Reactive oxygen species and caspase activation mediate silica-induced apoptosis in alveolar macrophages

Han Ming Shen, Zhuo Zhang, Qi Feng Zhang, Choon Nam Ong

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Alveolar macrophages (AMs) are the principal target cells of silica and occupy a key position in the pathogenesis of silica-related diseases. Silica has been found to induce apoptosis in AMs, whereas its underlying mechanisms involving the initiation and execution of apoptosis are largely unknown. The main objective of the present study was to examine the form of cell death caused by silica and the mechanisms involved. Silica-induced apoptosis in AMs was evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay and cell cycle/DNA content analysis. The elevated level of reactive oxygen species (ROS), caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage in silica-treated AMs were also determined. The results showed that there was a temporal pattern of apoptotic events in silica-treated AMs, starting with ROS formation and followed by caspase-9 and caspase-3 activation, PARP cleavage, and DNA fragmentation. Silica-induced apoptosis was significantly attenuated by a caspase-3 inhibitor, N-acetyl-Asp-Glu-Val-Asp aldehyde, and ebselen, a potent antioxidant. These findings suggest that apoptosis is an important form of cell death caused by silica exposure in which the elevated ROS level that results from silica exposure may act as an initiator, leading to caspase activation and PARP cleavage to execute the apoptotic process.

Original languageEnglish
Pages (from-to)L10-L17
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1 24-1
StatePublished - Jan 2001


  • Antioxidants
  • Ebselen
  • Poly(adenosine 5′-diphosphate-ribose) polymerase
  • Terminal deoxynucleotidyltransferase-mediated deoxyuridine 5′-triphosphate nick end-labeling assay

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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