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Title: Protective role of klotho protein on epithelial cells upon co-culture with activated or senescent monocytes

Abstract

Monocytes ensure proper functioning and maintenance of epithelial cells, while good condition of monocytes is a key factor of these interactions. Although, it was shown that in some circumstances, a population of altered monocytes may appear, there is no data regarding their effect on epithelial cells. In this study, using direct co-culture model with LPS-activated and Dox-induced senescent THP-1 monocytes, we reported for the first time ROS-induced DNA damage, reduced metabolic activity, proliferation inhibition and cell cycle arrest followed by p16-, p21- and p27-mediated DNA damage response pathways activation, premature senescence and apoptosis induction in HeLa cells. Also, we show that klotho protein possessing anti-aging and anti-inflammatory characteristics reduced cytotoxic and genotoxic events by inhibition of insulin/IGF-IR and downregulation of TRF1 and TRF2 proteins. Therefore, klotho protein could be considered as a protective factor against changes caused by altered monocytes in epithelial cells. - Highlights: • Activated and senescent THP-1 monocytes induced cyto- and genotoxicity in HeLa cells. • Altered monocytes provoked oxidative and nitrosative stress-induced DNA damage. • DNA damage activated DDR pathways and lead to premature senescence and apoptosis. • Klotho reduced ROS/RNS-mediated toxicity through insulin/IGF-IR pathway inhibition. • Klotho protects HeLa cells from cyto- and genotoxicity inducedmore » by altered monocytes.« less

Authors:
 [1];  [2]; ; ;  [1];  [2]
  1. Institute of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa (Poland)
  2. (Poland)
Publication Date:
OSTI Identifier:
22649816
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 350; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AGING; APOPTOSIS; CELL CYCLE; DNA; DNA DAMAGES; HELA CELLS; INFLAMMATION; INHIBITION; INSULIN; LEAD; MONOCLINIC LATTICES; MONOCYTES; OXIDATION; PHOSPHORUS 21; PHOSPHORUS 27; TOXICITY

Citation Formats

Mytych, Jennifer, E-mail: jennifermytych@gmail.com, Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Wos, Izabela, Solek, Przemyslaw, Koziorowski, Marek, and Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa. Protective role of klotho protein on epithelial cells upon co-culture with activated or senescent monocytes. United States: N. p., 2017. Web. doi:10.1016/J.YEXCR.2016.12.013.
Mytych, Jennifer, E-mail: jennifermytych@gmail.com, Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Wos, Izabela, Solek, Przemyslaw, Koziorowski, Marek, & Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa. Protective role of klotho protein on epithelial cells upon co-culture with activated or senescent monocytes. United States. doi:10.1016/J.YEXCR.2016.12.013.
Mytych, Jennifer, E-mail: jennifermytych@gmail.com, Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Wos, Izabela, Solek, Przemyslaw, Koziorowski, Marek, and Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa. Sun . "Protective role of klotho protein on epithelial cells upon co-culture with activated or senescent monocytes". United States. doi:10.1016/J.YEXCR.2016.12.013.
@article{osti_22649816,
title = {Protective role of klotho protein on epithelial cells upon co-culture with activated or senescent monocytes},
author = {Mytych, Jennifer, E-mail: jennifermytych@gmail.com and Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa and Wos, Izabela and Solek, Przemyslaw and Koziorowski, Marek and Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa},
abstractNote = {Monocytes ensure proper functioning and maintenance of epithelial cells, while good condition of monocytes is a key factor of these interactions. Although, it was shown that in some circumstances, a population of altered monocytes may appear, there is no data regarding their effect on epithelial cells. In this study, using direct co-culture model with LPS-activated and Dox-induced senescent THP-1 monocytes, we reported for the first time ROS-induced DNA damage, reduced metabolic activity, proliferation inhibition and cell cycle arrest followed by p16-, p21- and p27-mediated DNA damage response pathways activation, premature senescence and apoptosis induction in HeLa cells. Also, we show that klotho protein possessing anti-aging and anti-inflammatory characteristics reduced cytotoxic and genotoxic events by inhibition of insulin/IGF-IR and downregulation of TRF1 and TRF2 proteins. Therefore, klotho protein could be considered as a protective factor against changes caused by altered monocytes in epithelial cells. - Highlights: • Activated and senescent THP-1 monocytes induced cyto- and genotoxicity in HeLa cells. • Altered monocytes provoked oxidative and nitrosative stress-induced DNA damage. • DNA damage activated DDR pathways and lead to premature senescence and apoptosis. • Klotho reduced ROS/RNS-mediated toxicity through insulin/IGF-IR pathway inhibition. • Klotho protects HeLa cells from cyto- and genotoxicity induced by altered monocytes.},
doi = {10.1016/J.YEXCR.2016.12.013},
journal = {Experimental Cell Research},
number = 2,
volume = 350,
place = {United States},
year = {Sun Jan 15 00:00:00 EST 2017},
month = {Sun Jan 15 00:00:00 EST 2017}
}