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Oxid Med Cell Longev. 2016;2016:9591482. doi: 10.1155/2016/9591482. Epub 2016 Dec 12.

CLOCK Promotes Endothelial Damage by Inducing Autophagy through Reactive Oxygen Species.

Author information

1
Institute of Vascular Surgery, Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
2
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
3
Department of Vascular Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Abstract

A number of recent studies have implicated that autophagy was activated by reactive oxygen species (ROS). Our previous report indicated that CLOCK increased the accumulation of ROS under hypoxic conditions. In this study, we investigated the mechanisms by which CLOCK mediated endothelial damage, focusing on the involvement of oxidative damage and autophagy. Overexpression of CLOCK in human umbilical vein endothelial cells (HUVECs) showed inhibition of cell proliferation and higher autophagosome with an increased expression of Beclin1 and LC3-I/II under hypoxic conditions. In contrast, CLOCK silencing reversed these effects. Interestingly, pretreatment with 3-methyladenine (3-MA) resulted in the attenuation of CLOCK-induced cell autophagy and but did not influence the production of intracellular reactive oxygen species (ROS). Furthermore, Tiron (4,5-dihydroxy-1,3-benzene disulfonic acid-disodium salt), a ROS scavenger, significantly attenuated CLOCK-induced cell autophagy. In addition, we found that overexpression of CLOCK had no significant effects on the production of ROS and expression of Beclin1 and LC3-I/II under normoxic conditions in HUVEC. In this present investigation, our results suggested a novel mechanism of action of CLOCK in HUVECs, opening up the possibility of targeting CLOCK for the treatment of vascular diseases.

PMID:
28058089
PMCID:
PMC5183792
DOI:
10.1155/2016/9591482
[Indexed for MEDLINE]
Free PMC Article

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