TY - JOUR
T1 - Molecular basis for premature senescence induced by surfactants in normal human cells
AU - Yamakami, Yoshimi
AU - Miki, Kensuke
AU - Yonekura, Ryuzo
AU - Kudo, Ikuru
AU - Fujii, Michihiko
AU - Ayusawa, Dai
N1 - Publisher Copyright:
© 2014 Japan Society for Bioscience Biotechnology and Agrochemistry.
Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 2014
Y1 - 2014
N2 - Sublethal doses of surfactants as exemplified by NP-40 clearly induce premature senescence in normal human cells. To understand molecular basis for this phenomenon, we tried to suppress it with use of various inhibitors. An inhibitor of p38 of the MAPK family almost completely suppressed growth arrest and morphological changes induced by surfactants; however, other inhibitors tested had no effect. Oleic acid, a weak inducer of premature senescence, was found to suppress the effect of NP-40. Fluoresceinlabeled oleic acid rapidly bound to the cell surface, and this binding was clearly blocked by pre-treatment with surfactants, suggesting that surfactants and oleic acid compete for binding to the cell surface. Moderate concentrations of cycloheximide, an inhibitor of protein synthesis, also suppressed the senescent features induced by NP-40. These results suggest that surfactants activate p38 signaling pathway by binding to the cell surface, and induce cellular senescence.
AB - Sublethal doses of surfactants as exemplified by NP-40 clearly induce premature senescence in normal human cells. To understand molecular basis for this phenomenon, we tried to suppress it with use of various inhibitors. An inhibitor of p38 of the MAPK family almost completely suppressed growth arrest and morphological changes induced by surfactants; however, other inhibitors tested had no effect. Oleic acid, a weak inducer of premature senescence, was found to suppress the effect of NP-40. Fluoresceinlabeled oleic acid rapidly bound to the cell surface, and this binding was clearly blocked by pre-treatment with surfactants, suggesting that surfactants and oleic acid compete for binding to the cell surface. Moderate concentrations of cycloheximide, an inhibitor of protein synthesis, also suppressed the senescent features induced by NP-40. These results suggest that surfactants activate p38 signaling pathway by binding to the cell surface, and induce cellular senescence.
KW - Cellular senescence
KW - Oleic acid
KW - P38
KW - Surfactant
KW - Unbalanced growth
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U2 - 10.1080/09168451.2014.946391
DO - 10.1080/09168451.2014.946391
M3 - Article
C2 - 25198914
AN - SCOPUS:84924530911
VL - 78
SP - 2022
EP - 2029
JO - Bioscience, Biotechnology and Biochemistry
JF - Bioscience, Biotechnology and Biochemistry
SN - 0916-8451
IS - 12
ER -