Cortactin Modulates Lung Endothelial Apoptosis Induced by Cigarette Smoke

Cigarette smoke (CS) is the primary cause of Chronic Obstructive Pulmonary Disease (COPD), and an important pathophysiologic event in COPD is CS-induced apoptosis in lung endothelial cells (EC). Cortactin (CTTN) is a cytoskeletal actin-binding regulatory protein with modulation by Src-mediated tyros...

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Autores principales:	Mounica Bandela, Eleftheria Letsiou, Viswanathan Natarajan, Lorraine B. Ware, Joe G. N. Garcia, Sunit Singla, Steven M. Dudek
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	COPD lung injury e-cigarette mitochondrial ROS endothelium cytoskeleton Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/55d0f7a9b8eb4445a04a583c171cf7b5
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spelling	oai:doaj.org-article:55d0f7a9b8eb4445a04a583c171cf7b52021-11-25T17:08:18ZCortactin Modulates Lung Endothelial Apoptosis Induced by Cigarette Smoke10.3390/cells101128692073-4409https://doaj.org/article/55d0f7a9b8eb4445a04a583c171cf7b52021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2869https://doaj.org/toc/2073-4409Cigarette smoke (CS) is the primary cause of Chronic Obstructive Pulmonary Disease (COPD), and an important pathophysiologic event in COPD is CS-induced apoptosis in lung endothelial cells (EC). Cortactin (CTTN) is a cytoskeletal actin-binding regulatory protein with modulation by Src-mediated tyrosine phosphorylation. Based upon data demonstrating reduced <i>CTTN</i> mRNA levels in the lungs of smokers compared to non-smokers, we hypothesized a functional role for CTTN in CS-induced mitochondrial ROS generation and apoptosis in lung EC. Exposure of cultured human lung EC to CS condensate (CSC) led to the rearrangement of the actin cytoskeleton and increased CTTN tyrosine phosphorylation (within hours). Exposure to CS significantly increased EC mitochondrial ROS generation and EC apoptosis. The functional role of CTTN in these CSC-induced EC responses was explored using cortactin siRNA to reduce its expression, and by using a blocking peptide for the CTTN SH3 domain, which is critical to cytoskeletal interactions. CTTN siRNA or blockade of its SH3 domain resulted in significantly increased EC mitochondrial ROS and apoptosis and augmented CSC-induced effects. Exposure of lung EC to e-cigarette condensate demonstrated similar results, with CTTN siRNA or SH3 domain blocking peptide increasing lung EC apoptosis. These data demonstrate a novel role for CTTN in modulating lung EC apoptosis induced by CS or e-cigarettes potentially providing new insights into COPD pathogenesis.Mounica BandelaEleftheria LetsiouViswanathan NatarajanLorraine B. WareJoe G. N. GarciaSunit SinglaSteven M. DudekMDPI AGarticleCOPDlung injurye-cigarettemitochondrial ROSendotheliumcytoskeletonBiology (General)QH301-705.5ENCells, Vol 10, Iss 2869, p 2869 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COPD lung injury e-cigarette mitochondrial ROS endothelium cytoskeleton Biology (General) QH301-705.5
spellingShingle	COPD lung injury e-cigarette mitochondrial ROS endothelium cytoskeleton Biology (General) QH301-705.5 Mounica Bandela Eleftheria Letsiou Viswanathan Natarajan Lorraine B. Ware Joe G. N. Garcia Sunit Singla Steven M. Dudek Cortactin Modulates Lung Endothelial Apoptosis Induced by Cigarette Smoke
description	Cigarette smoke (CS) is the primary cause of Chronic Obstructive Pulmonary Disease (COPD), and an important pathophysiologic event in COPD is CS-induced apoptosis in lung endothelial cells (EC). Cortactin (CTTN) is a cytoskeletal actin-binding regulatory protein with modulation by Src-mediated tyrosine phosphorylation. Based upon data demonstrating reduced <i>CTTN</i> mRNA levels in the lungs of smokers compared to non-smokers, we hypothesized a functional role for CTTN in CS-induced mitochondrial ROS generation and apoptosis in lung EC. Exposure of cultured human lung EC to CS condensate (CSC) led to the rearrangement of the actin cytoskeleton and increased CTTN tyrosine phosphorylation (within hours). Exposure to CS significantly increased EC mitochondrial ROS generation and EC apoptosis. The functional role of CTTN in these CSC-induced EC responses was explored using cortactin siRNA to reduce its expression, and by using a blocking peptide for the CTTN SH3 domain, which is critical to cytoskeletal interactions. CTTN siRNA or blockade of its SH3 domain resulted in significantly increased EC mitochondrial ROS and apoptosis and augmented CSC-induced effects. Exposure of lung EC to e-cigarette condensate demonstrated similar results, with CTTN siRNA or SH3 domain blocking peptide increasing lung EC apoptosis. These data demonstrate a novel role for CTTN in modulating lung EC apoptosis induced by CS or e-cigarettes potentially providing new insights into COPD pathogenesis.
format	article
author	Mounica Bandela Eleftheria Letsiou Viswanathan Natarajan Lorraine B. Ware Joe G. N. Garcia Sunit Singla Steven M. Dudek
author_facet	Mounica Bandela Eleftheria Letsiou Viswanathan Natarajan Lorraine B. Ware Joe G. N. Garcia Sunit Singla Steven M. Dudek
author_sort	Mounica Bandela
title	Cortactin Modulates Lung Endothelial Apoptosis Induced by Cigarette Smoke
title_short	Cortactin Modulates Lung Endothelial Apoptosis Induced by Cigarette Smoke
title_full	Cortactin Modulates Lung Endothelial Apoptosis Induced by Cigarette Smoke
title_fullStr	Cortactin Modulates Lung Endothelial Apoptosis Induced by Cigarette Smoke
title_full_unstemmed	Cortactin Modulates Lung Endothelial Apoptosis Induced by Cigarette Smoke
title_sort	cortactin modulates lung endothelial apoptosis induced by cigarette smoke
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/55d0f7a9b8eb4445a04a583c171cf7b5
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_version_	1718412712615084032

Cortactin Modulates Lung Endothelial Apoptosis Induced by Cigarette Smoke

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