The Inhibition of Hsp27 Chaperone Affects the Level of p53 Protein in Tumor Cells

E V Kaigorodova,L S Litvinova,L A Tashireva,E V Konovalova,O L Nosareva,M V Klimova,V V Novitskiy

doi:10.5539/ijb.v5n3p13

E V Kaigorodova, L S Litvinova + Show 5 more

Open Access

https://doi.org/10.5539/ijb.v5n3p13

Copy DOI

Abstract

The characteristics of p53 protein content in Jurkat and THP-1 tumor cell line, and mononuclear leukocytes were evaluated from in vitro studies with selective inhibition of the chaperone Hsp27. For the inhibition of Hsp27 KRIBB3 ((5-(5-ethyl-2-hydroxy-4-methoxyphenyl)-4-(4-methoxyphenyl)-isoxasole) was used. The p53 protein concentration was determined by Western blot analysis. The apoptoticly transformed cells with selective inhibitor Hsp27 were assessed by in vitro fluorescence microscopy using FITC-labeled annexin V and propidium iodide. The present study showed that the in vitro inhibition of the chaperone Hsp27 leads to an increase in p53 concentration in tumor cells and a growth of the amount of apoptotic cells in modified Jurkat and THP-1 cultures but revealed no such effects in the mononuclear leukocytes culture. Thus, Hsp27 appeared to play an important regulatory role in the activation of p53 protein of tumor cells.

Highlights

It is known that a cell incorporates different mechanisms that regulate the processes of survival and death
The present study showed that the in vitro inhibition of the chaperone Hsp27 leads to an increase in p53 concentration in tumor cells and a growth of the amount of apoptotic cells in modified Jurkat and THP-1 cultures but revealed no such effects in the mononuclear leukocytes culture
A higher concentration of p53 in tumor cells can be explained by the action of heat shock proteins, which are highly expressed in ontogenesis, perform the chaperone functions, stabilize and protect the mutant form of the transcription factor p53 from degradation

Summary

Introduction

It is known that a cell incorporates different mechanisms that regulate the processes of survival and death. The key transcription factor involved in the implementation of apoptosis is p53 This protein is activated in response to various forms of cellular stress and is essential for control of anti-proliferative processes. P53 can be induced by DNA damage, hypoxia, or aberrant expression of oncogenes This protein regulates DNA reparation, cellular senescence, and apoptosis (Levine, Hu, & Feng, 2006; Lin et al, 2004). Dysfunctions of p53 are accompanied by defects of the protection, genetic instability, cell immortality, which allows the damaged cells to survive and evolve (Beroud & Soussi, 2003) Taking these facts into account, it ts evident that p53 is the most frequently inactivated suppressor gene of carcinogenesis. In order to investigate the influence of Hsp on the general concentration of the transcription factor p53 in hematological cells and mononuclear leukocytes, obtained from healthy donors, the in vitro specific inhibition with KRIBB-3 was used

Methods

Results

Conclusion