Hsp72 controls bortezomib-induced HepG2 cell death via interaction with pro-apoptotic factors.
The proteasome inhibitor bortezomib is an efficacious inducer of apoptosis in the hepatoma HepG2 cell line. This study shows that bortezomib increased in these cells the level of the survival factor Hsp72 in a time- and dose-dependent manner. In a first phase of treatment, Hsp72 rapidly increased so that at 24 h of incubation with 50 nM bortezomib its level was approximately five-fold higher than the control. In this phase Hsp72 seemed to play a role in preventing HepG2 cell death, since it interacted with and sequestered the pro-apoptotic factors p53, AIF, Bax and Apaf-1. During a second day of treatment, although the nuclear levels of Hsp72, p53 and AIF increased, the interaction of Hsp72 with these factors diminished. In addition, bortezomib induced the activation of caspases, which stimulated Hsp72 degradation. In conclusion, in the second day of treatment with bortezomib the protective ability of Hsp72 decreased thus favouring the appearance of apoptosis.
Calvaruso
Giuseppe
G
Dipartimento di Scienze Biochimiche, Università degli Studi di Palermo, 90127 Palermo, Italy.
Giuliano
Michela
M
Portanova
Patrizia
P
Pellerito
Ornella
O
Vento
Renza
R
Tesoriere
Giovanni
G
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D047468:Immunoprecipitation; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology; D011485:Protein Binding; D011719:Pyrazines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
C494829:AIFM1 protein, human; C506592:APAF1 protein, human; D000590:Amino Acid Chloromethyl Ketones; D051033:Apoptosis Inducing Factor; D051017:Apoptosis Regulatory Proteins; D053477:Apoptotic Protease-Activating Factor 1; C494826:BAX protein, human; D001897:Boronic Acids; D050884:HSP72 Heat-Shock Proteins; D011480:Protease Inhibitors; D011719:Pyrazines; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D000069286:Bortezomib