NIOSHTIC-2 Publications Search
Calpain contributes to silica-induced IkB-a degradation and nuclear factor-kB activation.
Chen-F; Lu-Y; Kuhn-DC; Maki-M; Shi-X; Sun-SC; Demers-LM
Arch Biochem Biophys 1997 Jun; 342(2):383-388
Both silica and lipopolysaccharide (LPS) induce a rapid degradation of IkB-a, an intracellular inhibitor of the nuclear factor (NF)-kB transcription factor. In this report, we demonstrate that MG132, a relatively specific proteasome inhibitor, is capable of suppressing LPS-induced IkB-a degradation and NF-kB 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 IkB-a degradation induced by either silica or LPS. In fact, chloroquine enhances the signal-induced nuclear expression of NF-kB p50/p65 heterodimer by inhibiting the resynthesis of IkB-a. With the use of transient transfection of a plasmid that expresses calpastatin, a natural inhibitor for calpain, the silica-induced degradation of IkB-a and NF-kB activation was attenuated. In contrast, no inhibition of LPS-induced IkB-a degradation and NF-kB activation was observed by the overexpression of calpastatin. This suggests that calpain contributes to silica-induced IkB-a degradation and NF-kB activation but not to LPS-induced IkB-adegradation and NF-kB activation.
Genetic-factors; Genotoxic-effects; Cell-damage; Cellular-reactions; Quartz-dust; Silica-dusts
F. Chen, Department of Pathology, The Pennsylvania State University Collage of Medicine, The Milton S. Hershey Medical Center, P.O. Box 850, Hershey, Pennsylvania, 17033
Issue of Publication
Archives of Biochemistry and Biophysics