Serine protease inhibitors N-α-tosyl-L-lysinyl-chloromethylketone (TLCK) and N-tosyl-L-phenylalaninyl-chloromethylketone (TPCK) do not inhibit caspase-3 and caspase-7 processing in cells exposed to pro-apoptotic inducing stimuli

✍ Scribed by Ivo Frydrych; Petr Mlejnek

• Book ID: 102304747
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 231 KB
• Volume: 105
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21971

✦ Synopsis

Abstract

We recently demonstrated that TLCK and TPCK could act as potent but nonspecific inhibitors of mature caspases [Frydrych and Mlejnek [2008] J Cell Biochem 103:1646–1656]. The question whether TLCK and TPCK inhibit simultaneously caspase activation and/or processing remained, however, open. In this article, we demonstrated that TPCK even enhanced caspase‐3 and caspase‐7 processing although it substantially inhibited caspase‐3 and caspase‐7 enzymatic (DEVDase) activity in HL‐60 cells exposed to various cell death inducing stimuli. Under the same conditions, TLCK had no effect or affected caspase‐3 and caspase‐7 processing marginally depending on cell treatment used. Importantly, TLCK substantially inhibited caspase‐3 and caspase‐7 enzymatic (DEVDase) activity irrespectively to the treatment used. Interestingly, treatment of cells with toxic concentrations of TPCK alone was accompanied by full caspase‐3 and ‐7 processing even if it induced necrosis. In contrast, treatment of cells with concentrations of TLCK that caused necrosis was accompanied by only partial caspase‐3 and caspase‐7 processing. Our results clearly indicated that TPCK and TLCK did not inhibit caspase‐3 and ‐7 enzymatic activity by prevention of their activation and/or processing. J. Cell. Biochem. 105: 1501–1506, 2008. © 2008 Wiley‐Liss, Inc.