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Aleksandra Wojtala

Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)

Recent publications
1.  Malińska D., Szymański J., Patalas-Krawczyk P., Michalska B., Wojtala A., Prill M., Partyka M., Drabik K., Walczak J., Sewer A., Johne S., Luettich K., Peitsch M.C., Hoeng J., Duszyński J., Szczepanowska J., van der Toorn M., Więckowski M.R., Assessment of mitochondrial function following short- and long-term exposure of human bronchial epithelial cells to total particulate matter from a candidate modified-risk tobacco product and reference cigarettes, Food and Chemical Toxicology, ISSN: 0278-6915, DOI: 10.1016/j.fct.2018.02.013, Vol.115, pp.1-12, 2018

Abstract:
Mitochondrial dysfunction caused by cigarette smoke is involved in the oxidative stress-induced pathology of airway diseases. Reducing the levels of harmful and potentially harmful constituents by heating rather than combusting tobacco may reduce mitochondrial changes that contribute to oxidative stress and cell damage. We evaluated mitochondrial function and oxidative stress in human bronchial epithelial cells (BEAS 2B) following 1- and 12-week exposures to total particulate matter (TPM) from the aerosol of a candidate modified-risk tobacco product, the Tobacco Heating System 2.2 (THS2.2), in comparison with TPM from the 3R4F reference cigarette. After 1-week exposure, 3R4F TPM had a strong inhibitory effect on mitochondrial basal and maximal oxygen consumption rates compared to TPM from THS2.2. Alterations in oxidative phosphorylation were accompanied by increased mitochondrial superoxide levels and increased levels of oxidatively damaged proteins in cells exposed to 7.5 μg/mL of 3R4F TPM or 150 μg/mL of THS2.2 TPM, while cytosolic levels of reactive oxygen species were not affected. In contrast, the 12-week exposure indicated adaptation of BEAS-2B cells to long-term stress. Together, the findings indicate that 3R4F TPM had a stronger effect on oxidative phosphorylation, gene expression and proteins involved in oxidative stress than TPM from the candidate modified-risk tobacco product THS2.2.

Keywords:
Mitochondria, Mitochondrial respiratory chain, Oxidative stress, BEAS-2B cells, Cigarette, Tobacco heating system

Affiliations:
Malińska D. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Szymański J. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Patalas-Krawczyk P. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Michalska B. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Wojtala A. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Prill M. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Partyka M. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Drabik K. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Walczak J. - other affiliation
Sewer A. - Philip Morris Products S.A. (CH)
Johne S. - Philip Morris Products S.A. (CH)
Luettich K. - Philip Morris Products S.A. (CH)
Peitsch M.C. - Philip Morris Products S.A. (CH)
Hoeng J. - Philip Morris Products S.A. (CH)
Duszyński J. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Szczepanowska J. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
van der Toorn M. - Philip Morris Products S.A. (CH)
Więckowski M.R. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
2.  Alster O., Bielak-Żmijewska A., Mosieniak G., Moreno-Villaneuva M., Dudka-Ruszkowska W., Wojtala A., Kusio-Kobiałka M., Korwek Z., Burkle A., Piwocka K., Siwicki J.K., Sikora E., The Role of Nibrin in Doxorubicin-Induced Apoptosis and Cell Senescence in Nijmegen Breakage Syndrome Patients Lymphocytes, PLOS ONE, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0104964, Vol.9, No.8, pp.e104964-1-13, 2014

Abstract:
Nibrin plays an important role in the DNA damage response (DDR) and DNA repair. DDR is a crucial signaling pathway in apoptosis and senescence. To verify whether truncated nibrin (p70), causing Nijmegen Breakage Syndrome (NBS), is involved in DDR and cell fate upon DNA damage, we used two (S4 and S3R) spontaneously immortalized T cell lines from NBS patients, with the founding mutation and a control cell line (L5). S4 and S3R cells have the same level of p70 nibrin, however p70 from S4 cells was able to form more complexes with ATM and BRCA1. Doxorubicin-induced DDR followed by cell senescence could only be observed in L5 and S4 cells, but not in the S3R ones. Furthermore the S3R cells only underwent cell death, but not senescence after doxorubicin treatment. In contrary to doxorubicin treatment, cells from all three cell lines were able to activate the DDR pathway after being exposed to γ-radiation. Downregulation of nibrin in normal human vascular smooth muscle cells (VSMCs) did not prevent the activation of DDR and induction of senescence. Our results indicate that a substantially reduced level of nibrin or its truncated p70 form is sufficient to induce DNA-damage dependent senescence in VSMCs and S4 cells, respectively. In doxorubicin-treated S3R cells DDR activation was severely impaired, thus preventing the induction of senescence.

Affiliations:
Alster O. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Bielak-Żmijewska A. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Mosieniak G. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Moreno-Villaneuva M. - University of Konstanz (DE)
Dudka-Ruszkowska W. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Wojtala A. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Kusio-Kobiałka M. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Korwek Z. - other affiliation
Burkle A. - University of Konstanz (DE)
Piwocka K. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)
Siwicki J.K. - Institute of Oncology (PL)
Sikora E. - Nencki Institute of Experimental Biology, Polish Academy of Sciences (PL)

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