Calpain contributes to silica-induced I kappa B-alpha degradation and nuclear factor-kappa B activation.
Both silica and lipopolysaccharide (LPS) induce a rapid degradation of I kappa B alpha, an intracellular inhibitor of the nuclear factor (NF)-kappa B transcription factor. In this report, we demonstrate that MG132, a relatively specific proteasome inhibitor, is capable of suppressing LPS-induced I kappa B alpha degradation and NF-kappa 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 I kappa B alpha degradation induced by either silica or LPS. In fact, chloroquine enhances the signal-induced nuclear expression of NF-kappa B p50/p65 heterodimer by inhibiting the resynthesis of I kappa B alpha. With the use of transient transfection of a plasmid that expresses calpastatin, a natural inhibitor for calpain, the silica-induced degradation of I kappa B alpha and NF-kappa B activation was attenuated. In contrast, no inhibition of LPS-induced I kappa B alpha degradation and NF-kappa B activation was observed by the overexpression of calpastatin. This suggests that calpain contributes to silica-induced I kappa B alpha degradation and NF-kappa B activation but not to LPS-induced I kappa B alpha degradation and NF-kappa B activation.
Chen
F
F
Department of Pathology, Pennsylvania State University Collage of Medicine, Milton S. Hershey Medical Center, Hershey 17033, USA. fxc7@email.psu.edu
Lu
Y
Y
Kuhn
D C
DC
Maki
M
M
Shi
X
X
Sun
S C
SC
Demers
L M
LM
D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D002154:Calpain / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002457:Cell Extracts / Q000737:chemistry; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020672:I-kappa B Proteins; D007976:Leupeptins / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D012822:Silicon Dioxide / Q000494:pharmacology*; D014162:Transfection
D002135:Calcium-Binding Proteins; D002457:Cell Extracts; D015853:Cysteine Proteinase Inhibitors; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007976:Leupeptins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D000072000:NF-KappaB Inhibitor alpha; D012822:Silicon Dioxide; C033668:calpastatin; D002738:Chloroquine; D002154:Calpain; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde