RRC ID 18727
著者 Nose S, Wasa M, Tazuke Y, Owari M, Fukuzawa M.
タイトル Cisplatin upregulates glutamine transport in human intestinal epithelial cells: the protective mechanism of glutamine on intestinal mucosa after chemotherapy.
ジャーナル JPEN J Parenter Enteral Nutr
Abstract BACKGROUND:Glutamine (GLN) prevents the intestinal mucosal injury induced by chemotherapy, although the mechanism of this protective action has not yet been elucidated. Amino acid transport across the plasma membrane is essential for supplying enterocytes with amino acids for cellular metabolism. It was hypothesized that chemotherapy stimulates GLN transport, which enables GLN to be used more efficiently as a metabolic fuel.
METHODS:A rat model was used to examine the effect of enteral GLN on intestinal mucosal injury induced by intraperitoneal injection of cisplatin (7.0 mg/kg of body weight). The effects of cisplatin on amino acid transport and the expression of messenger RNA and protein were evaluated by real-time polymerase chain reaction and Western blot analysis, respectively, in the human intestinal epithelial cell line Caco-2. The effects of cisplatin on glutaminase activity and intracellular glutathione were also studied.
RESULTS:GLN prevented mucosal atrophy induced by cisplatin in rats. In Caco-2 cells, cisplatin significantly increased GLN transport and the expression of GLN transporter ASCT2 messenger RNA and protein. Leucine, but not glutamate, transport significantly increased in the cisplatin-treated group due to the increase in LAT1 (leucine transporter) protein expression. Glutaminase activity and intracellular glutathione increased significantly in the cisplatin-treated group.
CONCLUSIONS:Bolus enteral GLN prevents intestinal mucosal injury induced by cisplatin in rats, as demonstrated by increased GLN transport and increased GLN transporter expression after cisplatin administration.
巻・号 34(5)
ページ 530-7
公開日 2010-1-1
DOI 10.1177/0148607110362694
PII 34/5/530
PMID 20852181
MeSH Amino Acid Transport System ASC / genetics Amino Acid Transport System ASC / metabolism Animals Antineoplastic Agents / adverse effects Antineoplastic Agents / pharmacology* Biological Transport / drug effects Blotting, Western Caco-2 Cells Carrier Proteins / metabolism Cisplatin / adverse effects Cisplatin / pharmacology* Enteral Nutrition Epithelial Cells / drug effects* Epithelial Cells / metabolism Epithelial Cells / pathology Gastrointestinal Agents / pharmacology Gastrointestinal Agents / therapeutic use* Glutaminase / metabolism Glutamine / metabolism Glutamine / pharmacology Glutamine / therapeutic use* Glutathione / metabolism Humans Intestinal Mucosa / drug effects* Intestinal Mucosa / metabolism Intestinal Mucosa / pathology Leucine / metabolism Male Minor Histocompatibility Antigens Models, Animal Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction Up-Regulation
IF 2.853
引用数 11
WOS 分野 NUTRITION & DIETETICS
リソース情報
ヒト・動物細胞 CACO-2(RCB0988)