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XPO1-mediated nuclear export of RNF146 protects from angiotensin II-induced endothelial cellular injury
- Source :
- Biochemical and biophysical research communications. 503(3)
- Publication Year :
- 2018
-
Abstract
- Endothelial cells death induced by angiotensin II (Ang II) plays a role in vascular injury. RNF146 is identified as a E3 ubiquitin ligase, which promotes cell survival under many types of stresses. However, the role of RNF146 in endothelial cellular injury is unknown. In human umbilical vein endothelial cells (HUVECs), Ang II treatment led to cell death by oxidative stress and promoted RNF146 to accumulate in nucleus in time dependent manner. Nuclear export signal was found in the RNF146's sequence. The interaction between RNF146 and XPO1 was further confirmed by co-immunoprecipitation. Inhibition of XPO1 with KPT-185 increased the level of RNF146 in nucleus. The expression of XPO1 was suppressed responding to Ang II treatment. Overexpression of XPO1 facilitated the nuclear shuttling of RNF146, which protected from Ang II-induced cell death. Moreover, overexpression of RNF146 in HUVECs reduced the cell death induced by Ang II, whereas inhibition of XPO1 abolished the protective effect of RNF146. Therefore, our data demonstrated that RNF146 was a protective factor against cell death induced by AngII in human endothelial cells, which was dependent on XPO1-mediated nuclear export.
- Subjects :
- 0301 basic medicine
Programmed cell death
Ubiquitin-Protein Ligases
Biophysics
Receptors, Cytoplasmic and Nuclear
Karyopherins
medicine.disease_cause
Biochemistry
Umbilical vein
03 medical and health sciences
XPO1
medicine
Human Umbilical Vein Endothelial Cells
Humans
Nuclear export signal
Molecular Biology
Cells, Cultured
Cell Nucleus
biology
L-Lactate Dehydrogenase
Chemistry
Angiotensin II
Cell Biology
Triazoles
Ubiquitin ligase
Cell biology
Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
Acrylates
cardiovascular system
biology.protein
Reactive Oxygen Species
Nucleus
Oxidative stress
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 503
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....a85a493ccc181e23663fae9fd8ee96c1