Molecular mechanisms in peptidoglycan-induced human umbilical vascular endothelial cell apoptosis

Tsrang Neng Jang, Pei Ting Chiu, Wei Chuan Chen, Ming Jen Hsu

Research output: Contribution to journalArticle

Abstract

Peptidoglycan (PGN), a component of the outer membrane of Gram-positive bacteria has been implicated in the pathological process of sepsis. However, the molecular mechanism of PGN-induced vascular endothelium dysfunction has not been fully elucidated. Apoptosis signal regulating kinase 1 (ASK1) has been recently reported to play a crucial role in cell apoptosis under various cellular stresses. The purpose of this study was thus to investigate whether PGN-activated ASK1 results in cell apoptosis in human umbilical vascular endothelial cells (HUVECs). PGN was shown to cause a decrease in cell viability in a concentration-dependent manner. Flow cytometric analysis demonstrated that PGN increased the percentage of apoptotic cells. PGN induced ASK1 activation was accompanied by the increased phosphorylation of p38MAPK, a major downstream signaling molecule of ASK1. In addition, PGN was shown to increase apoptotic protein, Bax, expression in HUVECs. Inhibitor of p38MAPK signaling abrogated the PGN-increased DNA fragmentation and Bax expression, suggesting functional crosstalk. The toll-like receptor 2 (TLR2) agonist, Pam3CSK4, was also shown to induce ASK1 activation and p38MAPK phosphorylation, and subsequent cell apoptosis in HUVECs. Our data suggest that ASK1-p38MAPK cascade activation, followed by Bax expression, contributes to PGN-induced cell apoptosis.

Original languageEnglish
JournalJournal of Food and Drug Analysis
Volume19
Issue number2
Publication statusPublished - Jun 2011

Fingerprint

umbilicus
Umbilicus
Peptidoglycan
peptidoglycans
MAP Kinase Kinase Kinase 5
blood vessels
endothelial cells
apoptosis
Endothelial Cells
Apoptosis
phosphotransferases (kinases)
cells
phosphorylation
Phosphorylation
Toll-Like Receptor 2
bcl-2-Associated X Protein
Vascular Endothelium
Gram-Positive Bacteria
DNA Fragmentation
Pathologic Processes

Keywords

  • ASK1 (apoptosis signal regulating kinase 1)
  • Peptidoglycan (PGN)
  • Sepsis
  • Vascular leak syndromes

ASJC Scopus subject areas

  • Food Science
  • Pharmacology

Cite this

Molecular mechanisms in peptidoglycan-induced human umbilical vascular endothelial cell apoptosis. / Jang, Tsrang Neng; Chiu, Pei Ting; Chen, Wei Chuan; Hsu, Ming Jen.

In: Journal of Food and Drug Analysis, Vol. 19, No. 2, 06.2011.

Research output: Contribution to journalArticle

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