Inhibition of mitochondrial gene transcription suppresses neurotensin secretion in the human carcinoid cell line BON

Nan Li, Qingding Wang, Jing Li, Xiaofu Wang, Mark Hellmich, Srinivasan Rajaraman, George H. Greeley, Courtney Townsend, B. Mark Evers

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Mitochondria, organelles essential for ATP production, play a central role in a number of cellular functions, including the regulation of insulin secretion. Neurotensin (NT), an important regulatory intestinal hormone, has been implicated in fatty acid translocation, gut motility and secretion, and intestinal cell growth; however, mechanisms regulating NT secretion have not been entirely defined. The purpose of this study was to determine the effect of inhibition of mitochondrial gene transcription on NT secretion. BON cells, a novel human carcinoid cell line that produces and secretes NT peptide and expresses the gene encoding NT (designated NT/N), were treated with ethidium bromide (EB; 0.05, 0.1, and 0.4 μg/ml), an inhibitor of DNA and RNA synthesis, or vehicle over a time course (1-4 days). Cells were then stimulated with either ACh (100 μM) or phorbol 12 myristate, 13-acetate (PMA, 10 nM) for 30 min. Media and cells were extracted, and NT peptide measured by RIA. Treatment with EB had no effect on BON cell viability or cell cycle distribution over the 4-day course. In contrast, EB treatment produced a dose-dependent reduction of mitochondrial gene expression; however, NT/N gene expression was not altered. Mitochondrial inhibition by EB treatment suppressed NT secretion induced by ACh and PMA, both in a dose-dependent manner. EB-mediated inhibition of NT secretion and mitochondrial gene expression was reversed with removal of EB. Our results demonstrate that inhibition of mitochondrial gene transcription suppresses both ACh- and PMA-stimulated NT release. These findings are the first to demonstrate that mitochondrial function is important for agonist-mediated NT secretion.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume288
Issue number2 51-2
DOIs
StatePublished - Feb 2005

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Neurotensin
Mitochondrial Genes
Carcinoid Tumor
Cell Line
Nucleic Acid Synthesis Inhibitors
Gene Expression
Intestinal Secretions
Gastrointestinal Hormones
Peptides
Gastrointestinal Motility
Ethidium
Organelles
Cell Survival
Cell Cycle
Mitochondria
Acetates
Fatty Acids
Adenosine Triphosphate

Keywords

  • Gut endocrine cells
  • Peptide secretion

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Inhibition of mitochondrial gene transcription suppresses neurotensin secretion in the human carcinoid cell line BON. / Li, Nan; Wang, Qingding; Li, Jing; Wang, Xiaofu; Hellmich, Mark; Rajaraman, Srinivasan; Greeley, George H.; Townsend, Courtney; Evers, B. Mark.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 288, No. 2 51-2, 02.2005.

Research output: Contribution to journalArticle

Li, Nan ; Wang, Qingding ; Li, Jing ; Wang, Xiaofu ; Hellmich, Mark ; Rajaraman, Srinivasan ; Greeley, George H. ; Townsend, Courtney ; Evers, B. Mark. / Inhibition of mitochondrial gene transcription suppresses neurotensin secretion in the human carcinoid cell line BON. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2005 ; Vol. 288, No. 2 51-2.
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