Gentamicin Induced Apoptosis of Renal Tubular Epithelial (LLC-PK1) Cells.
- Author:
Kyu Hun CHOI
1
;
Tae Il KIM
;
Deug Lim CHONG
;
Ho Yung LEE
;
Dae Suk HAN
Author Information
1. Department of Internal Medicine, The Institute of Kidney Disease, Yonsei University College of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Gentamicins;
LLC-PK1 cells;
Apoptosis
- MeSH:
Animal;
Antibiotics, Aminoglycoside/toxicity*;
Antigens, CD95/analysis;
Apoptosis/drug effects*;
Cell Line;
Gentamicins/toxicity*;
Kidney Tubules, Proximal/pathology;
Kidney Tubules, Proximal/drug effects*;
Swine
- From:The Korean Journal of Internal Medicine
2000;15(3):218-223
- CountryRepublic of Korea
- Language:English
-
Abstract:
Nephrotoxicity is a major limiting factor in the use of aminoglycoside antibiotics, the mechanisms for which are still speculative. To clarify the mechanisms of renal tubular cell death induced by aminoglycosides, we examined the renal proximal tubule-like cell line, LLC-PK1, after inducing apoptosis through a chronic treatment with gentamicin (GM). Changes in the expression of the Fas were also investigated. On flow cytometric analysis, 5.7 +/- 3.3% of the control cells appeared in a region of decreased forward light scatter and increased side light scatter, where both indices represent the characteristics of apoptotic cell death. Compared to the control, treatment with 10 mM of GM for 15 days significantly increased the proportion of cells in the apoptotic region to 23.9 +/- 8.5%. This finding was supported by electrophoretic analysis of the DNA extracted from the GM-treated cells, where a series of bands corresponding to integer multiples of 180 to 200 base pairs was visualized. However, the 15-day GM treatment did not cause a significant elevation in the expression of the 45 kD Fas protein, the cell surface molecule that stimulates apoptosis, by Western blot analysis. In conclusion, long-term exposure to GM induces apoptosis of the renal tubular epithelial cells, and this process may contribute to some of the aminoglycoside nephrotoxicities. Further studies are needed on the mechanism(s) of apoptosis induced by GM.
