Tumor necrosis factor α inhibits transcriptional activity of the porcine P-45011A insulin-like growth factor response element

Randall Urban, Manubai Nagamani, Yvonne Bodenburg

Research output: Contribution to journalArticle

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Abstract

We investigated the effects of tumor necrosis factor α (TNFα) on the transcriptional activity of the porcine P-45011A (P450scc) insulin-like growth factor response element (IGFRE). TNFα inhibited insulin-like growth factor-I (IGF-I)-stimulated P450scc mRNA concentrations in cultures of porcine granulosa cells. Transient transfection experiments in granulosa cells with deletion P450scc/luciferase constructs showed that TNFα inhibited the transcriptional activity of the IGFRE. IGF-I binding and IGF-I receptor mRNA concentrations in porcine granulosa cells were not inhibited by TNFα. Electrophoretic mobility shift assay with nuclear extract protein from porcine granulosa cells treated with IGF-I and TNFα showed that Sp1 and a second transcription factor, P2, bound to the IGFRE. While IGF-I treatment increased the binding activity of both factors, TNFα specifically inhibited the IGF-I-stimulated binding activity of P2. Transient transfection studies done in mouse fibroblasts overexpressing the IGF-I receptor (NWTb3) with the porcine IGFRE (three repeats) in an SV40/luciferase construct also showed TNFα inhibited IGF-I-stimulated reporter gene expression. We conclude that TNFα inhibits the transcriptional activity of the porcine P450scc IGFRE by preventing IGF-I-stimulated binding of P2.

Original languageEnglish (US)
Pages (from-to)31699-31703
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number49
DOIs
StatePublished - 1996

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Response Elements
Somatomedins
Insulin-Like Growth Factor I
Swine
Tumor Necrosis Factor-alpha
Granulosa Cells
Insulin, Regular, Pork
IGF Type 1 Receptor
Luciferases
Transfection
Electrophoretic mobility
Messenger RNA
Electrophoretic Mobility Shift Assay
Fibroblasts
Nuclear Proteins
Reporter Genes
Gene expression
Assays
Transcription Factors
Gene Expression

ASJC Scopus subject areas

  • Biochemistry

Cite this

Tumor necrosis factor α inhibits transcriptional activity of the porcine P-45011A insulin-like growth factor response element. / Urban, Randall; Nagamani, Manubai; Bodenburg, Yvonne.

In: Journal of Biological Chemistry, Vol. 271, No. 49, 1996, p. 31699-31703.

Research output: Contribution to journalArticle

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