Calpain contributes to silica-induced IκB-α degradation and nuclear factor-κB activation

Fei Chen, Yongju Lu, Douglas C. Kuhn, Masatoshi Maki, Xianglin Shi, Shao Cong Sun, Laurence M. Demers

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Both silica and lipopolysaccharide (LPS) induce a rapid degradation of IκBα, an intracellular inhibitor of the nuclear factor (NF)-κB transcription factor. In this report, we demonstrate that MG132, a relatively specific proteasome inhibitor, is capable of suppressing LPS-induced I≃Bα degradation and NF-≃B activation in mouse macrophage line RAW 264.7 cells, but is unable to influence the same induction produced by silica. In contrast, the lysosome inhibitor chloroquine has little effect on IκBα degradation induced by either silica or LPS. In fact, chloroquine enhances the signal-induced nuclear expression of NF-κB p50/p65 heterodimer by inhibiting the resynthesis of IκBα. With the use of transient transfection of a plasmid that expresses calpastatin, a natural inhibitor for calpain, the silica-induced degradation of IκBα and NF-κB activation was attenuated. In contrast, no inhibition of LPS-induced IκBα degradation and NF-κB activation was observed by the overexpression of calpastatin. This suggests that calpain contributes to silica-induced IκBα degradation and NF-κB activation but not to LPS-induced IκBα degradation and NF-κB activation.

Original languageEnglish
Pages (from-to)383-388
Number of pages6
JournalArchives of Biochemistry and Biophysics
Issue number2
StatePublished - Jun 15 1997

Bibliographical note

Funding Information:
This study was partially supported by the United States Bureau of Mines, Generic Mineral Technology Center For Respirable Dust (Grant G1145242) to Laurence M. Demers and NIOSH Grant VLA 107 to Fei Chen.


  • Calpain
  • IκBα
  • NF-κB
  • Silica

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology


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