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Isoproterenol accelerates apoptosis through the over-expression of the sodium/calcium exchanger in HeLa cells

Authors :
Olga Krizanova
Marcela Laukova
Jan Sedlak
Viera Bohacova
Sona Hudecova
Lubomira Lencesova
Lucia Csaderova
Source :
General physiology and biophysics. 32:311-323
Publication Year :
2014
Publisher :
AEPress, s.r.o., 2014.

Abstract

Apoptosis induction causes over-expression of the Na + /Ca 2+ exchanger of type 1 (NCX1) in the HeLa cell line. During induction of apoptosis and in the presence of isoproterenol hydrochlo- ride (I; β-adrenergic agonist), increase in the NCX1 is even more pronounced. Anti-apoptotic Bcl-2 mRNA and protein is markedly reduced during apoptosis and in the presence of I, which causes a rapid increase in the Bax/Bcl-2 ratio. During apoptosis induction by apoptosis inducing kit (A), both with and without I, the active form of caspase-3, which is the executive enzyme in apoptosis, becomes visible on Western blots. Silencing NCX1 resulted in the reversal of the Bax/Bcl-2 ratio, it prevented a decrease in mitochondrial membrane potential compared to the AI group and it decreased the level of AI-induced apoptosis in HeLa cells. Based on the experiments with single apoptotic inducers camptothecin, cycloheximide and dexamethasone, it might be proposed that potentiated apoptotic effect in I-treated cells is due to the inhibition of nuclear topoisomerase. As illustrated in immunofluorescence and Western blot analysis, calnexin increased significantly during induction of the apoptosis in the presence of I. In addition, further decrease in sarco/endoplasmic ATPase 2 (SERCA2), decrease in reticular calcium and mitochondrial membrane potential was observed, which suggests development of the endoplasmic reticulum (ER) stress. Based on these results, we propose that I further enhanced NCX1 expression in apoptotic cells through the development of ER stress.

Details

ISSN :
13384325
Volume :
32
Database :
OpenAIRE
Journal :
General physiology and biophysics
Accession number :
edsair.doi.dedup.....0c8d939965e1892eb71e58f89c66b257
Full Text :
https://doi.org/10.4149/gpb_2013044