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
Archives of Biochemistry and Biophysics