Multiple proteases are involved in thymocyte apoptosis.

Abstract:

:To investigate the involvement of proteases in apoptosis, rat thymocytes were treated with the glucocorticoid hormone methylprednisolone or the topoisomerase II inhibitor etoposide in the presence of selective substrate inhibitors of either interleukin-1 beta-converting enzyme (ICE), (Z-Val-Ala-Asp-chloromethylketone, VADcmk) or Ca(2+)-regulated serine protease (Suc-Ala-Ala-Pro-Phe-chloromethylketone, AAPFcmk). VADcmk protected from lamin proteolysis, chromatin fragmentation, cell shrinkage, and formation of apoptotic nuclei in both methylprednisolone- and etoposide-treated thymocytes when present during the initiation of the apoptotic process. AAPFcmk prevented lamin breakdown, chromatin fragmentation, and apoptotic morphological changes in thymocytes treated with methylprednisolone, but not with etoposide. Both MPS- and etoposide-treated thymocytes exhibited enhanced ICE-like protease activity which was maximal 1 h after treatment. This increase in proteolytic activity was blocked by VADcmk, but not AAPFcmk. Our findings suggest that ICE-like protease activity is critically involved in the early phase of both methylprednisolone- and etoposide-induced apoptosis in thymocytes, whereas the Ca(2+)-regulated serine protease is an obligatory component of the proteolytic cascade in methylprednisolone-induced apoptosis.

journal_name

Exp Cell Res

authors

Zhivotovsky B,Gahm A,Ankarcrona M,Nicotera P,Orrenius S

doi

10.1006/excr.1995.1391

subject

Has Abstract

pub_date

1995-12-01 00:00:00

pages

404-12

issue

2

eissn

0014-4827

issn

1090-2422

pii

S0014-4827(85)71391-2

journal_volume

221

pub_type

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