engleski

Hydrogen peroxide-induced oxidative stress increases expression of p53 and p73 proteins in neuroblastoma SH-SY5Y cells

Many approaches in tumour therapy are based on the oxidative stress-induced apoptosis by using radiotherapy or chemotherapeutics. The aim of the present study was to examine the effect of hydrogen peroxide (H2O2)-provoked oxidative stress on the expression of tumour suppressor proteins p53 and p73 in the neuroblastoma cell line SH- SY5Y. Both proteins are involved in the initiation of apoptosis and are present in cells in various isoforms whose dynamic changes may contribute to apoptotic response. In a concentration-dependent manner H2O2 decreased cell survival, intracellular glutathione and ATP levels, and increased accumulation of reactive oxygen species and caspase-3/7 activity. Western blot method revealed an enhancement in the expression of the total p53 protein and its isoform p53α by using antibodies SAPU, DO-11 and DO-12. Protein detection with KJC8 antibody that recognises all β-isoforms of p53 protein indicated reduced expression of isoforms p53β and Δ40p53β in p53-mediated cell death. H2O2 also triggered strong induction of p73 expression, particularly the TAp73α isoform. The obtained results suggest that increased expressions of p53 and p73 proteins greatly contribute to reduced survival of SH-SY5Y cells under oxidative stress conditions. Although further investigations are required to more clearly identify contribution of specific p53 and p73 isoforms to the initiation of death cascade, it seems that certain isoforms may be promising candidates as novel therapeutic targets in the anti-cancer therapy.

SH-SY5Y neuroblastoma cell line ; Oxidative stress ; p53 and p73 proteins ; Apoptosis

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