Metabolic acidosis stimulates intestinal glutamine absorption.
Glutamine is an essential nutrient for cell integrity during acidotic states such as shock, but the effect of extracellular pH on intestinal mucosal cell glutamine uptake is poorly understood. The purpose of this in vitro study was to investigate the intracellular signaling pathways involved in controlling intestinal glutamine transport during acidosis. Lowering the pH in the cell culture medium resulted in an increase in glutamine transport activity in a time- and pH-dependent fashion. Chronic acidosis (pH 6.6 for 48 hours) resulted in a twofold increase in glutamine transport activity (1.63+/-0.25 nmole/mg protein/minute in acidosis vs. 0.78+/-0.11 nmole/mg protein/minute in control) and a threefold increase in glutamine transport gene ATB(0) messenger RNA levels. This acidosis-induced increase in glutamine transport activity was due to a stimulation of transporter maximal transport capacity (V(max) 13.6+/-0.73 nmole/mg protein/minute in acidosis vs. 6.3+/-0.46 nmole/mg protein/minute in control) rather than a change in transporter affinity (K(m)=0.23+/-0.02 mmol/L glutamine in acidosis vs. 0.19+/-0.02 mmol/L glutamine in control). This acidosis-stimulated glutamine transport activity was blocked by actinomycin-D or cycloheximide. Cellular mitogen-activated protein kinase (MAPK) MEK1/2 and p42/44 levels were elevated in acidotic cells, and the acidosis-induced glutamine transport activity was blocked by the MAPK MEK 1 inhibitor PD 98059. Acidosis stimulates glutamine transport in Caco-2 cells via signaling pathways that lead to transcription of the glutamine transporter gene and translation of functional transporters. Mitogen-activated protein kinases are key intracellular regulators involved in this signal transduction cascade. An increased availability of glutamine to cells subjected to redox stress may help in maintaining cellular integrity.
Epler
Mark J
MJ
Department of Surgery, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Souba
Wiley W
WW
Meng
QingHe
Q
Lin
ChengMao
C
Karinch
Anne M
AM
Vary
Thomas C
TC
Pan
Ming
M
D000138:Acidosis / Q000378:metabolism*; D018938:Caco-2 Cells; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D005973:Glutamine; D020928:Mitogen-Activated Protein Kinases