Impairment of NF-κB activation and modulation of gene expression by calpastatin

Fei Chen, Laurence M. Demers, Val Vallyathan, Yongju Lu, Vincent Castranova, Xianglin Shi

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

To address the involvement of the calpain system in both basal and silica-induced nuclear factor (NF)-κB activation, several human bronchial epithelial cell lines were established in which an intracellular inhibitor of calpain, calpastatin, was stably expressed. Reduced basal and silica-induced inhibitor (IκBα) degradation and NF-κB activation were observed in cells stably overexpressing calpastatin. In addition, the cells in which calpain was constitutively inhibited by the overexpression of calpastatin exhibited a notable morphological change. Whereas empty vector-transfected cells displayed a morphology indistinguishable from that of parental cells, cells overexpressing calpastatin exhibited a mosaic morphological change with reduced formation of lamella 30 min after the cells were seeded. Genefilter microarray experiments, in which 3,965 human genes can be evaluated for their expression at the same time, showed that calpastatin downregulated genes encoding several membrane-associated proteins or nuclear proteins and upregulated genes of collagen α2, DAZ, and mitochondrial capsule selenoprotein. These results suggest that, in addition to their proteolytic activities on cytoskeletal proteins and other cellular regulatory proteins, calpain-calpastatin systems can also affect the expression levels of genes encoding structural or regulatory proteins.

Original languageEnglish (US)
Pages (from-to)C709-C716
JournalAmerican Journal of Physiology - Cell Physiology
Volume279
Issue number3 48-3
StatePublished - Oct 5 2000

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Gene Expression
Calpain
Silicon Dioxide
Selenoproteins
Genes
Cytoskeletal Proteins
Nuclear Proteins
Capsules
calpastatin
Membrane Proteins
Proteins
Collagen
Down-Regulation
Epithelial Cells
Cell Line

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

Cite this

Chen, F., Demers, L. M., Vallyathan, V., Lu, Y., Castranova, V., & Shi, X. (2000). Impairment of NF-κB activation and modulation of gene expression by calpastatin. American Journal of Physiology - Cell Physiology, 279(3 48-3), C709-C716.
Chen, Fei ; Demers, Laurence M. ; Vallyathan, Val ; Lu, Yongju ; Castranova, Vincent ; Shi, Xianglin. / Impairment of NF-κB activation and modulation of gene expression by calpastatin. In: American Journal of Physiology - Cell Physiology. 2000 ; Vol. 279, No. 3 48-3. pp. C709-C716.
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Chen, F, Demers, LM, Vallyathan, V, Lu, Y, Castranova, V & Shi, X 2000, 'Impairment of NF-κB activation and modulation of gene expression by calpastatin', American Journal of Physiology - Cell Physiology, vol. 279, no. 3 48-3, pp. C709-C716.

Impairment of NF-κB activation and modulation of gene expression by calpastatin. / Chen, Fei; Demers, Laurence M.; Vallyathan, Val; Lu, Yongju; Castranova, Vincent; Shi, Xianglin.

In: American Journal of Physiology - Cell Physiology, Vol. 279, No. 3 48-3, 05.10.2000, p. C709-C716.

Research output: Contribution to journalArticle

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Chen F, Demers LM, Vallyathan V, Lu Y, Castranova V, Shi X. Impairment of NF-κB activation and modulation of gene expression by calpastatin. American Journal of Physiology - Cell Physiology. 2000 Oct 5;279(3 48-3):C709-C716.