cdc2-like kinase-family and DNA topoisomerase I on the alternative splicing of eNOS in TNF-α-stimulated human endothelial cells
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Abstract
Nitric oxide (NO) is synthesized by endothelial nitric oxide synthase (eNOS) and plays an important role in vascular homeostasis and cardiovascular diseases. It has recently been shown that increased expression of alternatively spliced eNOS isoforms eNOS 13A, B and C and heterodimerization with ‘full-length’ eNOS is associated with a decreased eNOS activity. The regulatory pathways enabling this phenomenon are completely unknown. This study examined the effect of Cdc2-like kinases and DNA topoisomerase I on eNOS splicing in TNF-α-induced human umbilical vein endothelial cells (HUVECs). We found that inhibition of DNA topoisomerase I, but not Cdc2-like kinases, prevents the TNF-α-induced increase in eNOS isoform expression and NO reduction in HUVEC. Moreover, we show that the inhibition of DNA topoisomerase I or the Cdc2-like kinases differently modulates the phosphorylation of the serine/arginine-rich proteins SRp75 and SRp55. Our results demonstrate, for the first time, that DNA topoisomerase I but not Cdc2-like kinases serves as an important regulator of the differential eNOS isoform expression in endothelial cells, thereby modulating the TNF-α-induced eNOS activity switch.
©2008 by Walter de Gruyter Berlin New York
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- Generation of synthetic RNA-based thermosensors
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- Impaired synthesis of heme oxygenase-1 in Fanconi anemia cells can be rescued by transfection of Fanconi wild-type cDNA
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- Effects of the Cdc2-like kinase-family and DNA topoisomerase I on the alternative splicing of eNOS in TNF-α-stimulated human endothelial cells
- Proteolysis
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Articles in the same Issue
- Guest Editorial
- Highlight – Viruses and Signaling
- Highlight: Viruses and Signaling
- HIV-1 at the immunological and T-lymphocytic virological synapse
- Pursuing different ‘TRADDes’: TRADD signaling induced by TNF-receptor 1 and the Epstein-Barr virus oncoprotein LMP1
- RNA viruses and the mitogenic Raf/MEK/ERK signal transduction cascade
- Hepatitis C virus (HCV) employs multiple strategies to subvert the host innate antiviral response
- Sabotage of antiviral signaling and effectors by influenza viruses
- Influenza viruses and the NF-κB signaling pathway – towards a novel concept of antiviral therapy
- Genes and Nucleic Acids
- Specific inhibition of transcriptional activity of the constitutive androstane receptor (CAR) by the splicing factor SF3a3
- Generation of synthetic RNA-based thermosensors
- Molecular Medicine
- Impaired synthesis of heme oxygenase-1 in Fanconi anemia cells can be rescued by transfection of Fanconi wild-type cDNA
- Cell Biology and Signaling
- Effects of the Cdc2-like kinase-family and DNA topoisomerase I on the alternative splicing of eNOS in TNF-α-stimulated human endothelial cells
- Proteolysis
- Cytotoxic and peptidase inhibitory activities of selected non-hepatotoxic cyclic peptides from cyanobacteria
