Expression pattern of Nav2 in the murine CNS with development.

Neuron navigator 2 (NAV2, RAINB1, POMFIL2, HELAD1, unc53H2) is essential for nervous system development. In the present study the spatial distribution of Nav2 transcript in mouse CNS during embryonic, postnatal and adult life is examined. Because multiple NAV2 proteins are predicted based on alternate promoter usage and RNA splicing, in situ hybridization was performed using probes designed to the 5' and 3' ends of the Nav2 transcript, and PCR products using primer sets spanning the length of the mRNA were also examined by real time PCR (qPCR).

Differential activity of 2-methylene-19-nor vitamin D analogs on growth factor gene expression in rhino mouse skin and comparison to all-trans retinoic acid.

While all 2-methylene-19-nor analogs of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) tested produce an increase in epidermal thickness in the rhino mouse, only a subset reduce utricle size (comedolysis). All-trans retinoic acid (atRA) also causes epidermal thickening and a reduction in utricle size in the rhino mouse. We now report that 2-methylene-19-nor-(20S)-1α-hydroxybishomopregnacalciferol (2MbisP), a comedolytic analog, increases epidermal thickening more rapidly than does atRA, while both reduce utricle area at an equal rate.

Identification of a unique subset of 2-methylene-19-nor analogs of vitamin D with comedolytic activity in the rhino mouse.

The active metabolite of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), and a series of 2-methylene-19-nor analogs of 1,25(OH)(2)D(3) were evaluated for their ability to reduce the size of utricles (comedolytic activity) in a rhino mouse model of acne. All analogs tested, as well as the native hormone, increased the skin epidermal thickness. In contrast, only a subset of analogs that lacked a full side chain and 25-hydroxyl group were found to possess comedolytic activity.

2-Methylene-19-nor-1alpha-hydroxyvitamin D3 analogs inhibit adipocyte differentiation and PPARgamma2 gene transcription.

The hormonally active form of vitamin D3, 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), prevents adipogenesis in the 3T3-L1 preadipocyte cell line. In this paper, both a shortened side-chain non-calcemic analog, (20S)-1alpha-hydroxy-2-methylene-19-nor-bishomopregnacalciferol (2MbisP), as well as a highly bone-selective compound, 2-methylene-19-nor-(20S)-1alpha-hydroxyvitamin D3 (2MD), are shown to completely prevent adipocyte differentiation in this cell line. 2MbisP is slightly less potent than 1,25(OH)2D3, whereas 2MD is approximately two orders of magnitude more potent that the parent hormone in preventing adipocyte differentiation.

Synthesis and preliminary chemotherapeutic evaluation of the fully C-linked glucuronide of N-(4-hydroxyphenyl)retinamide.

All-trans retinoic acid analogues such as N-(4-hydroxyphenyl)retinamide (4-HPR) are effective chemopreventive and chemotherapeutic agents but their utility has been hampered by dose-limiting side effects. The glucuronide derivatives of 4-HPR, the oxygen-linked 4-HPROG and the carbon-linked 4-HPRCG, have been found to be more effective agents. The synthetic route to the fully C-linked analogue of 4-HPROG (4-HBRCG), which employs Suzuki coupling and Umpolung chemistries as key methodologies, is shown.

All-trans retinoic acid-responsive genes identified in the human SH-SY5Y neuroblastoma cell line and their regulated expression in the nervous system of early embryos.

The vitamin A metabolite, all-trans retinoic acid (atRA), is required for embryonic development. atRA binds to the nuclear retinoic acid receptors and regulates the transcription of specific target genes. In order to identify atRA-induced genes that play a role in neural development, a subtractive library was created from SH-SY5Y neuroblastoma cells, a human cell line that exhibits changes in cell adhesion and neurite outgrowth after exposure to the vitamin A acid.