Nuclear Translocation of a Leukocyte Elastase Inhibitor/Elastase Complex during Staurosporine-Induced Apoptosis: Role in the Generation of Nuclear L-DNase II Activity

• Published in: Experimental cell research Vol. 254; no. 1; pp. 99 - 109
• Main Authors: Belmokhtar, Chafké Ahmed, Torriglia, Alicia, Counis, Marie-France, Courtois, Yves, Jacquemin-Sablon, Alain, Ségal-Bendirdjian, Evelyne
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.01.2000
• Subjects: Ammonium Sulfate; Animals; Apoptosis; Biological Transport; Cell Nucleus - metabolism; Chemical Precipitation; cisplatin; Cytoplasm - enzymology; DNA Fragmentation; elastase; Endodeoxyribonucleases - chemistry; Endodeoxyribonucleases - isolation & purification; Endodeoxyribonucleases - metabolism; endonuclease; Enzyme Inhibitors - pharmacology; Immunoblotting; L-DNase II; L1210 leukemia cells; Leukocyte Elastase - metabolism; Mice; Nuclear Proteins - metabolism; Serpins - metabolism; staurosporine; Staurosporine - pharmacology; Time Factors; Tumor Cells, Cultured; endonuclease; elastase; staurosporine; apoptosis; L1210 leukemia cells; L-DNase II; cisplatin
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1006/excr.1999.4737

Using L1210 murine leukemia cells, we have previously shown that in response to treatment with drugs having different targets, apoptotic cell death occurs through at least two different signaling pathways. Here, we present evidence that nuclear extracts from staurosporine-treated cells elicit DNase II activity that is not detected in nuclear extracts from cisplatin-treated cells. This activity correlates with the accumulation of two nuclear proteins (70 and 30 kDa) which are detected by an anti-L-DNase II antibody. Partial purification of this DNase II activity suggests that the 30-kDa protein could be the nuclease responsible for staurosporine-induced DNA fragmentation. The 70-kDa protein is also recognized by an anti-elastase antibody, suggesting that it carries residues belonging to both L-DNase II and elastase. Since previous findings showed that L-DNase II was generated from the leukocyte inhibitor of elastase, we propose that the 70-kDa protein results from an SDS-stable association between these two proteins and is translocated from the cytoplasm to the nucleus during staurosporine-induced apoptosis.