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．     

视黄类受体与视黄酸致畸作用关系

视黄酸（维甲酸）可引起包括人在内的多种动物胚胎畸形,其生物活性是由一系列视黄酸受体及其配体介导的。其中视黄类受体RAR起主要作用,RAR的配体为强致畸物,相对致畸活性由强至弱依次为配体α、配体β和配体γ。视黄酸受体RXR的配体无致畸活性,但是可加强RAR激动剂的某些致畸郊应。视黄酸受体还可通过其它基因的表达而影响胚胎发育。对视黄类受体基因突变和不同视黄类受体及其配体与致畸作用的关系,以及此类受体对其它基因表达的调节作简要综述。Abstract: Retinoic acid can induce teratogenesis of the fetus of many animals including human, and its biological activities are induced by a serious of different retinoic acid accepters and their ligands. The retinoic acid acceptor RAR plays key roles in the teratogenesis, and the legands of RAR are strong teratogens. The intensity sequence of the relative teratogenesis is ligandα、ligandβ and ligandγ. The ligands of the retinoic acid acceptor RXR cannot induce teratogenesis, but they can enhance the teratogenesis of the RAR stimulus. The retinoic acid acceptors can also affect the development of the fetus by adjusting the expression of the other genes. The relations between the gene mutation of the retinoic acid acceptor, various retinoic acid acceptors and their ligands and teratogenesis of retinoic acid are summarized in this article. In addition, the regulations of the retinoic acid acceptors to the other genes are also discussed.     

Regulation of Cardiac Energy Metabolism in Newborn

Energy in the form of ATP is supplied from the oxidation of fatty acids and glucose in the adult heart in most species. In the fetal heart, carbohydrates, primarily glucose and lactate, are the preferred sources for ATP production. As the newborn matures the contribution of fatty acid oxidation to overall energy production increases and becomes the dominant substrate for the adult heart. The mechanisms responsible for this switch in energy substrate preference in the heart are complicated to identify due to slight differences between species and differences in techniques that are utilized. Nevertheless, our current knowledge suggests that the switch in energy substrate preference occurs due to a combination of events. During pregnancy, the fetus receives a constant supply of nutrients that is rich carbohydrates and poor in fatty acids in many species. Immediately after birth, the newborn is fed with milk that is high in fat and low in carbohydrates. The hormonal environment is also different between the fetal and the newborn. Moreover, direct subcellular changes occur in the newborn period that play a major role in the adaptation of the newborn heart to extrauterin life. The newborn period is unique and provides a very useful model to examine not only the metabolic changes, but also the effects of hormonal changes on the heart. A better understanding of developmental physiology and metabolism is also very important to approach certain disorders in energy substrate metabolism.     

Increased p21 expression and complex formation with cyclin E/CDK2 in retinoid-induced pre-B lymphoma cell apoptosis

Cip/Kip family protein p21, a cyclin-dependent kinase (CDK) inhibitor, is directly transactivated by retinoic acid receptor alpha (RARalpha) upon retinoic acid (RA):RARalpha binding. Yet the role of p21 upregulation by RA in lymphoma cells remains unknown. Here, we show that, in human pre-B lymphoma Nalm6 cells, RA-induced proliferation inhibition results from massive cell death characterized by apoptosis. Upregulated p21 by RA accompanies caspase-3 activation and precedes the occurrence of apoptosis. p21 induction leads to increased p21 complex formation with cyclin E/CDK2, which occurs when cyclin E and CDK2 levels remain constant. CDK2 can alternatively promote apoptosis, but the mechanisms remain unknown. Data presented here suggest a novel RA-signaling, by which RA-induced p21 induction and complex formation with cyclin E/CDK2 diverts CDK2 function from normally driving proliferation to alternatively promoting apoptosis.     

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.     

Retinoic acid stimulates growth hormone synthesis in human somatotrophic adenoma cells: Characterization of its nuclear receptors

In order to gain a better understanding on the possible role of retinoic acid (RA) on human GH secretion, we have characterized the expression of its nuclear receptors in somatotropic adenoma cell extracts. By immunoblotting with rabbit polyclonal antibodies directed against RARα, β, and γ and RXRα and β, we could only detect the presence of RARα and RXRα proteins. The predominant expression of RXRα was confirmed at the mRNA level by Northern and slot-blot analysis. When then investigated the effect of RA on GH synthesis in cell culture of adenomatous somatotrophs. In cultured cells, RA (1 μM) stimulated GH secretion, increased intracellular GH content and GH mRNA levels within 72 h, suggesting a modulation of GH synthesis by RA. J. Cell. Biochem 65:25–31. © 1997 Wiley-Liss, Inc.     

Potential signal pathway of all-trans retinoic acid for MMP-2 and MMP-9 expression in injury podocyte induced by adriamycin

Abstract

All-trans-retinoic acid (ATRA) can regulate some specific genes expression in various tissue and cells via nuclear retinoic acid receptors (RARs), including three subtypes: retinoic acid receptor-alpha (RAR-α), retinoic acid receptor-beta (RAR-β) and retinoic acid receptor-gamma (RAR-γ). Podocyte injury plays a pivotal role in the progression of glomerulosclerosis (GS). This study was performed to study the potential signal pathway of ATRA in the expression of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9) in injury podocyte. Cells were divided into three groups: group of negative control (NC), group of injury podocyte induced by adriamycin (ADR) (AI) and group of ADR inducing podocyte injury model treated with ATRA (AA). The cells morphology changes were detected using microscope and scanning electron microscopy. MMP-2 and MMP-9 enzymic activity was detected using the gelatin zymography method. Protein and mRNA expressions of MMP-2, MMP-9, RAR-α, RAR-β and RAR-γ were measured by western-blot and real-time RT-PCR. Enzymatic activity of MMP-2 and MMP-9 in group AA was significantly enhanced compared to AI group after ATRA-treated 24?h (p?<?0.05). The protein and mRNA expressions of MMP-2/MMP-9 in group AA were significantly increased than those in group AI at both 12 and 24?h time points (p?<?0.05). Compared to group AI, RAR-α and RAR-γ protein/mRNA expressions of group AA were significantly increased at both 12 and 24?h time points (p?<?0.05). There was no difference for the expression of RAR-β between group AI and group AA (p?>?0.05). RAR-α protein level was positively correlated with MMP-2 or MMP-9 protein expression (p?<?0.05), and RAR-γ protein level was also positively correlated with MMP-2 or MMP-9 protein expression (p?<?0.05). In conclusion, ATRA may increase expression of MMP-2 and MMP-9 by the potential signal pathway of RAR-α and RAR-γ in injury podocyte induced by adriamycin, but not RAR-β.