Sodium butyrate induced keratinocyte apoptosis |
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Authors: | Ilse S Daehn Antiopi Varelias Timothy E Rayner |
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Institution: | (1) Child Health Research Institute, Women's and Children's Hospital, North Adelaide, SA, Australia;(2) Department of Surgery, The Queen Elizabeth Hospital, The University of Adelaide, Woodville, SA, Australia;(3) Department of Medical Biotechnology, The Flinders University of South Australia, Bedford Park, SA, Australia |
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Abstract: | Apoptosis of keratinocytes is a key mechanism required for epidermal homeostasis and the renewal of damaged cells. Its dysregulation
has been implicated in many skin diseases including cancer and hyperproliferative disorders. In the present study, the effect
of sodium butyrate, a histone deacetylase inhibitor, on keratinocyte apoptosis was investigated using the HaCaT human keratinocyte
cell line. Sodium butyrate induced morphological changes associated with apoptosis and nuclear fragmentation of HaCaTs. Annexin
V staining demonstrated that sodium butyrate induced apoptosis in a dose and time-dependent manner with 50% of HaCaTs apoptotic
after exposure to 0.8 mg/ml sodium butyrate for 24 h. Apoptosis was associated with upregulation of cell surface expression
of the death receptor Fas and activation of the extrinsic caspase pathway, with induction of caspase 8 activity peaking after
8 h. Caspase 3 activity peaked after 24 h and was associated with cleavage of the caspase 3 substrate, poly (ADP-ribose) polymerase
(PARP). The intrinsic caspase pathway was not activated as caspase 9 activity was not detected, and there was no change in
the expression of terminal differentiation markers keratin 10 and involucrin following sodium butyrate treatment. Together
these results indicate that sodium butyrate is a potent inducer of Fas associated apoptosis via caspase activation in HaCaT
keratinocytes, an effect that is independent of the induction of terminal differentiation. |
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Keywords: | Apoptosis Caspase Fas Keratinocyte Sodium butyrate |
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