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Involvement of Kv1.5 protein in oxidative vascular endothelial cell injury.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (11), pp. e49758. Date of Electronic Publication: 2012 Nov 21. - Publication Year :
- 2012
-
Abstract
- Endothelial injury related to oxidative stress is a key event in cardiovascular diseases, such as hypertension and atherosclerosis. The activation of the redox-sensitive Kv1.5 potassium channel mediates mitochondrial reactive oxygen species (ROS)-induced apoptosis in vascular smooth muscle cells and some cancer cells. Kv1.5 channel is therefore taken as a new potential therapeutic target for pulmonary hypertension and cancers. Although Kv1.5 is abundantly expressed in vascular endothelium, there is little knowledge of its role in endothelial injury related to oxidative stress. We found that DPO-1, a specific inhibitor of Kv1.5, attenuated H(2)O(2)-evoked endothelial cell apoptosis in an in vivo rat carotid arterial model. In human umbilical vein endothelial cells (HUVECs) and human pulmonary arterial endothelial cells (HPAECs), angiotensin II and oxLDL time- or concentration-dependently enhanced Kv1.5 protein expression in parallel with the production of intracellular ROS and endothelial cell injury. Moreover, siRNA-mediated knockdown of Kv1.5 attenuated, whereas adenovirus-mediated Kv1.5 cDNA overexpression enhanced oxLDL-induced cellular damage, NADPH oxidase and mitochondria-derived ROS production and restored the decrease in protein expression of mitochondria uncoupling protein 2 (UCP2). Collectively, these data suggest that Kv1.5 may play an important role in oxidative vascular endothelial injury.
- Subjects :
- Adenoviridae genetics
Adenoviridae metabolism
Animals
Carotid Arteries pathology
Human Umbilical Vein Endothelial Cells
Humans
Hydrogen Peroxide chemistry
Ion Channels metabolism
Lipoproteins, LDL metabolism
Male
Mitochondrial Proteins metabolism
Oxidative Stress
RNA, Small Interfering metabolism
Rats
Rats, Wistar
Reactive Oxygen Species
Uncoupling Protein 2
Apoptosis
Endothelial Cells cytology
Kv1.5 Potassium Channel metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23185428
- Full Text :
- https://doi.org/10.1371/journal.pone.0049758