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HSPA2 overexpression protects V79 fibroblasts against bortezomib-induced apoptosis
Piotr Teodor Filipczak1, Wojciech Piglowski, Magdalena Glowala-Kosinska
1Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
Abstract:
Human HSPA2 is a member of the HSPA (HSP70) family of heat-shock proteins, encoded by the gene originally described as testis-specific. Recently, it has been reported that HSPA2 can be also expressed in human somatic tissues in a cell-type specific manner. The aim of the present study was to find out whether HSPA2 can increase the resistance of somatic cells to the toxic effect of heat shock, proteasome inhibitors, and several anticancer cytostatics. We used a Chinese hamster fibroblast V79 cell line because these cells do not express the HSPA2 and cytoprotective HSPA1 proteins under normal culture conditions and show limited ability to express HSPA1 in response to heat shock and proteasome inhibitors. We established, by retroviral gene transfer, a stable V79/HSPA2 cell line, which constitutively overexpressed HSPA2 protein. The major observation of our study was that HSPA2 increased long-term survival of cells subjected to heat shock and proteasome inhibitors. We found, that HSPA2 confers resistance to bortezomib-induced apoptosis. Thus, we showed for the first time that in somatic cells HSPA2 can be a part of a system protecting cells against cytotoxic stimuli inducing proteotoxic stress.
Insights
Human heat shock protein A2 (HSPA2) enhances somatic cell survival against heat shock and proteasome inhibitors. This study demonstrates HSPA2
Area of Science:
- Molecular Biology
- Cell Biology
- Stress Response
Background:
- Human heat shock protein A2 (HSPA2), part of the HSP70 family, was initially identified as testis-specific.
- Recent findings indicate HSPA2 expression in specific human somatic tissues.
- The cytoprotective roles of HSPA2 in somatic cells remain largely unexplored.
Purpose of the Study:
- To investigate whether HSPA2 enhances somatic cell resistance to heat shock, proteasome inhibitors, and anticancer drugs.
- To determine if HSPA2 confers protection against proteotoxic stress in non-testicular cells.
Main Methods:
- Established a stable Chinese hamster fibroblast V79 cell line overexpressing HSPA2 via retroviral gene transfer.
- Utilized a V79 cell line deficient in endogenous HSPA2 and with limited HSPA1 inducibility.
- Assessed cell survival following exposure to heat shock, proteasome inhibitors (e.g., bortezomib), and cytostatics.
Main Results:
- Overexpression of HSPA2 significantly increased long-term survival of V79 cells under heat shock conditions.
- HSPA2 conferred substantial resistance to cell death induced by proteasome inhibitors, including bortezomib.
- Demonstrated HSPA2's role in protecting somatic cells from bortezomib-induced apoptosis.
Conclusions:
- HSPA2 confers significant cytoprotection to somatic cells against proteotoxic stress.
- HSPA2 plays a crucial role in enhancing cell survival under conditions of heat shock and proteasome inhibition.
- This study provides the first evidence of HSPA2's protective function in somatic cells against cytotoxic stimuli.
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