Ceramide path in human lung cell death

Chris Chan, Tzipora Goldkorn

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Lung epithelium plays a significant role in modulating the inflammatory response to lung injury. Airway epithelial cells are targeted by hydrogen peroxide (H2O2) and oxygen radicals, which are agents commonly produced during inflammatory processes. The mechanisms and molecular sites affected by H2O2 are largely unknown but may involve the induction of sphingomyelin (SM) hydrolysis to generate ceramide, which serves as a second messenger in initiating an apoptotic response. Here we show that exposure of human airway epithelial (HAE) cells to 50 to 100 μM H2O2 induces within 5 to 10 rain a greater than 2-fold activation of neutral sphingomyelinase activity with concomitant SM hydrolysis, ceramide generation, and apoptosis. On the other hand, activation of protein kinase C (PKC) by 12-O-tetradecanoylphorbol-13-acetate inhibits both H2O2-induced ceramide production and apoptosis. The apoptotic response could be restored by the addition of 25 μM cell-permeant C6-ceramide. These findings indicate that ceramide, the product of SM hydrolysis, plays an important role in H2O2-induced apoptosis in HAE cells, and that PKC counteracts ceramide-mediated apoptosis in these cells. We suggest that the mediation of epithelial cell apoptosis by ceramide and its inhibition by PKC constitute a central mechanism by which inflammatory processes are modulated in the epithelium of the lung.

Original languageEnglish (US)
Pages (from-to)460-468
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume22
Issue number4
StatePublished - 2000

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Ceramides
Cell death
Cell Death
Lung
Sphingomyelins
Apoptosis
Epithelial Cells
Protein Kinase C
Hydrolysis
Epithelium
Chemical activation
Sphingomyelin Phosphodiesterase
Rain
Lung Injury
Second Messenger Systems
Tetradecanoylphorbol Acetate
Hydrogen Peroxide
Reactive Oxygen Species
Acetates

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Ceramide path in human lung cell death. / Chan, Chris; Goldkorn, Tzipora.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 22, No. 4, 2000, p. 460-468.

Research output: Contribution to journalArticle

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