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21.
Enteric nervous system (ENS) precursors undergo a complex process of cell migration, proliferation, and differentiation to form an integrated network of neurons and glia within the bowel wall. Although retinoids regulate ENS development, molecular and cellular mechanisms of retinoid effects on the ENS are not well understood. We hypothesized that retinoids might directly affect ENS precursor differentiation and proliferation, and tested that hypothesis using immunoselected fetal ENS precursors in primary culture. We now demonstrate that all retinoid receptors and many retinoid biosynthetic enzymes are present in the fetal bowel at about the time that migrating ENS precursors reach the distal bowel. We further demonstrate that retinoic acid (RA) enhances proliferation of subsets of ENS precursors in a time-dependent fashion and increases neuronal differentiation. Surprisingly, however, enteric neurons that develop in retinoid deficient media have dramatically longer neurites than those exposed to RA. This difference in neurite growth correlates with increased RhoA protein at the neurite tip, decreased Smurf1 (a protein that targets RhoA for degradation), and dramatically decreased Smurf1 mRNA in response to RA. Collectively these data demonstrate diverse effects of RA on ENS precursor development and suggest that altered fetal retinoid availability or metabolism could contribute to intestinal motility disorders. 相似文献
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B. Röll J. Schwemer 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1999,185(1):51-58
The ocular lenses of several genera of strictly diurnal dwarf geckos contain the monomeric ι-crystallin, which is closely
related to the cellular retinol-binding protein type I (CRBP I). The contents of ι-crystallin vary between 2 and 12% of the
total amount of crystallins depending on species. The endogenous ligand of ι-crystallin of all species investigated so far
turns out to be 3,4-didehydroretinol (vitamin A2). No other lenticular retinoids were detected. In lenses of Old World species (Lygodactylus, Pristurus, Quedenfeldtia), this ligand occurs exclusively in the all-trans form. In lenses of species of the neotropical genus Gonatodes, however, it occurs in two isomeric forms: all-trans and 11-cis. ι-Crystallin of Gonatodes is the first CRBP-like protein which naturally binds an 11-cis isomer of vitamin A. All-trans 3,4-didehydroretinol and its ester are present in eye cups of Lygodactylus. In contrast, eye cups of nocturnal geckos without ι-crystallin lack these retinoids. The retinal pigment epithelium is suggested
to be the site of conversion of retinol to 3,4-didehydroretinol, which finally serves as ligand of ι-crystallin.
Accepted: 13 March 1999 相似文献
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I. A. Niaze 《Journal of biosciences》1996,21(3):273-297
Studies on the effects of exogenous vitamin A palminate on limb development and regeneration in anuran tadpoles carried out
since late 1960s at the author’s laboratory are reviewed and discussed. Most significant was the initial discovery that vitamin
A causes regeneration of complete or nearly complete limbs instead of only the missing distal part, thus altering the P-D
pattern of regeneration—a phenomenon now called proximalization. Often more than one such regenerates develop per stump. Vitamin
A produces proximalizing effect on regeneration cells during their dedifferentiation and blastema formation but inhibits regeneration
if given once redifferentiation begins. Shank-level blastemas from treated tadpoles grafted into orbits of previously treated/untreated
host tadpoles formed complete limbs. Proximalizing effect is proportionate to vitamin A concentration, duration of treatment,
amputational level and stage of tadpoles. Vitamin A produces this effect also if given only prior to amputation. Its influence
persists after cessation of treatment, declining with time. Proximalizing effect is correlated with natural ability in limbs
to regenerate. Vitamin A improves regenerative ability and can induce it to some extent in non-regenerating limbs. Vitamin
A excess retards limb development and produces stage dependent teratogenic defects. Further development of only that limb
region is prevented in which differentiation is beginning when vitamin A is given. Short treatment of tadpoles beginning with
limbs at spatula/paddle stage inhibited foot development in the unoperated limbs hut promoted regeneration of complete limbs
from the contra-lateral amputated limbs. These dual effects were due to cells of the former differentiating and of the latter
dedifferentiating when exposed to vitamin A palmitate. 相似文献
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Preejith P. Vachali Brian M. Besch Federico Gonzalez-Fernandez Paul S. Bernstein 《Archives of biochemistry and biophysics》2013
Uptake, transport and stabilization of xanthophylls in the human retina are important components of a complex multistep process that culminates in a non-uniform distribution of these important nutrients in the retina. The process is far from understood; here, we consider the potential role of interphotoreceptor retinoid-binding protein (IRBP) in this process. IRBP is thought to facilitate the exchange of 11-cis-retinal, 11-cis-retinol and all-trans-retinol between the retinal pigment epithelium (RPE), photoreceptors and Müller cells in the visual cycle. Structural and biochemical studies suggest that IRBP has a variety of nonequivalent ligand binding sites that function in this process. IRBP is multifunctional, being able to bind a variety of physiologically significant molecules including fatty acids in the subretinal space. This wide range of binding activities is of particular interest because it is unknown whether the lutein and zeaxanthin found in the macula originate from the choroidal or retinal circulations. If from the choroidal circulation, then IRBP is a likely mediator for their transport across the interphotoreceptor matrix. In this report, we explore the binding interactions of retinoids, fatty acids, and carotenoids with IRBP using surface plasmon resonance (SPR)-based biosensors. IRBP showed similar affinity toward retinoids and carotenoids (1–2 μM), while fatty acids had approximately 10 times less affinity. These results suggest that further studies should be carried out to evaluate whether IRBP has a physiologically relevant role in binding lutein and zeaxanthin in the interphotoreceptor matrix. 相似文献
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Yuta Takamura Osamu Shibahara Masaki Watanabe Michiko Fujihara Shoya Yamada Masaru Akehi Takanori Sasaki Hiroyuki Hirano Hiroki Kakuta 《Bioorganic & medicinal chemistry》2019,27(14):3128-3134
Bexarotene (1), a retinoid X receptor (RXR) agonist approved for the treatment of cutaneous T cell lymphoma (CTCL), was reported to migrate into baboon brain based on findings obtained by positron emission tomography (PET) with a 11C-labeled tracer. However, co-administration of non-radioactive 1 had no effect on the distribution of [11C]1, probably due to non-specific binding of 1 as a result of its high lipophilicity. Here, we report a fluorine-18 (18F)-labeled PET tracer [18F]6 derived from RXR partial agonist CBt-PMN (2), which has lower lipophilicity and weaker RXR-binding ability than [11C]1. The concomitant administration of 1 or 2 with [18F]6 with resulted in decreased accumulation of [18F]6 in liver, together with increased brain uptake and increased accumulation in kidney and muscle, as visualized by PET. A plausible explanation of these findings is the inhibition of [18F]6 uptake into the liver by concomitantly administered 1 or 2, leading to an increase in blood concentration of [18F]6 followed by increased accumulation in other tissues. 相似文献
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Uptake of dietary retinoids at the maternal-fetal barrier: in vivo evidence for the role of lipoprotein lipase and alternative pathways 总被引:1,自引:0,他引:1
Dietary retinoids (vitamin A and its derivatives) contribute to normal embryonic development. However, the mechanism(s) involved in the transfer of recently ingested vitamin A from mother to embryo is not fully understood. We investigated in vivo whether lipoprotein lipase (LPL) facilitates the placental uptake of dietary retinyl ester incorporated in chylomicrons and their remnants and its transfer to the embryo. We examined the effects of both genetic ablation (MCK-L0 mice) and pharmacological inhibition (P-407) of LPL by maintaining wild type and MCK-L0 mice on diets with different vitamin A content or administering them an oral gavage dose of [(3)H]retinol with or without P-407 treatment. We showed that LPL expressed in placenta facilitates uptake of retinoids by this organ and their transfer to the embryo, mainly through its catalytic activity. In addition, through its "bridging function," LPL can mediate the acquisition of nascent chylomicrons by the placenta, although less efficiently. Quantitative real-time PCR and Western blot analysis showed that placental LPL acts in concert with LDL receptor and LRP1. Finally, by knocking out the retinol-binding protein (RBP) gene in the MCK-L0 background (MCK-L0-RBP(-/-) mice) we demonstrated that the placenta acquires dietary retinoids also via the maternal circulating RBP-retinol complex. RBP expressed in the placenta facilitate the transfer of postprandial retinoids across the placental layers toward the embryo. 相似文献
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