Molecular basis for premature senescence induced by surfactants in normal human cells
Yoshimi Yamakami1, Kensuke Miki, Ryuzo Yonekura
1a Graduate School of Nanobioscience , Yokohama City University , Yokohama , Japan.
Abstract:
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. Fluorescein-labeled 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.
Insights
Surfactants like NP-40 trigger premature cell aging in human cells by activating the p38 MAPK pathway. This process can be blocked by oleic acid, suggesting a competitive binding mechanism at the cell surface.
Area of Science:
- Cell Biology
- Molecular Biology
- Toxicology
Background:
- Surfactants are widely used in research and industry.
- Sublethal doses of certain surfactants can induce cellular stress responses.
- Premature senescence is a cellular state characterized by irreversible growth arrest.
Purpose of the Study:
- To elucidate the molecular mechanisms by which surfactants induce premature senescence.
- To identify key signaling pathways involved in surfactant-induced senescence.
- To investigate potential suppressors of surfactant-induced senescence.
Main Methods:
- Treatment of normal human cells with sublethal doses of NP-40 surfactant.
- Utilizing various chemical inhibitors to block specific signaling pathways.
- Employing oleic acid as a potential suppressor and investigating its binding characteristics.
- Assessing cellular senescence through growth arrest and morphological changes.
Main Results:
- NP-40 induced premature senescence, including growth arrest and morphological changes.
- Inhibition of the p38 mitogen-activated protein kinase (MAPK) pathway significantly suppressed NP-40-induced senescence.
- Oleic acid, a weak inducer of senescence, suppressed NP-40 effects and competed for cell surface binding.
- Cycloheximide partially suppressed surfactant-induced senescent features.
Conclusions:
- Surfactants activate the p38 MAPK signaling pathway, leading to premature cellular senescence.
- Cell surface interactions are critical for surfactant-induced senescence, as indicated by competition with oleic acid.
- The p38 MAPK pathway is a key mediator of surfactant-induced cellular aging.
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