-Melanocyte Stimulating Hormone (MSH) decreases cyclosporine A induced apoptosis in cultured human proximal tubular cells.
10.3346/jkms.2001.16.5.603
- Author:
Sang Kyung JO
1
;
So Young LEE
;
Sang Youp HAN
;
Dae Ryong CHA
;
Won Yong CHO
;
Hyoung Kyu KIM
;
Nam Hee WON
Author Information
1. Department of Internal Medicine, Korea University College of Medicine, The Institute of Renal Disease, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
alpha-MSH;
Apoptosis;
Cyclosporine Nephrotoxicity;
Fas System
- MeSH:
Antigens, CD95/genetics;
Apoptosis/*drug effects;
Carrier Proteins/biosynthesis;
Caspases/physiology;
Cells, Cultured;
Cyclosporine/*toxicity;
Human;
Immunosuppressive Agents/*toxicity;
Kidney Tubules, Proximal/cytology/*drug effects/metabolism;
Membrane Glycoproteins/biosynthesis;
NAD+ ADP-Ribosyltransferase/metabolism;
RNA, Messenger/analysis;
alpha-MSH/*pharmacology
- From:Journal of Korean Medical Science
2001;16(5):603-609
- CountryRepublic of Korea
- Language:English
-
Abstract:
The pathogenesis of chronic cyclosporine A (CsA) nephrotoxicity has not been elucidated, but apoptosis is thought to play an important role in CsA induced tubular atrophy. Recently Fas-Fas ligand system mediated apoptosis has been frequently reported in many epithelial cells as well as in T lymphocytes. We investigated the ability of CsA to induce apoptosis in cultured human proximal tubular epithelial cells and also the effect of -MSH on them. Fas, Fas ligand, and an intracellular adaptor protein, Fas-associating protein with death domain (FADD) expression, and poly-ADP ribose polymerase (PARP) cleavage were also studied. CsA induced apoptosis in cultured tubular epithelial cells demonstrated by increased number of TUNEL positive cells and it was accompanied by a significant increase in Fas mRNA and Fas ligand protein expressions. FADD and the cleavage product of PARP also increased, indicating the activation of caspase. In -MSH co-treated cells, apoptosis markedly decreased with downregulation of Fas, Fas ligand and FADD expressions and also the cleavage product of PARP. In conclusion, these data suggest that tubular cell apoptosis mediated by Fas system may play a role in tubular atrophy in chronic CsA nephrotoxicity and pretreatment of -MSH may have a some inhibitory effect on CsA induced tubular cell apoptosis.
