N-3-oxododecanoyl homoserine lactone exacerbates endothelial cell death by inducing receptor-interacting protein kinase 1-dependent apoptosis
- Authors
- Shin, Jungho; Ahn, Sun Hee; Kim, Su Hyun; Oh, Dong-Jin
- Issue Date
- Oct-2021
- Publisher
- AMER PHYSIOLOGICAL SOC
- Keywords
- endothelial cell; lipopolysaccharide; N-3-oxododecanoyl homoserine lactone; quorum-sensing molecule; receptor-interacting pro-tein kinase 1
- Citation
- AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, v.321, no.4, pp.C644 - C653
- Indexed
- SCIE
SCOPUS
- Journal Title
- AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
- Volume
- 321
- Number
- 4
- Start Page
- C644
- End Page
- C653
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/140805
- DOI
- 10.1152/ajpcell.00094.2021
- ISSN
- 0363-6143
- Abstract
- Endothelial dysfunction is associated with the initiation of sepsis-associated organ failure. Bacterial quorum-sensing molecules act as pathogen-associated molecular patterns; however, the effects of quorum-sensing molecules on endothelial cells remain less understood. This study investigated the molecular mechanisms of quorum-sensing molecule-induced cell death and their interaction with lipopolysaccharide (LPS) in human umbilical vein endothelial cells. Endothelial cells were treated with N-3-oxodo-decanoyl homoserine lactone (3OC12-HSL) and LPS derived from Pseudomonas aeruginosa. Treatment with 3OC12-HSL reduced cell viability in a dose-dependent manner, and cotreatment with 3OC12-HSL and LPS enhanced cell death. Terminal deoxynu-cleotidyl transferase deoxyuridine triphosphate nick end labeling assay revealed an increase in apoptotic cell death following 3OC12-HSL treatment; furthermore, cotreatment with 3OC12-HSL and LPS enhanced apoptosis. Western blotting revealed that treatment with 3OC12-HSL activated the receptor-interacting protein kinase 1 (RIPK1) pathway, leading to an increase in the levels of cleaved caspase 8 and 3. In addition, we found that treatment with necrostatin-1, an RIPK1 inhibitor, reduced cell death and ameliorated the activation of the RIPK1-dependent apoptotic pathway in 3OC12-HSL-treated cells. In conclusion, 3OC12-HSL induced endothelial cell apoptosis via the activation of the RIPK1 pathway, independent of LPS toxicity. Inhibition of RIPK1 may act as a therapeutic option for preserving endothelial cell integrity in patients with sepsis by disrupting the mechanism by which quorum-sensing molecules mediate their toxicity.
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