Na+-dependent Neutral Amino Acid Transporter ASCT2 Is Downregulated in Seriously Traumatized Human Intestinal Epithelial Cells
Serious trauma to the body often is associated with changes in protein metabolism in multiple organs and tissues. Clinically, the catabolic response results in a generalized negative nitrogen balance. Nutrition support has been an important component of the care of seriously traumatized patients. However, during states of severe trauma, enterocyte transport function remains unclear. This study aims to quantitate the Na+-dependent neutral amino acid transport and expression of its transporter in traumatically injured Caco-2 cell lines.
Transport and transporter of Na+-dependent neutral amino acid in Caco-2 cell lines were characterized. Then the cell lines were cultured under hypoxic, nutrient-deprived, and ischemic conditions for 1, 2, 4, and 6 hours. After severe trauma was performed, we investigated the transport of Na+-dependent neutral amino acids and the expression of transporter protein and mRNA in apical membrane vesicles.
Among the neutral amino acid transporters, only ASCT2 mRNA was amplified successfully. Under nutrient-deprived and ischemic conditions, transport of L-alanine and L-glutamine decreased significantly compared with control (P < 0.01), whereas hypoxia had no significant effect. The changes were associated with a decrease in maximum transport velocity without an influence on transport affinity. Expression of relative transporter proteins and mRNA decreased significantly compared with control (P < 0.01).
Na+-dependent neutral amino acid transport and its key transporter are differently regulated during state of traumatic injury. It may be of use to provide some strategies targeting the special nutrient requirements and transport capabilities of seriously traumatized patients.
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ABSTRACT: The transport of fluid, nutrients and electrolytes to and from the intestinal lumen is a primary function of epithelial cells. Normally, the intestine absorbs approximately 9L of fluid and 1 kg of nutrients daily, driven by epithelial transport processes that consume large amounts of cellular energy and O2. The epithelium exists at the interface of the richly vascularised mucosa and the anoxic luminal environment and this steep O2 gradient plays a key role in determining the expression pattern of proteins involved in fluid, nutrient and electrolyte transport. However, the dynamic nature of the splanchnic circulation necessitates that the epithelium can evoke co-ordinated responses to fluctuations in O2 availability, which occur either as a part of the normal digestive process or as a consequence of several pathophysiological conditions. While it is known that hypoxia responsive signals, such as reactive oxygen species, AMP-activated kinase, hypoxia-inducible factors, and prolyl hydroxylases are all important in regulating epithelial responses to altered O2 supply, our understanding of the molecular mechanisms involved is still limited. Here, we aim to review the current literature regarding the role that O2 plays in regulating intestinal transport processes and to highlight areas of research that still need to be addressed.This article is protected by copyright. All rights reserved
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