Activation of poly(ADP-ribose)polymerase in apoptotic human cells

作者: R Bernardi , C Negri , M Donzelli , F Guano , Mauro Torti

DOI: 10.1016/0300-9084(96)88150-8

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摘要: Abstract We have studied the effect of chemotherapeutic drug VP-16 (etoposide) on metabolism HeLa cells by analysing different cellular parameters considered as markers apoptosis. Typical features such chromatin condensation and internucleosomal DNA cleavage are visible in exposed to VP-16. investigated whether appearance small-sized fragments could regulate ADP-ribosylation process. To this purpose, we analysed, means activity gel technique, structural catalytical properties poly(ADP-ribose)polymerase. In extracts from where etoposide-induced fragmentation occurred, shown that label autoribosylated form enzyme is greatly increased even if amount protein remains constant. This phenomenon completely abolished preincubated with poly(ADP-ribose)polymerase inhibitor, 3-aminobenzamide. After administration, observed level NAD not heavily decreased. It widely agreed zinc exerts an inhibitory endonuclease(s) responsible for during incubation zinc/VP-16 found occurrence apoptotic absence cleavage. The inhibition prevents activation activity. These results indicate towards automodification reaction strictly dependent represent a way control

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