Upregulation of DAPK contributes to homocysteine-induced endothelial apoptosis via the modulation of Bcl2/Bax and activation of caspase 3

Tian,Xin; Shi,Yongfeng; Liu,Ning; Yan,Youyou; Li,Tianyi; Hua,Peiyan; Liu,Bin

doi:10.3892/mmr.2016.5733

Upregulation of DAPK contributes to homocysteine-induced endothelial apoptosis via the modulation of Bcl2/Bax and activation of caspase 3

Authors:
- Xin Tian
- Yongfeng Shi
- Ning Liu
- Youyou Yan
- Tianyi Li
- Peiyan Hua
- Bin Liu
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Affiliations: Department of Cardiology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China, Department of Thoracic Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China
Published online on: September 12, 2016 https://doi.org/10.3892/mmr.2016.5733
Pages: 4173-4179
Copyright: © Tian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hyperhomocysteinemia is characterized by an abnormally high level of homocysteine (Hcy) in the blood and is associated with cardiovascular diseases such as atherosclerosis. Endothelial dysfunction may lead to the pro-atherogenic effects associated with hyperhomocysteinemia. Endothelial dysfunction induced by Hcy has been previously investigated; however, the underlying molecular mechanism remains to be fully elucidated. The present study investigated whether death-associated protein kinase (DAPK) is involved in Hcy‑induced apoptosis in human umbilical vein endothelial cells (HUVECs). It was determined that Hcy treatment upregulated the mRNA and protein expression levels of DAPK in HUVECs. Additionally, it was identified that the knockdown of DAPK using small interfering RNA may attenuate the Hcy-induced apoptosis and dissipation of mitochondrial membrane potential. DAPK inhibition may also reverse the effect of Hcy by the upregulation of B cell leukemia/lymphoma 2 (Bcl2) and poly ADP‑ribose polymerase, and the downregulation of Bcl2‑associated X protein (Bax) and of caspase 3. In conclusion, the present study demonstrated that DAPK contributed to the Hcy‑induced endothelial apoptosis via modulation of Bcl2/Bax expression levels and activation of caspase 3.

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