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1,25-Dihydroxyvitamin D3 induces biphasic NF-[kappa]B responses during HL-60 leukemia cells differentiation through protein induction and PI3K/Akt-dependent phosphorylation/degradation of I[kappa]B

Tse, Anfernee Kai-Wing ; Chi-Keung, Wan ; Xiao-Ling, Shen ; Guo-Yuan, Zhu ; Hon-Yeung, Cheung ; Yang, Mengsu ; Wang-Fun, Fong

Experimental cell research, 2007-05, Vol.313 (8), p.1722 [Periódico revisado por pares]

New York: Elsevier BV

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  • Título:
    1,25-Dihydroxyvitamin D3 induces biphasic NF-[kappa]B responses during HL-60 leukemia cells differentiation through protein induction and PI3K/Akt-dependent phosphorylation/degradation of I[kappa]B
  • Autor: Tse, Anfernee Kai-Wing ; Chi-Keung, Wan ; Xiao-Ling, Shen ; Guo-Yuan, Zhu ; Hon-Yeung, Cheung ; Yang, Mengsu ; Wang-Fun, Fong
  • Assuntos: Cellular biology ; Leukemia ; Molecular biology ; Proteins
  • É parte de: Experimental cell research, 2007-05, Vol.313 (8), p.1722
  • Descrição: 1,25-Dihydroxyvitamin D3 (VD3) induces differentiation in a number of leukemia cell lines and under various conditions is able to either stimulate or inhibit nuclear factor kappa B (NF-kappaB) activity. Here we report a time-dependent biphasic regulation of NF-kappaB in VD3-treated HL-60 leukemia cells. After VD3 treatment there was an early approximately 4 h suppression and a late 8-72 h prolonged reactivation of NF-kappaB. The reactivation of NF-kappaB was concomitant with increased IKK activities, IKK-mediated IkappaBalpha phosphorylation, p65 phosphorylation at residues S276 and S536, p65 nuclear translocation and p65 recruitment to the NF-kappaB/vitamin D responsive element promoters. In parallel with NF-kappaB stimulation, there was an up-regulation of NF-kappaB controlled inflammatory and anti-apoptotic genes such as TNFalpha, IL-1beta and Bcl-xL. VD3-triggered reactivation of NF-kappaB was associated with PI3K/Akt phosphorylation. PI3K/Akt antagonists suppressed VD3-stimulated IkappaBalpha phosphorylation as well as NF-kappaB-controlled gene expression. The early approximately 4 h VD3-mediated NF-kappaB suppression coincided with a prolonged increase of IkappaBalpha protein which require de novo protein synthesis, lasted for as least 72 h and was insensitive to MAPK, IKK or PI3K/Akt inhibitors. Our data suggest a novel biphasic regulation of NF-kappaB in VD3-treated leukemia cells and our results may have provided the first molecular explanation for the contradictory observations reported on VD3-mediated immune-regulation. [PUBLICATION ABSTRACT]
  • Editor: New York: Elsevier BV
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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