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| Content Provider | Springer Nature Link |
|---|---|
| Author | Huang, Qi Ren Li, Qing Chen, Yuan Hong Li, Li Liu, Li Li Lei, Shui Hong Chen, He Ping Peng, Wei Jie He, Ming |
| Copyright Year | 2010 |
| Abstract | Excess apoptosis of endothelial cells (EC) plays crucial roles in the onset and progression of vasculopathy in diabetes mellitus. Anion exchanger-2 (AE2) might be involved in the vasculopathy. However, little is known about the molecular mechanisms that AE2 mediated the apoptosis of EC. The purpose of this study was to explore the role of AE2 in the apoptosis of HUVECs induced by high glucose (HG) and its possible mechanisms. First, HUVECs were exposed to different glucose concentrations (5.5, 17.8, 35.6, 71.2 and 142.4 mmol/l, respectively, pH = 7.40) for different time points (12, 24, 48, 72, 120, and 168 h, respectively). Intracellular Cl− concentration ([Cl−]i), AE2 expression and the apoptosis were assayed. Then, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS), Cl−-free media or specific RNA interference (RNAi) for AE2 was used to confirm whether AE2 could mediate the apoptosis induced by HG. Finally, the mechanisms of the AE2-mediated apoptosis were investigated by detecting mitochondrial permeability transition pore (mPTP, ΔΨm) openings, reactive oxygen species (ROS) levels and Caspase-3 activity. We found that HG upregulated the AE2 expression and activity, increased [Cl−]i and induced the apoptosis in a time- and concentration-dependent manner. The apoptosis of HUVECs by HG was possibly mediated by AE2 through an mPTP-ROS-Caspase-3 dependent pathway. These findings suggested that AE2 was likely to be a glucose-sensitive transmembrane transporter and a novel potential therapeutic target for diabetic vasculopathy. |
| Starting Page | 693 |
| Ending Page | 704 |
| Page Count | 12 |
| File Format | |
| ISSN | 13608185 |
| Journal | Apoptosis |
| Volume Number | 15 |
| Issue Number | 6 |
| e-ISSN | 1573675X |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2010-02-24 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Anion exchanger-2 Apoptosis Caspase-3 Endothelial cells Mitochondrial permeability transition pore Reactive oxygen species Virology Biochemistry Oncology Cell Biology Cancer Research |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmaceutical Science Biochemistry (medical) Cell Biology Clinical Biochemistry Cancer Research Pharmacology |
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