Proteomics demonstration that histone H4 is a colchicine-induced retro-modulator of growth and alkaline phosphatase activity in hair follicle dermal papilla culture

Ching Wu Hsia, Hao Ai Shui, Chih Yuan Wang, Hui Ming Yu, Ming Yi Ho, Kur Ta Cheng, Min Jen Tseng

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Dermal papilla cells (DPCs) control the development of hair follicles via cell-cell interactions and extracellular molecules. Colchicine affected active anagen DPCs to result in hair loss in the clinical setting. The purpose of this study was to identify the retro-modulator released by DPCs exposed to sub-toxic dose of colchicine and elucidate its effect on dermal papilla culture. The molecular-weight cutoff ultrafiltration and HPLC were used to purify the components of colchicine-treated DPC secretomes and examined their ability to down-regulate the growth and alkaline phosphatase (ALP) activity of DPCs. The active product was identified by in-gel trypsin digestion, nano-LC-ESI-MS/MS and validated by Western blot to be histone H4 (P62804), which inhibited the proliferation and diminished the ALP activity of cultured DPCs. Treating DPCs with recombinant histone H4 reproduced the growth inhibition effect whereas adding antibody to immunoneutralize histone H4 abolished this growth inhibitory consequence. DPCs with high ALP activity can induce the neogenesis of hair follicles and support the hair fiber growth in vivo. Our results indicated that sub-lethal colchicine can inactivate DPCs through releasing histone H4. Through the investigation of the retro-modulation of histone H4 on dermal papillae may give implications for understanding the mechanism of colchicine-induced hair disorder.

Original languageEnglish
Pages (from-to)805-816
Number of pages12
JournalJournal of Proteomics
Volume74
Issue number6
DOIs
Publication statusPublished - May 16 2011

Keywords

  • Alopecia
  • Colchicine
  • Conditioned medium
  • Dermal papilla cell
  • Histone H4
  • Secretome

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

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