Choudry Haroon A, Souba Wiley W, Lin Chengmao, Meng Qinghe, Karinch Anne M, Huang Jingli, Pan Ming
Department of Surgery, The Milton S. Hershey Medical Center, The Pennsylvania State University, College of Medicine, 500 University Drive, P.O. Box MC 850, Hershey, PA 17033, USA.
Ann Surg Oncol. 2006 Dec;13(12):1747-53. doi: 10.1245/s10434-006-9115-8. Epub 2006 Sep 28.
Glutamine supplementation ameliorates host catabolic response in tumor bearing states. The purpose of this in vivo study was to investigate intestinal glutamine transport and expression of glutamine transporter ATB(0) in methyl-cholanthrene (MCA)-sarcoma bearing rats.
Fisher-344 rats underwent subcutaneous flank implantation of MCA-sarcoma cells (saline as control) and were pair-fed an equal quantity of chow as controls, to account for tumor-induced anorexia, until tumors reached 10 or 20% body weight. Intestinal mucosal brush border membrane [3H]-Glutamine transport was measured. Glutamine transporter ATB(0) mRNA and protein levels were measured by real-time PCR and western blot techniques, respectively.
Glutamine transport activity across the intestinal brush border membrane (BBM) was 3.7-fold higher in tumor-bearing rats (TBR) than in controls (TBR 153 +/- 22.6 vs. Control 41.9 +/- 9.7 pmol/mg protein/10s, P < .01). Transporter ATB(0) mRNA levels were 1.4-fold higher in tumor-bearing rats (Relative value TBR .61 +/- .12 vs. Control .43 +/- .1, P < .05). A 1.4-fold increase in transporter ATB(0) protein levels was observed in the tumor-bearing rats (Relative value TBR .52 +/- .07 vs. Control .37 +/- .04, P < .05). Circulating aortic plasma glutamine levels were 1.3-fold higher in tumor bearing rats ([Glutamine] = .63 +/- .02 Control vs. [Glutamine] = .74 +/- .01 mmol/l TBR, P < .0001). Portal venous plasma glutamine levels were also higher in tumor bearing rats ([Glutamine] = .47 +/- .01 Control vs. [Glutamine] = .60 +/- .02 mmol/l TBR, P < .0001).
Intestinal brush border membrane glutamine transport activity, transporter ATB(0) mRNA and protein levels are up-regulate in tumor-bearing rats.
补充谷氨酰胺可改善荷瘤状态下宿主的分解代谢反应。本体内研究的目的是调查甲基胆蒽(MCA)肉瘤荷瘤大鼠肠道谷氨酰胺转运及谷氨酰胺转运体ATB(0)的表达情况。
将MCA肉瘤细胞皮下植入Fisher-344大鼠的侧腹(以生理盐水作为对照),并与对照组大鼠配对喂养等量食物,以考虑肿瘤引起的厌食情况,直至肿瘤重量达到体重的10%或20%。测量肠黏膜刷状缘膜[3H] - 谷氨酰胺转运情况。分别通过实时PCR和蛋白质印迹技术测量谷氨酰胺转运体ATB(0)的mRNA和蛋白质水平。
荷瘤大鼠(TBR)肠道刷状缘膜(BBM)的谷氨酰胺转运活性比对照组高3.7倍(TBR为153±22.6,对照组为41.9±9.7 pmol/mg蛋白质/10秒,P <.01)。荷瘤大鼠转运体ATB(0)的mRNA水平比对照组高1.4倍(TBR相对值为0.61±0.12,对照组为0.43±0.1,P <.05)。在荷瘤大鼠中观察到转运体ATB(0)的蛋白质水平增加了1.4倍(TBR相对值为0.52±0.07,对照组为0.37±0.04,P <.05)。荷瘤大鼠主动脉循环血浆谷氨酰胺水平比对照组高1.3倍(对照组谷氨酰胺浓度为0.63±0.02,荷瘤大鼠为0.74±0.01 mmol/l,P <.0001)。荷瘤大鼠门静脉血浆谷氨酰胺水平也更高(对照组谷氨酰胺浓度为0.47±0.01,荷瘤大鼠为0.60±0.02 mmol/l,P <.0001)。
荷瘤大鼠肠道刷状缘膜谷氨酰胺转运活性、转运体ATB(0)的mRNA和蛋白质水平上调。