Lethal activity of FADD death domain in renal tubular epithelial cells

Fas-associated death domain (FADD) is an adaptor protein that is required for the transmission of the death signal from lethal receptors of the tumor necrosis factor superfamily. FADD contains a death domain (DD) and a death effector domain (DED). As death receptors contribute to renal tubular injur...

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Bibliographic Details
Published in:Kidney international 2006-06, Vol.69 (12), p.2205-2211
Main Authors: Justo, P., Sanz, A.B., Lorz, C., Egido, J., Ortiz, A.
Format: Article
Language:English
Subjects:
Acute Kidney Injury - genetics
Acute Kidney Injury - pathology
Acute Kidney Injury - physiopathology
Adaptor Proteins, Signal Transducing - analysis
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - physiology
Animals
apoptosis
Apoptosis - genetics
Apoptosis - physiology
Biological and medical sciences
Caspase Inhibitors
Caspases - metabolism
Cell Survival - genetics
Cell Survival - physiology
Cells, Cultured
death domain
Epithelial Cells - chemistry
Epithelial Cells - drug effects
Epithelial Cells - pathology
Epithelial Cells - physiology
FADD
Fas-Associated Death Domain Protein
Gene Expression Regulation
kidney
Kidney Tubules - chemistry
Kidney Tubules - drug effects
Kidney Tubules - pathology
Kidney Tubules - physiopathology
Medical sciences
Mice
Mice, Inbred Strains
Nephrology. Urinary tract diseases
NF-kappa B - physiology
NFκB
Protein Structure, Tertiary - genetics
Protein Structure, Tertiary - physiology
Receptors, Tumor Necrosis Factor - physiology
Serine Proteinase Inhibitors
tubular cells
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Summary:Fas-associated death domain (FADD) is an adaptor protein that is required for the transmission of the death signal from lethal receptors of the tumor necrosis factor superfamily. FADD contains a death domain (DD) and a death effector domain (DED). As death receptors contribute to renal tubular injury and tubular cell FADD increases in acute renal failure, we have studied the function of FADD in tubular epithelium. FADD expression was studied in kidney samples from mice. In order to study the contribution of FADD to renal tubular cell survival, FADD or FADD-DD were overexpressed in murine tubular epithelium. FADD is expressed in renal tubules of the healthy kidney. Both FADD and FADD-DD induce apoptosis in primary cultures of murine tubular epithelium and in the murine cortical tubular cell line. Death induced by FADD-DD has apoptotic morphology, but differs from death receptor-induced apoptosis in that it is not blocked by inhibitors of caspases. Neither an inhibitor of serine proteases nor overexpression of antiapoptotic BclxL prevented cell death. However, the combination of caspase and serine protease inhibition was protective. FADD and FADD-DD overexpression decreased nuclear factor kappa B activity. These data suggest that FADD has a death regulatory function in renal tubular cells that is independent of death receptors. FADD-DD is sufficient to induce apoptosis in these cells. This information is relevant to understanding the role of FADD in tubular injury.
ISSN:0085-2538
1523-1755
DOI:10.1038/sj.ki.5000444