Skip to main content

Advertisement

Log in

High Glucose Levels Down-Regulate Glucose Transporter Expression That Correlates With Increased Oxidative Stress in Placental Trophoblast Cells In Vitro

  • Original Articles
  • Published:
The Journal of the Society for Gynecologic Investigation: JSGI Aims and scope Submit manuscript

Abstract

Objective

To study glucose transporter expression and oxidative stress in placental trophoblasts under hyperglycemic conditions in vitro.

Methods

Trophoblasts were isolated from term normal human placentas and incubated with Dulbecco’s modified eagle medium containing 1000, 2500, and 4500 mg/L glucose for 3 days. At the end of incubation, culture medium was collected. Trophoblast RNA was extracted and mRNA expression of glucose transporters was determined by RNase protection assay. Messenger RNA expression for copper-zinc-superoxide dismutase (CuZn-SOD) was determined by real-time polymerase chain reaction. Lipid peroxide production was determined by measuring malondialdehyde concentration in the culture supernatant. Protein expression of sodium-glucose transporter 2 (SGLT-2) was determined by Western blot analysis.

Results

Messenger RNA expression for glucose transporter 1 (GLUTI) and SGLT-2 were reduced in trophoblast cells incubated with 4500 mg/L glucose compared with those incubated with 1000 and 2000 mg/L glucose. mRNA expression of CuZn-SOD was also decreased in trophoblasts incubated with 4500 mg/L glucose. Malondialdehyde production was significantly increased by trophoblasts incubated with 4500 mg/L glucose compared with those by trophoblasts incubated with WOO and 2000 mg/L glucose (4.69 ± 0.60 versus 2.W ± 0.29 and 2.89 ± 0.47 nmol/mg protein; P <.01, respectively).

Conclusions

Down-regulation of gene expression of glucose transporters correlates with increased lipid peroxide production and decreased superoxide dismutase expression in placental trophoblasts cultured under hyperglycemic conditions.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Sibley CP, Boyd RDH. Mechanisms of transfer across the human placenta. In: Polin RA, Fox WW, eds. Fetal and neonatal physiology. Vol 1. Philadelphia: Saunders, 1992:62–74.

    Google Scholar 

  2. Hahn T, Barth S, Graf R, et al. Placental glucose transporter expression is regulated by glucocorticoids. J Clin Endocrinol Metab 1999;84:1445–52.

    CAS  PubMed  Google Scholar 

  3. Illsley NP. Glucose transporters in the human placenta. Placenta 2000;21:14–22.

    Article  CAS  PubMed  Google Scholar 

  4. Ceriello A. Oxidative stress and glycemic regulation. Metabolism 2000;49(Suppl 1):27–9.

    Article  CAS  PubMed  Google Scholar 

  5. Walsh SW, Wang Y. Trophoblast and placental villous core production of lipid peroxides, thromboxane, and prostacyclin in preeclampsia. J Clin Endocrinol Metab 1995;80:1888–93.

    CAS  PubMed  Google Scholar 

  6. Wang Y, Walsh SW. Increased superoxide generation is associated with decreased superoxide dismutase activity and mRNA expression in placental trophoblast cells in preeclampsia. Placenta 2001;22:206–12.

    Article  CAS  PubMed  Google Scholar 

  7. Jentzsch AM, Bachmann H, Furst P, et al. Improved analysis of malondialdehyde in human body fluids. Free Radical Biol Med 1996;20:251–6.

    Article  CAS  Google Scholar 

  8. Livak KJ. ABI Prism 7700 sequence detection system: User bulletin 2. Foster City, CA: PE Applied Biosystems, 1997.

    Google Scholar 

  9. Johnson MR, Wang K, Smith JB, et al. Quantitation of dihydropyrimidine dehydrogenase expression by real-time reverse transcription polymerase chain reaction. Anal Biochem 2000;278:175–84.

    Article  CAS  PubMed  Google Scholar 

  10. Hahn T, Hahn D, Blaschitz A, et al. Hyperglycaemia-induced subcellular redistribution of GLUTI glucose transporters in cultured human term placental trophoblast cells. Diabetologia 2000;43:173–80.

    Article  CAS  PubMed  Google Scholar 

  11. Catherwood MA, Powell LA, Anderson P, et al. Glucose-induced oxidative stress in mesangial cells. Kidney Int 2002;61:599–608.

    Article  CAS  PubMed  Google Scholar 

  12. Hauguel-de Mouzon S, Leturque A, Alsat E, et al. Developmental expression of Gluti glucose transporter and c-fos genes in human placental cells. Placenta 1994;15:35–46.

    Article  Google Scholar 

  13. Barth S, Hahn T, Zechner R, et al. Prolonged hyperglycemia in vitro affects glucose transporter protein GLUTI and glucose uptake in cultured term trophoblast cells. Placenta 1994;15:A4.

    Article  Google Scholar 

  14. Hahn T, Barth S, Weiss U, et al. Sustained hyperglycemia in vitro down-regulates the GLUTI glucose transport system of cultured human term placental trophoblast: A mechanism to protect fetal development? FASEB J 1998;12:1221–31.

    Article  CAS  PubMed  Google Scholar 

  15. Illsley NP, Sellers MC, Wright PX. Glycaemic regulation of glucose transporter expression and activity in the human placenta. Placenta 1998;19:517–24.

    Article  CAS  PubMed  Google Scholar 

  16. Jansson T, Wennergren M, Illsley NP. Glucose transporter protein expression in human placenta throughout gestation and in intrauterine growth retardation. J Clin Endocrinol Metab 1993;77:1554–62.

    CAS  PubMed  Google Scholar 

  17. Jansson T, Wennergren M, Powell TL. Placental glucose transport and GLUT 1 expression in insulin-dependent diabetes. Am J Obstet Gynecol 1999;180:163–8.

    Article  CAS  PubMed  Google Scholar 

  18. Illsley NP. Placental glucose transport in diabetic pregnancy. Clin Obstet Gynecol 2000;43:116–26.

    Article  CAS  PubMed  Google Scholar 

  19. Gaither K, Quraishi AN, Illsley NP. Diabetes alters the expression and activity of the human placental GLUTI glucose transporter. J Clin Endocrinol Metab 1999;84:695–701.

    CAS  PubMed  Google Scholar 

  20. Ceriello A, Quagliaro L, Catone B, et al. Role of hyperglycemia in nitrotyrosine postprandial generation. Diabetes Care 2002;25:1439–43.

    Article  CAS  PubMed  Google Scholar 

  21. Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care 1996;19:257–67.

    Article  CAS  PubMed  Google Scholar 

  22. Mercuri F, Quagliaro L, Ceriello A. Oxidative stress evaluation in diabetes. Diabetes Technol Ther 2000;2:589–600.

    Article  CAS  PubMed  Google Scholar 

  23. Lipinski B. Pathophysiology of oxidative stress in diabetes mellitus. J Diabetes Complications 2001;15:203–10.

    Article  CAS  PubMed  Google Scholar 

  24. Jansson T, Ekstrand Y, Wennergren M, et al. Placental glucose transport in gestational diabetes mellitus. Am J Obstet Gynecol 2001;184:111–6.

    Article  CAS  PubMed  Google Scholar 

  25. Wright EM. Renal Na+-glucose cotransporters. Am J Physiol Renal Physiol 2001;280(1):F10–8.

    Article  CAS  PubMed  Google Scholar 

  26. Wallner EI, Wada J, Tramonti G, et al. Status of glucose transporters in the mammalian kidney and renal development. Renal Failure 2001;23:301–10.

    Article  CAS  PubMed  Google Scholar 

  27. Prasad PD, Huang W, Wang H, et al. Transport mechanisms for vitamin C in the JAR human placental choriocarcinoma cell line. Biochim Biophys Acta 1998;1369:141–51.

    Article  CAS  PubMed  Google Scholar 

  28. Ingermann RL, Stankova L, Bigley RH. Role of monosaccharide transporter in vitamin C uptake by placental membrane vesicles. Am J Physiol 1986;250:C637–41.

    Article  CAS  PubMed  Google Scholar 

  29. Rybakowski C, Mohar B, Wohlers S, et al. The transport of vitamin C in the isolated human near-term placenta. Eur J Obstet Gynecol Reprod Biol 1995;62:107–14.

    Article  CAS  PubMed  Google Scholar 

  30. Nishizaki T, Toshiyuki M. Low glucose enhances Na+/glucose transport in bovine brain artery endothelial cells. Stroke 1998;29:844–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yuping Wang MD, PhD.

Additional information

This work was supported in part by grant HD36822 from the National Institute Child Health Development and by grant HL 65997 from the National Heart, Blood and Lung Institute.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, H., Gu, Y., Zhang, Y. et al. High Glucose Levels Down-Regulate Glucose Transporter Expression That Correlates With Increased Oxidative Stress in Placental Trophoblast Cells In Vitro. Reprod. Sci. 11, 75–81 (2004). https://doi.org/10.1016/j.jsgi.2003.08.002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1016/j.jsgi.2003.08.002

Key words

Navigation