J Korean Med Sci.  2001 Oct;16(5):603-609. 10.3346/jkms.2001.16.5.603.

-Melanocyte Stimulating Hormone (MSH) decreases cyclosporine A induced apoptosis in cultured human proximal tubular cells

• Jo SK
• Lee SY
• Han SY
• Cha DR
• Cho WY
• Kim HK
• Won NH

• KMID: 2157569
• DOI: http://doi.org/10.3346/jkms.2001.16.5.603

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.

Keyword

alpha-MSH; Apoptosis; Cyclosporine Nephrotoxicity; Fas System

MeSH Terms

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