Proinsulin C-Peptide Stimulates a PKC/IκB/NF-κB Signaling Pathway to Activate COX-2 Gene Transcription in Swiss 3T3 Fibroblasts

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By this author: Kitazawa, Masashi ;&nbsp; Shibata, Yasutaka ;&nbsp; Hashimoto, Seiichi ;&nbsp; Ohizumi, Yasushi ;&nbsp; Yamakuni, Tohru

Authors: Kitazawa, Masashi; Shibata, Yasutaka; Hashimoto, Seiichi; Ohizumi, Yasushi; Yamakuni, Tohru

Source: The Journal of Biochemistry, Volume 139, Number 6, June 2006 , pp. 1083-1088(6)

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Abstract:

Proinsulin C-peptide causes multiple molecular and physiological effects, and improves renal and neuronal dysfunction in patients with diabetes. However, whether C-peptide controls the inhibitor κB (IκB)/NF-κB-dependent transcription of genes, including inflammatory genes is unknown. Here we showed that 1 nM C-peptide increased the expression of cyclooxygenase-2 (COX-2) mRNA and its protein in Swiss 3T3 fibroblasts. Consistently, C-peptide enhanced COX-2 gene promoter-activity, which was inhibited by GF109203X and Go6976, specific PKC inhibitors, and BAY11-7082, a specific nuclear factor-κB (NF-κB) inhibitor, accompanied by increased phosphorylation and degradation of IκB. These results suggest that C-peptide stimulates the transcription of inflammatory genes via activation of a PKC/IκB/NF-κB signaling pathway.

Document Type: Research article

DOI: http://dx.doi.org/10.1093/jb/mvj122

Publication date: 2006-06-01