Activation of ATM-c-IAP1 Pathway Mediates the Protective Effects of Estradiol in Human Vascular Endothelial Cells Exposed to Intermittent Hypoxia

Ying Ni Lin,1,2,* Xiao Fei Lan,1,3,* Zhuo Ran Liu,4,* Ya Ru Yan,1,2 Jian Ping Zhou,1,2 Ning Li,1,2 Xian Wen Sun,1,2 Qing Yun Li1,2 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lin YN, Lan XF, Liu ZR, Yan YR, Zhou JP, Li N, Sun XW, Li QY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	estradiol obstructive sleep apnea (osa) intermittent hypoxia (ih) endothelial dysfunction proteomics Psychiatry RC435-571 Neurophysiology and neuropsychology QP351-495
Acceso en línea:	https://doaj.org/article/8245f6dc0bdc49e59128ec22c8c38b64
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8245f6dc0bdc49e59128ec22c8c38b64
record_format	dspace
spelling	oai:doaj.org-article:8245f6dc0bdc49e59128ec22c8c38b642021-12-02T07:03:21ZActivation of ATM-c-IAP1 Pathway Mediates the Protective Effects of Estradiol in Human Vascular Endothelial Cells Exposed to Intermittent Hypoxia1179-1608https://doaj.org/article/8245f6dc0bdc49e59128ec22c8c38b642019-11-01T00:00:00Zhttps://www.dovepress.com/activation-of-atm-c-iap1-pathway-mediates-the-protective-effects-of-es-peer-reviewed-article-NSShttps://doaj.org/toc/1179-1608Ying Ni Lin,1,2,* Xiao Fei Lan,1,3,* Zhuo Ran Liu,4,* Ya Ru Yan,1,2 Jian Ping Zhou,1,2 Ning Li,1,2 Xian Wen Sun,1,2 Qing Yun Li1,2 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China; 2Institute of Respiratory Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China; 3Department of Respiratory Medicine, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200335, People’s Republic of China; 4Department of Thyroid and Vascular Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing Yun LiDepartment of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of ChinaTel +86-21-64370045Email liqingyun68@hotmail.comPurpose: Chronic intermittent hypoxia (CIH) contributes to the increased risk of cardiovascular diseases in obstructive sleep apnea (OSA). We previously reported the anti-apoptotic effects of estradiol (E2) on IH-exposed human umbilical vein endothelial cells (HUVECs). Herein, we employed a proteomic analysis to elucidate the mechanisms of the protective effects of E2 under IH exposure.Methods: HUVECs were divided into three groups: control, IH, and IH+E2 group. Isobaric tags for relative and absolute quantification (iTRAQ) were performed to compare protein profiles among the groups. Some of the identified proteins were validated by Western blotting.Results: A total of 185 proteins were differentially expressed in the IH+E2 group compared to the IH group. Bioinformatics analysis indicated that the effects of E2 may be linked to the regulation of cellular stress response. Among the differentially expressed proteins, we identified that serine-protein kinase ataxia telangiectasia mutated (ATM) and its downstream target, cellular inhibitor of apoptosis protein 1 (c-IAP1), were up-regulated by E2. We also observed that E2 decreased the level of cleaved caspase-3 and inhibited cell apoptosis in IH-exposed HUVECs. The inhibition of ATM abolished the anti-apoptotic effect of E2.Conclusion: The ATM-c-IAP1 pathway is involved in the cardioprotective effects of E2 in HUVECs exposed to IH.Keywords: estradiol, obstructive sleep apnea, OSA, intermittent hypoxia, IH, endothelial dysfunction, proteomicsLin YNLan XFLiu ZRYan YRZhou JPLi NSun XWLi QYDove Medical Pressarticleestradiolobstructive sleep apnea (osa)intermittent hypoxia (ih)endothelial dysfunctionproteomicsPsychiatryRC435-571Neurophysiology and neuropsychologyQP351-495ENNature and Science of Sleep, Vol Volume 11, Pp 357-366 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	estradiol obstructive sleep apnea (osa) intermittent hypoxia (ih) endothelial dysfunction proteomics Psychiatry RC435-571 Neurophysiology and neuropsychology QP351-495
spellingShingle	estradiol obstructive sleep apnea (osa) intermittent hypoxia (ih) endothelial dysfunction proteomics Psychiatry RC435-571 Neurophysiology and neuropsychology QP351-495 Lin YN Lan XF Liu ZR Yan YR Zhou JP Li N Sun XW Li QY Activation of ATM-c-IAP1 Pathway Mediates the Protective Effects of Estradiol in Human Vascular Endothelial Cells Exposed to Intermittent Hypoxia
description	Ying Ni Lin,1,2,* Xiao Fei Lan,1,3,* Zhuo Ran Liu,4,* Ya Ru Yan,1,2 Jian Ping Zhou,1,2 Ning Li,1,2 Xian Wen Sun,1,2 Qing Yun Li1,2 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China; 2Institute of Respiratory Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China; 3Department of Respiratory Medicine, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200335, People’s Republic of China; 4Department of Thyroid and Vascular Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing Yun LiDepartment of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of ChinaTel +86-21-64370045Email liqingyun68@hotmail.comPurpose: Chronic intermittent hypoxia (CIH) contributes to the increased risk of cardiovascular diseases in obstructive sleep apnea (OSA). We previously reported the anti-apoptotic effects of estradiol (E2) on IH-exposed human umbilical vein endothelial cells (HUVECs). Herein, we employed a proteomic analysis to elucidate the mechanisms of the protective effects of E2 under IH exposure.Methods: HUVECs were divided into three groups: control, IH, and IH+E2 group. Isobaric tags for relative and absolute quantification (iTRAQ) were performed to compare protein profiles among the groups. Some of the identified proteins were validated by Western blotting.Results: A total of 185 proteins were differentially expressed in the IH+E2 group compared to the IH group. Bioinformatics analysis indicated that the effects of E2 may be linked to the regulation of cellular stress response. Among the differentially expressed proteins, we identified that serine-protein kinase ataxia telangiectasia mutated (ATM) and its downstream target, cellular inhibitor of apoptosis protein 1 (c-IAP1), were up-regulated by E2. We also observed that E2 decreased the level of cleaved caspase-3 and inhibited cell apoptosis in IH-exposed HUVECs. The inhibition of ATM abolished the anti-apoptotic effect of E2.Conclusion: The ATM-c-IAP1 pathway is involved in the cardioprotective effects of E2 in HUVECs exposed to IH.Keywords: estradiol, obstructive sleep apnea, OSA, intermittent hypoxia, IH, endothelial dysfunction, proteomics
format	article
author	Lin YN Lan XF Liu ZR Yan YR Zhou JP Li N Sun XW Li QY
author_facet	Lin YN Lan XF Liu ZR Yan YR Zhou JP Li N Sun XW Li QY
author_sort	Lin YN
title	Activation of ATM-c-IAP1 Pathway Mediates the Protective Effects of Estradiol in Human Vascular Endothelial Cells Exposed to Intermittent Hypoxia
title_short	Activation of ATM-c-IAP1 Pathway Mediates the Protective Effects of Estradiol in Human Vascular Endothelial Cells Exposed to Intermittent Hypoxia
title_full	Activation of ATM-c-IAP1 Pathway Mediates the Protective Effects of Estradiol in Human Vascular Endothelial Cells Exposed to Intermittent Hypoxia
title_fullStr	Activation of ATM-c-IAP1 Pathway Mediates the Protective Effects of Estradiol in Human Vascular Endothelial Cells Exposed to Intermittent Hypoxia
title_full_unstemmed	Activation of ATM-c-IAP1 Pathway Mediates the Protective Effects of Estradiol in Human Vascular Endothelial Cells Exposed to Intermittent Hypoxia
title_sort	activation of atm-c-iap1 pathway mediates the protective effects of estradiol in human vascular endothelial cells exposed to intermittent hypoxia
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/8245f6dc0bdc49e59128ec22c8c38b64
work_keys_str_mv	AT linyn activationofatmciap1pathwaymediatestheprotectiveeffectsofestradiolinhumanvascularendothelialcellsexposedtointermittenthypoxia AT lanxf activationofatmciap1pathwaymediatestheprotectiveeffectsofestradiolinhumanvascularendothelialcellsexposedtointermittenthypoxia AT liuzr activationofatmciap1pathwaymediatestheprotectiveeffectsofestradiolinhumanvascularendothelialcellsexposedtointermittenthypoxia AT yanyr activationofatmciap1pathwaymediatestheprotectiveeffectsofestradiolinhumanvascularendothelialcellsexposedtointermittenthypoxia AT zhoujp activationofatmciap1pathwaymediatestheprotectiveeffectsofestradiolinhumanvascularendothelialcellsexposedtointermittenthypoxia AT lin activationofatmciap1pathwaymediatestheprotectiveeffectsofestradiolinhumanvascularendothelialcellsexposedtointermittenthypoxia AT sunxw activationofatmciap1pathwaymediatestheprotectiveeffectsofestradiolinhumanvascularendothelialcellsexposedtointermittenthypoxia AT liqy activationofatmciap1pathwaymediatestheprotectiveeffectsofestradiolinhumanvascularendothelialcellsexposedtointermittenthypoxia
_version_	1718399644364439552

Activation of ATM-c-IAP1 Pathway Mediates the Protective Effects of Estradiol in Human Vascular Endothelial Cells Exposed to Intermittent Hypoxia

Ejemplares similares