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Sphingoid Base-Upregulated Caspase-14 Expression Involves MAPK.

Yukitoshi Nagahara1, Kei Kawakami1, Abudubari Sikandan1

  • 1Division of Life Science and Engineering, School of Science and Engineering, Tokyo Denki University.

Biological & Pharmaceutical Bulletin
|May 1, 2018
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Summary
This summary is machine-generated.

Sphingoid bases and ceramides, bioactive lipids, upregulate caspase-14 expression in skin cells. This process involves p38 and JNK signaling pathways, crucial for keratinocyte differentiation.

Keywords:
caspase-14keratinocytemitogen-activated protein kinasesphingoid base

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Area of Science:

  • Biochemistry
  • Dermatology
  • Cell Biology

Background:

  • Sphingolipids, including sphingoid bases and ceramides, are vital intracellular mediators.
  • Caspase-14 is predominantly expressed in skin's cornifying epithelia and is key to keratinocyte differentiation.
  • Ceramides, as key lipids in keratinocytes, are known to stimulate keratinocyte differentiation.

Purpose of the Study:

  • To investigate the role of sphingoid bases and ceramides in regulating caspase-14 expression.
  • To elucidate the signaling pathways involved in sphingoid base-induced caspase-14 upregulation.

Main Methods:

  • Treatment of human keratinocyte HaCaT cells with various sphingoid bases and C2-ceramide.
  • Analysis of caspase-14 mRNA and protein expression levels.
  • Utilizing specific inhibitors for mitogen-activated protein kinase pathways (p38 and JNK).
  • In vivo studies to confirm phytosphingosine effects.

Main Results:

  • Sphingosine, sphinganine, phytosphingosine, and C2-ceramide significantly increased caspase-14 mRNA and protein in a dose-dependent manner without causing cell damage.
  • Phytosphingosine-induced caspase-14 upregulation was blocked by p38 and JNK pathway inhibitors.
  • Phytosphingosine demonstrated caspase-14 upregulation in vivo.

Conclusions:

  • Sphingoid bases and ceramides effectively upregulate caspase-14 expression in keratinocytes.
  • The p38 and JNK signaling pathways are essential for phytosphingosine-mediated caspase-14 induction.
  • These findings suggest sphingoid bases contribute to keratinocyte differentiation via caspase-14 modulation.