Cathepsin L is involved in cathepsin D processing and regulation of apoptosis in A549 human lung epithelial cells.
Cathepsins are implicated in a multitude of physiological and pathophysiological processes. The aim of the present study was to investigate the function of cathepsin L (catL) in the proteolytic network of human lung epithelial cells and its role in the regulation of apoptosis. We found that catL-deficient A549 cells as well as lung tissue extracts of catL(-/-) mice express increased amounts of single-chain cathepsin D (catD). Degradation experiments indicate that catL specifically degrades the single-chain isoform of catD. Furthermore, we found that catL-deficient cells showed increased sensitivity to apoptosis. Finally, we demonstrate that the inhibition of catD activity by pepstatin A decreased the number of apoptotic cells in catL-deficient A549 cells after anti-Fas treatment. In conclusion, catL is involved in catD processing and the accumulation of catD isoforms in catL-deficient cells is associated with increased rates of spontaneous and anti-Fas-induced apoptosis.
Institute of Immunology, Otto-von-Guericke-University Magdeburg, Leipziger-Str. 44, D-39120 Magdeburg Germany.
Aline
A
Wille
Annegret
A
Gerber
Anke
A
Heimburg
Anita
A
Reisenauer
Christoph
C
Peters
Paul
P
Saftig
Thomas
T
Reinheckel
Tobias
T
Welte
Frank
F
Bühling
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002402:Cathepsin D / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D056668:Cathepsin L; D002403:Cathepsins / Q000187:drug effects / Q000502:physiology*; D003546:Cysteine Endopeptidases; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000502:physiology; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010436:Pepstatins / Q000494:pharmacology
D016376:Oligonucleotides, Antisense; D010436:Pepstatins; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C534278:Ctsl protein, mouse; D002402:Cathepsin D; C031375:pepstatin