[Dimethyl suberimidate as a specific inductor of apoptosis in transformed cells].
A modification of protein-protein interactions can be considered to be a way to regulate cell death. Chemical cross-linking agents have been traditionally used for protein complexing. This study has been undertaken to test a possibility to induce and(or) to modify cell death by a homobifunctional cross-linker dimethyl suberimidate (DMS). It was shown that the protein cross-linking by DMS resulted in a death of transformed cells by apoptosis. DMS-induced apoptosis was accompanied by cell cycle perturbations and down-regulation of p21/Waf1 mRNA expression. The RT-PCR analysis of bcl-2 family genes revealed the engagement of mitochondria in DMS-induced cytotoxicity. Then, the influence of DMS treatment on TNF-dependent and Fas-mediated apoptosis was investigated. Cell pre-incubation with DMS resulted in their increasing sensitivity for the TNF cytotoxic effect, though activities of anti-Fas cytotoxic antibodies were inhibited. The effects observed are probably due to cross-linking of TNF-receptors. Thus, this study first demonstrated that a chemical cross-linker DMS in capable of inducing apoptosis in transformed cells and modifying TNF-dependent and Fas-mediated apoptosis.
Moshnikova
A B
AB
Institute of Theoretical and Experimental Biophysics RAS, Pushchino.
Moshnikov
S A
SA
Afanas'ev
V N
VN
Krotova
K E
KE
Sadovnikov
V B
VB
Beletskiĭ
I P
IP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002461:Cell Line, Transformed; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000187:drug effects / Q000235:genetics; D004120:Dimethyl Suberimidate / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D019254:Genes, bcl-2 / Q000187:drug effects; D006801:Humans; D051379:Mice; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019014:fas Receptor / Q000235:genetics
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D003432:Cross-Linking Reagents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D004120:Dimethyl Suberimidate
Dimetilsuberimidat kak spetsificheskiĭ induktor apoptoza transformirovannykh kletochnykh kul'tur.