The effect of vitamin A (retinoids) on pattern formation implies a uniformity of developmental mechanisms throughout the animal kingdom

Retinoids are low molecular weight, lipophilic derivatives of vitamin A which have a profound effect upon the development of a diverse array of animals. Here, I review these effects on Invertebrates: a colonial hydroid, a colonial ascidian, and Vertebrates: the regenerating amphibian limb, the developing chick limb bud, the regenerating amphibian tail, the anteroposterior axis of the early embryo, the developing chick embryo skin. There is a striking uniformity of effect of retinoids on pattern formation when applied to these diverse organisms. The majority react by being posteriorized in their development, although additional effects can also be seen. Several hypotheses which can explain these results are discussed along with the deduction that they lead to: retinoids may be components of a universal developmental mechanism or they may simply act in a similar way to alter a universal developmental mechanism. In either case the experimental analysis of retinoid effects on development has important implications for the evolution of developmental mechanisms.     

细胞内视黄酸信号传递系统

视黄酸对基因表达的调控与肿瘤细胞的分化、胚胎的发育以及疾病的发生关系密切．视黄酸的基因调控作用是通过视黄酸信号传递系统实现的．视黄酸信号传递系统包括视黄酸、细胞液视黄醇（酸）结合蛋白、视黄酸细胞核受体及视黄酸反应元件等．视黄酸信号传递系统自成一体系,在这一系列调控的级联反应中存在着多级反馈调控环节,而且该系统还与视黄酸配体以外的信号系统相联系．     

Endogenous retinoids in the hair follicle and sebaceous gland

Vitamin A and its derivatives (retinoids) are critically important in the development and maintenance of multiple epithelial tissues, including skin, hair, and sebaceous glands, as shown by the detrimental effects of either vitamin A deficiency or toxicity. Thus, precise levels of retinoic acid (RA, active metabolite) are needed. These precise levels of RA are achieved by regulating several steps in the conversion of dietary vitamin A (retinol) to RA and RA catabolism. This review discusses the localization of RA synthesis to specific sites within the hair follicle and sebaceous gland, including their stem cells, during both homeostasis and disease states. It also discusses what is known about the specific roles of RA within the hair follicle and sebaceous gland. This article is part of a Special Issue entitled: Retinoid and Lipid Metabolism.     

Properties of retinoids

Retinoids are unstable compounds being readily oxidized and/or isomerized to altered compounds, especially in the presence of oxidants including air, light, and excessive heat. They are labile toward strong acids and solvents that have dissolved oxygen or peroxides. In this review, procedures for handling and storage of retinoids and biological samples containing them have been described. The physical and chemical properties of retinoids have been reported. Simplified procedures for derivatizations and purification, and methods for quantitation of retinoids have been presented.     

Rapid reset of the corticosterone rhythm by food presentation in rats under acircadian restricted feeding schedule

Corticosterone levels were determined in the 7-week-old male rat maintained under different feeding and lighting schedules. At 4 weeks of age, the animals were kept either under a natural photoperiod (LD) or were subjected to continuous illumination (LL). Access to food was either ad libitum or restricted to an 8 hr span per 24 hr (circadian) or 32 hr (acircadian).

The food signal seemed able to synchronize the corticosterone rhythm to its own circadian periodicity, irrespective of the lighting regimen. No synchronization was observed in serially sampled LL or LD rats under an acircadian feeding schedule. Instead, the group acrophase appeared 24 hr subsequent to food presentation. Regarding individual patterns, many rats showed an acrophase or a peak also at that time. We speculate that an endogenous circadian mechanism was reset by the food signal, whenever it appeared.     

Expression of cellular retinoc acid-binding protein I is specific to neurons in adult transgenic mouse brain

Cellular retinoic acid binding protein I (CRABP-I) plays a role in retinoic acid (RA) metabolism or transport. This report shows specific neuronal expression of CRABP-I in adult transgenic mouse brain using CRABP-I promotor-driven lac-Z and neuron- and astrocyte-markers. Double staining indicates that CRABP-I is expressed in neurons and large cells (>12 μm) but to much lesser degree the astrocytes. CRABP-I-lac-Z⁺ neurons were distributed throughout the brain, but in a very discreet pattern in each brain region. CRABP-I expression in specific populations of brain neurons suggests that RA is extensively metabolized in mature brains, mostly in neurons. Additionally, the genetic basis of its specific expression in these brain areas is located in the 5′ regulatory region of this gene.     

Retinoic Acid Improves a Hybridoma Culture in a Fructose-Based Medium by Up-Regulation of Fructose Incorporation via Retinoid Nuclear Receptors

Fructose was focused on as an alternative sugar source to glucose in a hybridoma culture medium because it decreases lactate production during cultivation, leading to cell and product stability. But, not all human hybridoma cell lines grew well in a fructose-based serum-free medium. We found that the addition of all-trans-retinoic acid to the fructose-based medium improved the growth and monoclonal antibody production of hybridoma cell lines by up-regulation of fructose incorporation that represented increased expression of the fructose transporter, GLUT5. Selective activation of retinoid nuclear receptor by synthetic ligands showed that both retinoic acid receptors and retinoid X receptors might be related to the improvement of the fructose-based hybridoma culture. This study might be applicable to cell cultures susceptible to lactate and pH changes as well as hybridoma cultures.     

Retinoid teratogenicity in the macaque: verification of dosing regimen

To further define teratogenicity associated with 13-cis-retinoic acid (13-cis-RA) in the cynomolgus monkey, the drug was orally administered on three different treatment regimens. Experiment (Exp.) 1 (2.5 mg/kg/day, gestational day [GD] 12-27, n = 11) investigated the teratogenicity of a single daily dose of 13-cis-RA administered shortly after embryo implantation. Pharmacokinetic sampling was done to determine retinoid profiles on the first (GD12) and last (GD27) days of treatment. Exposure to 13-cis-RA during early organogenesis in Exp. 2 (2.5 mg/kg/day, GD20-27, and 2 x 2.5 mg/kg/day, GD28-30, n = 5) investigated the potential adverse effects of 13-cis-RA on the developing limb. The use of multiple doses of 13-cis-RA in Exp. 3 (2 x 2.5 mg/kg/day, GD26-27, n = 5) investigated the necessity of double dosing on the induction of retinoid embryopathy in the macaque. Malformations of retinoid target organs as well as embryolethality were most prevalent when single daily doses of 13-cis-RA were administered during pre- and early organogenesis in Exp. 1. Moreover, multiple doses on GD26-27 failed to induce any manifestation of abnormal development in Exp. 3. These results confirm that the lowest observed adverse effect level (LOAEL) in macaques is 2.5 rather than 5.0 times greater than that observed in human pregnancies. Exposure during forelimb development (GD20-30) in Exp. 2 was unsuccessful in inducing defects of this skeletal region, although defects in several retinoid target organs (i.e., cerebellum and internal ear) were present, indicating that a teratogenic threshold was achieved. Pharmacokinetic analysis of 13-cis-RA and its metabolites on GD12 and 27 in Exp. 1 showed considerable exposure to the administered drug and its 4-oxo-metabolite. In contrast, the exposure to all-trans-RA was negligible. The results support the use of a specific treatment schedule in early gestation in the macaque as the most appropriate model for characterizing the teratogenic potential of retinoids in humans.     

肿瘤鞘脂代谢异常与肿瘤细胞对维甲酸类药物耐药性

维甲酸类药物对多种癌症有效,其作用包括诱导凋亡、抑制生长、促进分化等,这主要通过调节维甲酸受体包括维甲酸受体(retinoic acid receptor,RAR)和维甲酸X受体(rexinoid X receptor,RXR)的表达实现。目前发现,一些患者癌细胞的RAR、RXR或RAR/RXR表达缺乏,可能导致癌细胞对维甲酸产生耐药性。鞘脂代谢异常和维甲酸类受体表达缺失密切相关,在癌细胞对维甲酸产生耐药性中发挥着重要作用。本文就鞘脂代谢异常与维甲酸受体表达异常及维甲酸类药物耐药的相关性做一简要综述。     

The adult eclosion rhythm in Hyphantria cunea (Lepidoptera: Arctiidae): Endogenous and exogenous light effects

Abstract

Endogenous and exogenous effects of light on adult eclosion in Hyphantria cunea were tested by exposure to various light regimes. Regression analysis showed that the position of the eclosion peak after lights on was proportional to the length of the photophase, and that the peak was influenced by the timing of both lights‐on and lights‐off. Under photoperiods of 2–12 hours LD cycle, the eclosion peak was situated after lights‐off, but moved into the light phase as the photophase increased to 22 hours. Pupae were exposed to 3 “skeleton”; photoperiods of LDLD2:2:6:14, 4:2:4:14 and 6:2:2:14. Under the first of these, most adults emerged at the start or just before the longest dark period. Under the second and third skeleton regimes, 20% and 70% respectively of pupae emerged during the shorter dark period. When the compound eyes of the pharate adults were covered, adults smerged 1–4 hours before lights‐off under LD10:14, compared to a control group which emerged just after lights‐off. When pupae were transferred from LD to LL or DD conditions, the eclosion peak occurred approximately every 24 hours after the last LD peak. Results suggest that light received by the compound eyes influences the eclosion rhythm, either through an exogenous masking effect, or by altering the phase of the pacemaker controlling eclosion.     

Circadian locomotory rhythm and the influence of moulting in Australian field cricket nymphs

ABSTRACT. Evidence is presented for a circadian control of locomotory activity in the larval stadia of the cricket, Teleogryllus commodus Walker. Under light—dark cycles (LD), maximal activity occurs around the L/D transition and/or in the hours preceding it. Free-running rhythm patterns longer than 24 h are observed in constant light. Re-entrainment to phase advances in the LD cycle is also accompanied by several transient cycles. However, free-running rhythms under constant darkness or transients when exposed to LD cycle delays were not found. LD cycles during the eighth stadium set the phase of a free-running rhythm in the adult, even if the nymph does not show a rhythm. Nymphal activity is often erratic and is disrupted periodically by the moulting cycle, but moulting does not interrupt the operation of the circadian system. The daily timing of the moult itself is not under circadian control.