Effect of protease inhibitors on early events of apoptosis

Experimental Cell Research
S HaraZ Darzynkiewicz

Abstract

Proteolysis is an early event of apoptosis which appears to be associated with activation of the endonuclease which is responsible for internucleosomal DNA cleavage. The present study was designed to reveal the possible role of proteolysis in other early events, such as chromatin condensation, nuclear breakdown, and destabilization of in situ DNA double-stranded structure. Apoptosis of human leukemic HL-60 cells and rat thymocytes was induced by different agents, including DNA topoisomerase inhibitors, an RNA antimetabolite, and the glucocorticosteroid, prednisolone. DNA degradation was evaluated by pulsed field and conventional gel electrophoresis and by the presence of in situ DNA strand breaks. DNA stability was estimated by the measure of its sensitivity in situ to denaturation. Chromatin condensation, nuclear breakdown, and other morphological changes were monitored by interference contrast and UV microscopy following cell staining with the DNA-specific fluorochrome 4',6-diamidino-2- phenylindole. Several irreversible or reversible serine protease inhibitors prevented internucleosomal DNA degradation, nuclear breakdown, and destabilization of DNA double-stranded structure. The effective inhibitors, however, did not prevent...Continue Reading

Citations

Aug 5, 2011·American Journal of Physiology. Cell Physiology·Julia L CookRichard N Re
Dec 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·E AhlbomS Ceccatelli
Apr 13, 2010·Biochemical and Biophysical Research Communications·Z Fabian, H O Fearnhead
Nov 27, 2008·European Journal of Pharmacology·Teja CelharIrena Mlinaric-Rascan
Aug 5, 2009·Apoptosis : an International Journal on Programmed Cell Death·Z FabianH O Fearnhead
Mar 19, 1999·Cytometry·E BednerZ Darzynkiewicz
Jan 30, 2004·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Deding TaoJianping Gong
Mar 10, 1998·Journal of Cellular Physiology·J M CoboH A Crissman
Jan 1, 1997·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·P R Walker, M Sikorska
Jan 19, 2005·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Malcolm Anthony King
Oct 5, 2001·Free Radical Biology & Medicine·O Ullrich, T Grune
Jul 20, 2002·Experimental Cell Research·Jerzy GrabarekZbigniew Darzynkiewicz

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis