Identification of a second human retinoic acid receptor

We have previously described a human complementary DNA that encodes a novel protein which is homologous to members of the steroid/thyroid nuclear receptor multigene family. This novel protein (hap for hepatoma) exhibits strong homology with the human retinoic acid receptor (RAR) which has been recently characterized. To test the possibility that the hap protein might also be a retinoid receptor, a chimaeric receptor was created by replacing the putative DNA binding domain of hap with that of the human oestrogen receptor (ER). The resulting hap-ER chimaera was then tested for its ability to trans-activate an oestrogen-responsive reporter gene (vit-tk-CAT) in the presence of possible receptor ligands. Here we show that retinoic acid (RA) at physiological concentrations is effective in inducing the expression of this reporter gene by the hap-ER chimaeric receptor. This demonstrates the existence of two human retinoic acid receptors designated RAR-alpha and RAR-beta.     

超氧化物歧化酶在斑马鱼早期胚胎中的表达特点

以斑马鱼早期胚胎为研究对象，通过免疫组织化学的方法研究了超氧化物歧化酶（SOD）在斑马鱼体节分化时期的表达特点。结果发现：在体节分化的不同时期，SOD在脊索细胞的胞质部位有不同强度的表达；SOD在脑组织中表达较强，到孵化期，在大脑区域的表达略强于间脑区域。提示SOD不仅存在于成体的抗氧化防线中，在胚胎早期发育过程中以SOD为代表的酶性抗氧化系统就开始逐步建立，维持胚胎组织器官细胞中的正常活性氧浓度，确保胚胎的正常发育。     

Identification of a novel retinoic acid receptor in regenerative tissues of the newt

In urodele amphibians, the progenitor cells that regenerate amputated limbs (known as the blastema) normally replace only the missing structures. After systemic delivery of retinoic acid (RA), more proximal structures are also formed, indicating that RA can control position specification in the proximal-distal axis of the regenerating limb. According to dose and experimental context, retinoids can also re-specify the anteroposterior axis of the limb, induce deletions of skeletal elements, or block re-growth completely. To study the molecular basis of these morphogenetic effects, we screened complementary DNA libraries of newt regenerative tissues (limbs and tails) for hormone nuclear receptors activated by RA. Two functional retinoic acid receptors (RARs) were identified, one of which is the newt homologue of the human alpha-receptor (RAR alpha). The second receptor, called RAR delta, is novel. Sequence analysis suggests that the composite newt RAR previously reported is chimaeric, consisting of 5'RAR-beta-like and 3' RAR delta clones. We conclude that multiple RARs are expressed during limb regeneration in amphibians and suggest that receptor heterogeneity may underlie the different effects of retinoids on limb morphogenesis.     

A new retinoic acid receptor identified from a hepatocellular carcinoma

Processes as diverse as growth, vision and reproduction depend on the presence of vitamin A and its metabolites (retinoids), but the molecular mechanisms which govern these diverse actions remain unclear (for reviews see refs 1,2). A crucial advance recently was the isolation of a specific nuclear receptor for retinoic acid, one of the physiologically active vitamin A derivatives. This nuclear receptor is a member of the steroid/thyroid hormone receptor family. Our analysis of an uncharacterized member of this class of intracellular receptors, encoded by a complementary DNA clone from a human placental library, has led us to discover a second retinoic acid receptor. This new receptor is expressed at high levels in a number of epithelial-type tissues. The gene for the receptor was first identified in a hepatocellular carcinoma where it surrounds a site of integration of hepatitis B virus. Activation by this virus may play a role in tumour development in liver cells, where it is normally not expressed.     

A human retinoic acid receptor which belongs to the family of nuclear receptors

A cDNA encoding a protein that binds retinoic acid with high affinity has been cloned. The protein is homologous to the receptors for steroid hormones, thyroid hormones and vitamin D3, and appears to be a retinoic acid-inducible trans-acting enhancer factor, suggesting that the molecular mechanisms of the effect of retinoids (vitamin A) on embryonic development, differentiation and tumour cell growth are similar to those described for other members of this nuclear receptor family.     

9-cis retinoic acid stereoisomer binds and activates the nuclear receptor RXR alpha.

Vitamin A (retinol) and its natural derivatives are required for many physiological processes. The activity of retinoids is thought to be mediated by interactions with two subfamilies of nuclear retinoic acid receptors, RAR and RXR. The RARs bind all-trans retinoic acid (t-RA) with high affinity and alter gene expression as a consequence of this direct ligand interaction. RXR alpha is activated by t-RA, yet has little binding affinity for this ligand. t-RA may be converted to a more proximate ligand that directly binds and activates RXR alpha, and we have developed a method of nuclear receptor-dependent ligand trapping to test this hypothesis. Here we report the identification of a stereoisomer of retinoic acid, 9-cis retinoic acid, which directly binds and activates RXR alpha. These results suggest a new role for isomerization in the physiology of natural retinoids.     

铜陵市酸雨时空分布特征及其成因分析

文章利用铜陵市2006-2010年的酸雨观测数据、降水化学分析资料和常规空气质量及气象资料,结合多种统计分析方法,系统地研究了铜陵市酸雨的分布特征、化学组成特征,并对其成因进行了初步探讨。结果表明:铜陵市的酸雨污染日趋严重,降水酸度在秋、冬季略高,郊区酸雨较城区严重;铜陵市的酸雨污染属于硫酸型,SO42-和NO3-是主要的阴离子,Ca2+和NH4+是主要的阳离子,各种离子浓度具有明显的局地差异,郊区低于城区,Ca2+和NH4+对降水酸度影响较为显著;铜陵市酸雨污染受区域性酸雨污染和本地污染源共同影响。     

Spatial and temporal patterns of Krüppel gene expression in early Drosophila embryos

The Krüppel (Kr) locus is a member of the 'gap' class of segmentation genes of Drosophila melanogaster. Mutations at the Kr locus cause the deletion of contiguous segments from the embryonic body pattern. We have elucidated the spatial and temporal characteristics of Kr gene expression during early embryo development, the localization of cytoplasmic Kr+ activity and its spatial requirement for normal segmentation.     

Homodimer formation of retinoid X receptor induced by 9-cis retinoic acid.

Retinoid response pathways are mediated by two classes of receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). A central question is whether distinct response pathways are regulated by these two classes of receptors. The observation that the stereoisomer 9-cis-retinoic acid binds with high affinity to RXRs suggested that this retinoid has a distinct role in controlling RXR activity, but it was almost simultaneously discovered that RXRs function as auxiliary receptors for RARs and related receptors, and are essential for DNA binding and function of those receptors. Hence, although RARs seem to operate effectively only as heterodimeric RAR/RXR complexes, RXRs themselves apparently function predominantly, if not exclusively, as auxiliary receptors. Here we report that 9-cis-retinoic acid induces RXR homodimer formation. Our results demonstrate a new mechanism for retinoid action by which a ligand-induced homodimer mediates a distinct retinoid response pathway.     

全反式维甲酸对HL—60细胞hTERT基因表达和端粒酶活性的影响

目的：探讨全反式维甲酸（ATRA）诱导HL－60细胞分化过程中人类端粒酶逆转录酶（hTERT)蛋白表达和端粒酶活性的改变,方法：应用间接免疫荧光标记法通过流式细胞仪检测hTERT蛋白含量的变化;采用多聚酶链反应－酶联免疫反应（PCR－ELISA）方法检测ATRA处理HL－60细胞前后端粒酶活性的改变,用碘化丙锭染色经流式细胞仪检测细胞周期的变化,结果：ATRA作用于HL－60细胞后,细胞内hTERT蛋白含量逐渐降低,细胞的端粒酶活性相应受到抑制。结论：在IL－60细胞分化过程中,可以通过hTERT基因的表达下调而抑制端粒酶的活性。