Skip to main content

Advertisement

SpringerLink
Log in

Stimulation of Expression of the Intestinal Glutamine Transporter ATB0 in Tumor-Bearing Rats

  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

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 ATB0 in methyl-cholanthrene (MCA)-sarcoma bearing rats.

Methods

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 ATB0 mRNA and protein levels were measured by real-time PCR and western blot techniques, respectively.

Results

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 ATB0 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 ATB0 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).

Conclusion

Intestinal brush border membrane glutamine transport activity, transporter ATB0 mRNA and protein levels are up-regulate in tumor-bearing rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

FIG. 1.
FIG. 2.
FIG. 3.
FIG. 4.
FIG. 5.

Similar content being viewed by others

References

  1. Chance WT, Cao L, Nelson JL, Foley-Nelson T, Fischer JE. Hyperammonemia in anorectic tumor-bearing rats. Life Sci 1988; 43:67–74

    Article  PubMed  CAS  Google Scholar 

  2. Fisher JE, Chance WT. Total parenteral nutrition, glutamine and tumor growth. JPEN 1990; 14(S):86S–9S

    Google Scholar 

  3. Medina MA. Glutamine and cancer. J Nutr 2001;131(9S):2539S–42S

    PubMed  CAS  Google Scholar 

  4. Souba WW. (1991) Glutamine: Physiology, biochemistry, and nutrition in critical illness. Austin: RG Landes.

    Google Scholar 

  5. Knox WE, Horowitz ML, Friedell GH. The proportionality of glutaminase content to growth rate and morphology of rat neoplasms. Cancer Res 1969; 29:669–80

    PubMed  CAS  Google Scholar 

  6. Souba WW. Glutamine and cancer. Ann Surg 1993; 218:715–728

    Article  PubMed  CAS  Google Scholar 

  7. Medina MA, Sánchez-Jiménez F, Márquez J, Quesada AR, Núñez de Castro I. Relevance of glutamine metabolism to tumor cell growth. Mol Cell Biochem 1992; 113:1–15

    Article  PubMed  CAS  Google Scholar 

  8. Hammarqvist F, Wernerman J, Ali R, Von der Decken A, Vinnars E. Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis and improves nitrogen balance. Ann Surg 1989; 209:455–461

    Article  PubMed  CAS  Google Scholar 

  9. Chen MK, Austgen TR, Salloum RM. Skeletal muscle glutamine metabolism in the tumor bearing rat. JPEN 1991; 15(S):185

    CAS  Google Scholar 

  10. Bozzetti F, Garazzi C, Cozzaglio L, Costa A, Spinelli P, Viola G. Total parenteral nutrition and tumor growth in malnourished patients with gastric cancer. Tumori 1999; 85(3):163–6

    PubMed  CAS  Google Scholar 

  11. Cameron IL. Total parenteral nutrition in methylcholantherene-induced rat sarcoma model. Cancer Treat Rep 1981; 65(S5):137–43

    Google Scholar 

  12. Nixon DW, Moffitts S, Lawson DH, Ansley J, Lynn MJ, Kutner MH, Heymsfield SB, et al. Total parenteral nutrition as an adjunct to chemotherapy of metastatic colorectal cancer. Cancer Treat Rep 1981; 65(S5):121–8

    PubMed  Google Scholar 

  13. Austgen TR, Dudrick PS, Sitren H, Bland KI, Copeland EM, Souba WW. The effects of glutamine-enriched total parenteral nutrition on tumor growth and host tissues. Ann Surg 1992; 215:107–13

    Article  PubMed  CAS  Google Scholar 

  14. Chen MK, Austgen TR, Klimberg VS. Tumor glutamine use exceeds intestinal glutamine use in cachectic tumor bearing rats. Surg Forum 1990; 41:12–4

    Google Scholar 

  15. Souba WW, Strebel FR, Bull JM, Copeland EM, Teagtmeyer H, Cleary K. Interorgan glutamine metabolism in the tumor bearing rat. J Surg Res 1988; 44:720–6

    Article  PubMed  CAS  Google Scholar 

  16. Klimberg VS, Souba WW, Salloum RM. Glutamine enriched diets support muscle glutamine metabolism without stimulating tumor growth. J Surg Res 1990; 48:319–23

    Article  PubMed  CAS  Google Scholar 

  17. Bartlett DL, Charland S, Torosian MH. Effect of glutamine on tumor and host growth. Ann Surg Oncol 1995; 2(1):71–76

    Article  PubMed  CAS  Google Scholar 

  18. Chance WT, Cao L, Nelson JL, Fischer JE. Reduction of tumor growth following treatment with a glutamine antimetabolite. Life Sci 1988; 42:87–94

    Article  PubMed  CAS  Google Scholar 

  19. Chance WT, Cao L, Fischer JE. Insulin and acivicin improve host nutrition and prevent tumor growth during total parenteral nutrition. Ann Surg 1988; 208(4):524–31

    Article  PubMed  CAS  Google Scholar 

  20. Rouse K, Nwokedi E, Woodliff JE, Epstein J, Klimberg VS. Glutamine enhances selectivity of chemotherapy through changes in glutathione metabolism. Ann Surg 1995; 221:420–6

    Article  PubMed  CAS  Google Scholar 

  21. Burke D, Alverdy JC, Aoys E, Moss GS. Glutamine supplemented TPN improves gut immune function. Arch Surg 1989; 124:1396–9

    PubMed  CAS  Google Scholar 

  22. Souba WW, Herskowitz K, Austgen TR, Chen MK, Salloum RM. Glutamine nutrition: Theoretical considerations and therapeutic impact. JPEN 1990; 14(5):237S–43S

    CAS  Google Scholar 

  23. Fox AD, Kripke SA, DePaula J, Berman JM, Settle RG, Rombeau JL. Effect of a glutamine-supplemented enteral diet on methotrexate-induced enterocolitis. JPEN 1988; 12:325–31

    CAS  Google Scholar 

  24. Klimberg VS, Souba WW, Dolson DJ. Oral glutamine supports crypt cell turnover and accelerates intestinal healing following abdominal radiation. JPEN 1989; 13(S1):35

    Google Scholar 

  25. Stevens BR, Kaunitz J, Wright EM. Intestinal transport of amino acids and sugars: Advances using membrane vesicles. Ann Rev Physiol 1984; 417:417

    Article  Google Scholar 

  26. Salloum RM, Copeland EM, Bland KI, Souba WW. Selective stimulation of brush border glutamine transport in the tumor bearing rat. J Surg Res 1992; 50:391–7

    Article  Google Scholar 

  27. Bergmeyer HU eds. (1974) Methods of enzymatic analysis. New York: Academic.

    Google Scholar 

  28. Pan M, Meng QH, Choudry HA, Karinch AM, Lin CM, Souba WW. Stimulation of intestinal glutamine absorption in chronic metabolic acidosis. Surgery 2004; 136(2):127–34

    Article  PubMed  Google Scholar 

  29. Crabtree N, Newsholme EA. A quantitative approach to metabolic control. Curr Top Cell Regul 1985; 25:21–76

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. 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

    Haroon A. Choudry MD, Wiley W. Souba MD, ScD, ChengMao Lin PhD, QingHe Meng MD, Anne M. Karinch PhD, Jingli Huang & Ming Pan MD, PhD

Authors
  1. Haroon A. Choudry MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wiley W. Souba MD, ScD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. ChengMao Lin PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. QingHe Meng MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anne M. Karinch PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jingli Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ming Pan MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ming Pan MD, PhD.

Additional information

Presented at the 59th Society of Surgical Oncology Annual Meeting, San Diego, CA, March 23–26, 2006.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Choudry, H.A., Souba, W.W., Lin, C. et al. Stimulation of Expression of the Intestinal Glutamine Transporter ATB0 in Tumor-Bearing Rats. Ann Surg Oncol 13, 1747–1753 (2006). https://doi.org/10.1245/s10434-006-9115-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-006-9115-8

Keywords

Search

Navigation