Protein kinase C activation of intestinal glutamine transport is mediated by mitogen-activated protein kinases

Ming Pan, Christopher A. Wolfgang, Anne M. Karinch, Cheng Mao Lin, Qing He Meng, Thomas C. Vary, Wiley W. Souba

Research output: Contribution to journalArticle

Abstract

Background. Glutamine is essential for the preservation of intestinal structure and function and its uptake by the bowel is augmented during catabolic states. However, the signal transduction pathways implicated in brush border glutamine transport have not been examined. The aim of this study was to investigate the intracellular signaling pathways involved in the regulation of accelerated intestinal glutamine transport. Our hypothesis was that the activation of intestinal glutamine transport involves protein kinase C (PKC) and is mediated by mitogen-activated protein kinases (MAPKs). Methods. [3H]L-Glutamine (50 μM) transport activity and mRNA levels for the intestinal glutamine transporter ATB0 were measured in intestinal epithelial Caco-2 cells. Confluent cells were treated with phorbol ester (PMA, 0-10 μM), the MAPK MEK inhibitor PD 98059 (0-100 μM), actinomycin (0-0.1 μM), MAPK p38 inhibitor SB 203580 (0-10 μM), protein kinase C inhibitor chelerythrine chloride (0-6.6 μM), or cycloheximide (0-10 μM) for 24 h. Data were analyzed by ANOVA with significance set at P < 0.05. Results. Phorbol ester treatment increased intestinal System B glutamine transport activity by 75%, an increase that was blocked individually by PD 98059, chelerythrine chloride, actinomycin, and cycloheximide, but not SB 203580, an effect first noted at 6 h. The resulting activity increase was consistent with de novo synthesis of transporter units and enhanced expression of transporter gene ATB0 as indicated by a threefold increase of ATB0 mRNA levels in PMA-treated cells. Conclusions. Activation of glutamine transport in Caco-2 cells by phorbol ester occurs via signaling pathways that lead to transcription of the glutamine transporter gene. PKC and mitogen-activate protein kinase MEK are key intracellular mediators involved in this signal transduction cascade.

Original languageEnglish (US)
Pages (from-to)137-144
Number of pages8
JournalJournal of Surgical Research
Volume106
Issue number1
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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