Korean J Nephrol.  2002 Jul;21(4):569-583.

The Antiapoptotic Effect of Vascular Endothelial Growth Factor and Angiopoietin-1 on Glomerular Endothelial Cells in Adriamycin or Cisplatin-induced Apoptosis

Affiliations
  • 1Department of Internal Medicine, Chonbuk National University Medical School, Chonju, Korea. kwon@moak.chonbuk.ac.kr
  • 2Department of Research Institute of Clinical Medicine, Chonbuk National University Medical School, Chonju, Korea.
  • 3Department of Urology, Chonbuk National University Medical School, Chonju, Korea.
  • 4Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Korea.

Abstract

BACKGROUND: Because glomerular endothelium play a pivotal role in the renal diseases, damage of glomerular endothelial cells lead to progression of glomerular sclerosis and decrement of renal function. Apoptotic damage of cells is an important mechanism in renal disease. Therefore, several growth factors that have antiapoptotic effect may have a protective role in maintaining a renal function in apoptotic cell injury.
METHODS
The present study evaluated whether cisplatin or adriamycin induce apoptosis in glomerular endothelial cells. We also evaluated the antiapoptotic effect of angiopoietin-1 and VEGF in cisplatin or adriamycin- induced apoptosis.
RESULTS
Cisplatin or adriamycin induced apoptosis in glomerualr endothelial cell in dose dependent manner. Angiopoietin-1 and VEGF produced antiapoptotic effect in cisplatin or adriamycin-induced apoptosis in a dose dependent manner. The antiapoptotic effect of angiopoietin-1 was more potent than that of VEGF in glomerualr endothelial cells. Wortmannin, a phosphatidylinositol 3'-kinase inhibitor decrease the angiopoietin-1 or VEGF-induced antiapoptotic effect.
CONCLUSION
These results suggest that angiopoietin-1 and VEGF may be a strong survival factor for the glomerular endothelial cells in the cisplatin or adriamycin-induced apoptosis through phosphatidylinositol 3'-kinase/Akt. Therefore, pretreatment of angiopoietin-1 and VEGF could play a beneficial role for maintaining normal glomerular endothelial cell integrity before and during systemic cisplatin or adriamycin therapy.

Keyword

Cisplatin; Adriamycin; Antiapoptosis; Vascular endothelial growth factor; Angiopoietin-1

MeSH Terms

Angiopoietin-1*
Apoptosis*
Cisplatin
Doxorubicin*
Endothelial Cells*
Endothelium
Intercellular Signaling Peptides and Proteins
Phosphatidylinositols
Sclerosis
Vascular Endothelial Growth Factor A*
Angiopoietin-1
Cisplatin
Doxorubicin
Intercellular Signaling Peptides and Proteins
Phosphatidylinositols
Vascular Endothelial Growth Factor A
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