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• W2048232436 endingPage "4788" @default.
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• W2048232436 abstract "Side-chain modified vitamin D analogs including 20-Epi-22-oxa-24a,26a,27a-trihomo-1α,25-dihydroxyvitamin D3 (KH1060), and 1,24-dihydroxy-22-ene-24-cyclopropyl-vitamin D3 (MC903) were originally designed to aid in the treatment of hyperproliferative disorders including psoriasis and cancer. Here we demonstrate that these analogs, as well as the 6-cis-locked conformer, 1α,25-dihydroxy-lumisterol3 (JN) prime NB4 cells for monocytic differentiation. Previously, the action of MC903 and KH1060 was presumed to be mediated by the nuclear vitamin D receptor (VDRnuc). Differentiation in response to all analogs was shown to be inhibited by 1β,25-dihydroxyvitamin D3 (HL), the antagonist to the nongenomic activities of 1,25D3. These data suggest that although MC903 and KH1060 may bind the VDRnuc, that the differentiative activities of these agents requires nongenomic signaling pathways. Here we show that 1α,25(OH)2-d5-previtamin D3 (HF), JN, KH1060, and MC903 induce expression of PKCα and PKCδ and translocation of both isoforms to the particulate fraction, and PKCα to the nuclear fraction. The full differentiation response with combinations of analogs and TPA was inhibited 50% by the mem-brane permeable Ca2+ chelator, 1,2-bis(o-aminophenoxy)-ethane-N,N,N′,N′-tetraacetic acid (BAPTA-AM) or calpain inhibitor I. These data demonstrate that intracellular free calcium and the calcium-dependent protease, calpain play critical roles in monocytic differentiation. Intracellular calcium appears to be most critical in the 1,25D3-priming stage of differentiation, while calpain is essential in the TPA maturation response." @default.
• W2048232436 created "2016-06-24" @default.
• W2048232436 creator A5002790076 @default.
• W2048232436 creator A5079657671 @default.
• W2048232436 date "1999-10-01" @default.
• W2048232436 modified "2023-10-13" @default.
• W2048232436 title "Vitamin D Analogs, 20-Epi-22-Oxa-24a,26a,27a,-Trihomo-1α,25(OH)2-Vitamin D3, 1,24(OH)2-22-Ene-24-Cyclopropyl-Vitamin D3 and 1α,25(OH)2-Lumisterol3 Prime NB4 Leukemia Cells for Monocytic Differentiation via Nongenomic Signaling Pathways, Involving Calcium and Calpain1" @default.
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• W2048232436 doi "https://doi.org/10.1210/endo.140.10.7041" @default.
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• W2048232436 hasPublicationYear "1999" @default.
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