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Diesel exhaust particles induce human umbilical vein endothelial cells apoptosis by accumulation of autophagosomes and caspase-8 activation

Diesel exhaust particles (DEP) are risk factors for endothelial cells (ECs) dysfunction. However, the mechanism by which DEP induce ECs apoptosis remains unclear. Here, we investigated how DEP induce death of human umbilical vein ECs (HUVECs), with a focus on the autophagy-mediated apoptotic pathway...

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Autores principales: Kim, Geun-Young, Jung, Inkyo, Park, Minhan, Park, Kihong, Lee, Seung Hee, Kim, Won-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529885/
https://www.ncbi.nlm.nih.gov/pubmed/36192481
http://dx.doi.org/10.1038/s41598-022-21044-3
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author Kim, Geun-Young
Jung, Inkyo
Park, Minhan
Park, Kihong
Lee, Seung Hee
Kim, Won-Ho
author_facet Kim, Geun-Young
Jung, Inkyo
Park, Minhan
Park, Kihong
Lee, Seung Hee
Kim, Won-Ho
author_sort Kim, Geun-Young
collection PubMed
description Diesel exhaust particles (DEP) are risk factors for endothelial cells (ECs) dysfunction. However, the mechanism by which DEP induce ECs apoptosis remains unclear. Here, we investigated how DEP induce death of human umbilical vein ECs (HUVECs), with a focus on the autophagy-mediated apoptotic pathway. DEP induced dose-dependent HUVECs death and exposure to the IC(50) concentration of DEP (70 µg/ml) led to apoptosis. DEP phosphorylated Beclin-1 (Ser93) and increased protein levels of p62 and LC3BII and the number of LC3B puncta, indicating autophagy initiation. DEP increased expression of pro- and mature forms of cathepsin D, which increases lysosomal activity. However, DEP suppressed expression of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins (STX17, VAMP8, SNAP29, YKT6, and STX7) to inhibit autolysosome formation, resulting in accumulation of autophagosomes. LC3B, p62, and caspase-8 form a tertiary complex in accumulated autophagosomes, which is known to serve as a platform for caspase-8 activation. Indeed, DEP activates caspase-8 and pretreatment with a caspase-8 inhibitor suppressed DEP-induced apoptosis. Furthermore, depletion of p62 decreased caspase-8 and caspase-3 activation and inhibited the DEP-induced apoptosis. Taken together, these findings demonstrated that DEP induced HUVECs apoptosis by inhibiting autophagosome maturation and identified caspase-8 as a novel mediator of DEP-induced ECs apoptosis.
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spelling pubmed-95298852022-10-05 Diesel exhaust particles induce human umbilical vein endothelial cells apoptosis by accumulation of autophagosomes and caspase-8 activation Kim, Geun-Young Jung, Inkyo Park, Minhan Park, Kihong Lee, Seung Hee Kim, Won-Ho Sci Rep Article Diesel exhaust particles (DEP) are risk factors for endothelial cells (ECs) dysfunction. However, the mechanism by which DEP induce ECs apoptosis remains unclear. Here, we investigated how DEP induce death of human umbilical vein ECs (HUVECs), with a focus on the autophagy-mediated apoptotic pathway. DEP induced dose-dependent HUVECs death and exposure to the IC(50) concentration of DEP (70 µg/ml) led to apoptosis. DEP phosphorylated Beclin-1 (Ser93) and increased protein levels of p62 and LC3BII and the number of LC3B puncta, indicating autophagy initiation. DEP increased expression of pro- and mature forms of cathepsin D, which increases lysosomal activity. However, DEP suppressed expression of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins (STX17, VAMP8, SNAP29, YKT6, and STX7) to inhibit autolysosome formation, resulting in accumulation of autophagosomes. LC3B, p62, and caspase-8 form a tertiary complex in accumulated autophagosomes, which is known to serve as a platform for caspase-8 activation. Indeed, DEP activates caspase-8 and pretreatment with a caspase-8 inhibitor suppressed DEP-induced apoptosis. Furthermore, depletion of p62 decreased caspase-8 and caspase-3 activation and inhibited the DEP-induced apoptosis. Taken together, these findings demonstrated that DEP induced HUVECs apoptosis by inhibiting autophagosome maturation and identified caspase-8 as a novel mediator of DEP-induced ECs apoptosis. Nature Publishing Group UK 2022-10-03 /pmc/articles/PMC9529885/ /pubmed/36192481 http://dx.doi.org/10.1038/s41598-022-21044-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kim, Geun-Young
Jung, Inkyo
Park, Minhan
Park, Kihong
Lee, Seung Hee
Kim, Won-Ho
Diesel exhaust particles induce human umbilical vein endothelial cells apoptosis by accumulation of autophagosomes and caspase-8 activation
title Diesel exhaust particles induce human umbilical vein endothelial cells apoptosis by accumulation of autophagosomes and caspase-8 activation
title_full Diesel exhaust particles induce human umbilical vein endothelial cells apoptosis by accumulation of autophagosomes and caspase-8 activation
title_fullStr Diesel exhaust particles induce human umbilical vein endothelial cells apoptosis by accumulation of autophagosomes and caspase-8 activation
title_full_unstemmed Diesel exhaust particles induce human umbilical vein endothelial cells apoptosis by accumulation of autophagosomes and caspase-8 activation
title_short Diesel exhaust particles induce human umbilical vein endothelial cells apoptosis by accumulation of autophagosomes and caspase-8 activation
title_sort diesel exhaust particles induce human umbilical vein endothelial cells apoptosis by accumulation of autophagosomes and caspase-8 activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9529885/
https://www.ncbi.nlm.nih.gov/pubmed/36192481
http://dx.doi.org/10.1038/s41598-022-21044-3
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