Nonylphenol and octylphenol-induced apoptosis in human embryonic stem cells is related to Fas-Fas ligand pathway

Suel Kee Kim, Byung Kak Kim, Joong Hyun Shim, Jung Eun Gil, Yong Dal Yoon, Jong-Hoon Kim

Research output: Contribution to journalArticle

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Abstract

Human embryonic stem (hES) cells have been proposed as a source of various cell types for cell replacement therapy. Besides their potential in therapeutic uses, ES cells also have other potential applications, such as in drug discovery and in vitro screening assays of various toxicants. Nonylphenol (NP) and octylphenol (OP) are common environmental contaminants, known to disrupt the reproductive and endocrine system. However, little is known about their toxicological effects on early embryonic development in humans. In this study, we used undifferentiated hES cells and the neural progenitor cells derived from them to investigate the potential toxicity of NP and OP. Our results show that the cytotoxic effects of NP and OP involve DNA fragmentation, the major characteristic of apoptosis. The NP- and OP-induced apoptosis was concomitant with the increased activity of Caspase-8 and -3. Moreover, both Fas and Fas ligand (FasL) protein expressions were markedly increased in the NP- or OP-exposed hES cells. These results suggest that NP and OP are able to trigger apoptosis in hES cells via a pathway dependent on caspase activation and Fas-FasL interaction. In particular, hES cell-derived neural progenitor cells had a higher sensitivity to the toxicants than undifferentiated hES cells, thereby suggesting that the toxic stress response may differ depending on the developmental stage. These findings offer new perspectives for understanding the fundamental mechanisms in chemical-induced apoptosis in hES cells.

Original languageEnglish
Pages (from-to)310-321
Number of pages12
JournalToxicological Sciences
Volume94
Issue number2
DOIs
Publication statusPublished - 2006 Dec 1

Fingerprint

Fas Ligand Protein
Stem cells
Apoptosis
Stem Cells
Endocrine System
Caspase 8
Poisons
Therapeutic Uses
DNA Fragmentation
Drug Discovery
Cell- and Tissue-Based Therapy
Caspases
octylphenol
nonylphenol
Human Embryonic Stem Cells
Caspase 3
Toxicology
Embryonic Development
Toxicity
Assays

Keywords

  • Apoptosis
  • Caspase
  • Fas-Fas ligand pathway
  • Human embryonic stem cell
  • Nonylphenol
  • Octylphenol

ASJC Scopus subject areas

  • Toxicology

Cite this

Nonylphenol and octylphenol-induced apoptosis in human embryonic stem cells is related to Fas-Fas ligand pathway. / Kim, Suel Kee; Kim, Byung Kak; Shim, Joong Hyun; Gil, Jung Eun; Yoon, Yong Dal; Kim, Jong-Hoon.

In: Toxicological Sciences, Vol. 94, No. 2, 01.12.2006, p. 310-321.

Research output: Contribution to journalArticle

Kim, Suel Kee ; Kim, Byung Kak ; Shim, Joong Hyun ; Gil, Jung Eun ; Yoon, Yong Dal ; Kim, Jong-Hoon. / Nonylphenol and octylphenol-induced apoptosis in human embryonic stem cells is related to Fas-Fas ligand pathway. In: Toxicological Sciences. 2006 ; Vol. 94, No. 2. pp. 310-321.
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