Proinsulin C-peptide stimulates a PKC/IκB/NF-κB signaling pathway to activate COX-2 gene transcription in Swiss 3T3 fibroblasts

Masashi Kitazawa; Yasutaka Shibata; Seiichi Hashimoto; Yasushi Ohizumi; Tohru Yamakuni

doi:10.1093/jb/mvj122

Proinsulin C-peptide stimulates a PKC/IκB/NF-κB signaling pathway to activate COX-2 gene transcription in Swiss 3T3 fibroblasts

Masashi Kitazawa, Yasutaka Shibata, Seiichi Hashimoto, Yasushi Ohizumi, Tohru Yamakuni

PHA - Life and Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1083-1088
Number of pages	6
Journal	Journal of biochemistry
Volume	139
Issue number	6
DOIs	https://doi.org/10.1093/jb/mvj122
Publication status	Published - 2006 Jun

Keywords

C-peptide
Cyclooxygenase-2
Diabetes
NF-κB-dependent transcription
PKC

ASJC Scopus subject areas

Biochemistry
Molecular Biology

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title = "Proinsulin C-peptide stimulates a PKC/IκB/NF-κB signaling pathway to activate COX-2 gene transcription in Swiss 3T3 fibroblasts",

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.",

keywords = "C-peptide, Cyclooxygenase-2, Diabetes, NF-κB-dependent transcription, PKC",

author = "Masashi Kitazawa and Yasutaka Shibata and Seiichi Hashimoto and Yasushi Ohizumi and Tohru Yamakuni",

note = "Funding Information: We are grateful to Drs. N. Okino and M. Ito for the useful technical advice. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (T. Y.), the Sankyo Foundation of Life Science (T. Y.), and the Brain Science Foundation (T. Y.), and was also performed as a part of a research and development project of the Industrial Sciences and Technology Program supported by the New Energy and Industrial Technology Development Organisation (NEDO).",

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AU - Shibata, Yasutaka

AU - Hashimoto, Seiichi

AU - Ohizumi, Yasushi

AU - Yamakuni, Tohru

N1 - Funding Information: We are grateful to Drs. N. Okino and M. Ito for the useful technical advice. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (T. Y.), the Sankyo Foundation of Life Science (T. Y.), and the Brain Science Foundation (T. Y.), and was also performed as a part of a research and development project of the Industrial Sciences and Technology Program supported by the New Energy and Industrial Technology Development Organisation (NEDO).

PY - 2006/6

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N2 - 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.

AB - 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.

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Proinsulin C-peptide stimulates a PKC/IκB/NF-κB signaling pathway to activate COX-2 gene transcription in Swiss 3T3 fibroblasts

Abstract

Keywords

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