Changes of Serum Inflammatory Markers after Gamma-Secretase Inhibitor Administration Mice

Document Type : Original Article (s)

Authors

1 Associate professor, Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2 Students Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

3 PhD Student, Department of Physiology, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Notch signaling is involved in physiological and pathological processes and gamma-secretase inhibitors can suppress it. The aim of this study was to evaluate the effect of DAPT, a gamma secretase inhibitor, on serum inflammatory markers in mice.Methods: 24 C57BL6 mice (age: 5 weeks old) were randomly divided into control and obese groups. Obese group received high-fat diet (60% fat, 20% protein, and 20% carbohydrate) for 20 weeks. Control group received standard diet during this time. Then, each group was divided into receiving and non-receiving DAPT (50mg/kg; Subcutaneous). After 14 days, blood samples were taken for measurements of serum high-sensitive C-reactive protein (hs-CRP) and interlukin-6 (IL-6).Findings: There was no significant difference in serum hs-CRP concentration between control and obese groups (P > 0.05). Administration of DAPT did not alter serum hs-CRP level in both groups (P > 0.05). Serum Il-6 was significantly higher in obese animals compare to controls (P < 0.05) and administration of DAPT reduced serum IL-6 in control and obese animals (P < 0.05).Conclusion: DAPT, as a gamma secretase inhibitor, could affect several physiological and pathological vascular changes by alteration of serum inflammatory markers.

Keywords

References

  1. Rehman AO, Wang CY. Notch signaling in the regulation of tumor angiogenesis. Trends Cell Biol 2006; 16(6): 293-300.
  2. Leong KG, Karsan A. Recent insights into the role of Notch signaling in tumorigenesis. Blood 2006; 107(6): 2223-33.
  3. Cao L, Arany PR, Wang YS, Mooney DJ. Promoting angiogenesis via manipulation of VEGF responsiveness with notch signaling. Biomaterials 2009; 30(25): 4085-93.
  4. Wang M, Wu L, Wang L, Xin X. Down-regulation of Notch1 by gamma-secretase inhibition contributes to cell growth inhibition and apoptosis in ovarian cancer cells A2780. Biochem Biophys Res Commun 2010; 393(1): 144-9.
  5. Nakajima M, Yuasa S, Ueno M, Takakura N, Koseki H, Shirasawa T. Abnormal blood vessel development in mice lacking presenilin-1. Mech Dev 2003; 120(6): 657-67.
  6. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004; 4(8): 579-91.
  7. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000; 407(6801): 249-57.
  8. Saeidi H, Shabani Kia N, Kalantari E, Tahergorabi Z, Khazaei M. Effects of DAPT on serum vascular endothelial growth factor and its soluble receptor in obese BALB/C mice. J Isfahan Med Sch 2013; 30(214): 1942-8. [In Persian].
  9. Paris D, Quadros A, Patel N, DelleDonne A, Humphrey J, Mullan M. Inhibition of angiogenesis and tumor growth by beta and gamma-secretase inhibitors. Eur J Pharmacol 2005; 514(1): 1-15.
  10. Portelius E, Zhang B, Gustavsson MK, Brinkmalm G, Westman-Brinkmalm A, Zetterberg H, et al. Effects of gamma-secretase inhibition on the amyloid beta isoform pattern in a mouse model of Alzheimer's disease. Neurodegener Dis 2009; 6(5-6): 258-62.
  11. Rodriguez-Hernandez H, Simental-Mendia LE, Rodriguez-Ramirez G, Reyes-Romero MA. Obesity and inflammation: epidemiology, risk factors, and markers of inflammation. Int J Endocrinol 2013; 2013: 678159.
  12. Bisoendial RJ, Boekholdt SM, Vergeer M, Stroes ES, Kastelein JJ. C-reactive protein is a mediator of cardiovascular disease. Eur Heart J 2010; 31(17): 2087-91.
  13. Slevin M, Krupinski J. A role for monomeric C-reactive protein in regulation of angiogenesis, endothelial cell inflammation and thrombus formation in cardiovascular/cerebrovascular disease? Histol Histopathol 2009; 24(11): 1473-8.
  14. Wei Z, Chigurupati S, Arumugam TV, Jo DG, Li H, Chan SL. Notch activation enhances the microglia-mediated inflammatory response associated with focal cerebral ischemia. Stroke 2011; 42(9): 2589-94.
Journal of Isfahan Medical School
Volume 31, Issue 233 - Serial Number 233
March and April 2013
Pages 486-492

Files

History

  • Receive Date: 28 May 2013
  • Revise Date: 28 April 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics