褪黑素调控动物繁殖功能的作用途径

褪黑素是由松果体分泌的一种多功能吲哚类激素,在动物繁殖过程中起了至关重要的作用.褪黑素可通过多条途径调控动物的繁殖功能,主要包括：G蛋白偶联受体途径;作为神经内分泌激素对动物繁殖进行调控;与其核受体结合在转录水平上调控动物繁殖;通过抗氧化作用调控卵泡发育.本文就褪黑素对动物繁殖功能的调控途径进行综述,旨在为褪黑素调控动物繁殖的相关研究提供帮助.     

Recent advances in reproductive neuroendocrinology: a role for RFamide peptides in seasonal reproduction?

Most temperate-zone species use photoperiod to coordinate breeding and ensure that offspring are born during favourable conditions. Although photoperiodic influences on the reproductive axis have been well characterized, the precise mechanisms by which photoperiodic information and other seasonal cues are integrated to regulate reproductive function remain less well specified. Two recently discovered neuropeptides, kisspeptin and gonadotropin-inhibitory hormone, have pronounced opposing influences on reproductive function. This paper will review recent evidence for a role of these peptides in seasonal reproduction and propose a theoretical framework by which these novel regulatory peptides may serve to regulate seasonal breeding. Understanding the mechanisms regulating appropriate changes in reproductive status will serve to advance a wide range of life science disciplines.     

Ligand binding to the human MT2 melatonin receptor: the role of residues in transmembrane domains 3, 6, and 7

To better understand the mechanism of interactions between G-protein-coupled melatonin receptors and their ligands, our previously reported homology model of human MT2 receptor with docked 2-iodomelatonin was further refined and used to select residues within TM3, TM6, and TM7 potentially important for receptor-ligand interactions. Selected residues were mutated and radioligand-binding assay was used to test the binding affinities of hMT2 receptors transiently expressed in HEK293 cells. Our data demonstrate that residues N268 and A275 in TM6 as well as residues V291 and L295 in TM7 are essential for 2-iodomelatonin binding to the hMT2 receptor, while TM3 residues M120, G121, V124, and I125 may participate in binding of other receptor agonists and/or antagonists. Presented data also hint at possible specific interaction between the side-chain of Y188 in second extracellular loop and N-acetyl group of 2-iodomelatonin.     

In vitro effects of strontium ranelate on the extracellular calcium-sensing receptor

The extracellular calcium-sensing receptor (CaSR) is activated by divalent cations and might mediate some of the effects of strontium ranelate, a new drug for the prevention and treatment of post-menopausal osteoporosis. Here, we showed that the maximal effect of Sr(2+) was comparable to that observed for Ca(2+) for both the cloned rat CaSR expressed in Chinese hamster ovary [CHO(CaSR)] cells and the mouse CaSR constitutively expressed in AtT-20 cells as measured by the accumulation of [(3)H]inositol phosphates (IP) resulting from CaSR activation. Strontium ranelate also displayed comparable agonist activity for the CaSR in both cell lines. Sodium ranelate did not stimulate the IP response in CHO(CaSR) cells. The IP response resulting from activation of other G-protein-coupled receptors was potentiated by Sr(2+), suggesting that entry of Sr(2+) into the cells might influence phospholipase C activity. Modulation of the CaSR activity in bone cells by strontium ranelate may contribute to its reported antiosteoporotic effects.     

基于LED作为照射光源的血疗法可行性研究

通过对LED在生物医学领域的应用分析发现,LED光存在与激光相类似的生物刺激效应。目前弱激光血疗已由血管内照射发展到体表照射、黏膜照射。这为LED光照射体表、黏膜实现血疗提供了良好的预期。为了证明LED光可以代替激光作为净血治疗仪的光源,本实验设计了激光与LED光对自由基损伤模型红细胞变形性作用的对比实验,结果表明,两种光照方法均对红细胞变形性有改善作用。LED相比激光安全性更好、成本更加低廉,特别适合往家用小型化方向发展。     

Efficient red-emitting cyclometalated iridium(III) complex and applications of organic light-emitting diode

Novel red phosphorescent emitter bis(2,3-diphenylquinolinato-N,C^2’) iridium(acetylacetonate) [(23dpq)₂Ir(acac)] has been synthesised and fully characterized. A highly efficient red organic light-emitting diode was fabricated by using (23dpq)₂Ir(acac) as an emitter, in which (23dpq)₂Ir(acac) was synthesised from a well-designed ligand-2,3-diphenylquinoline. Electroluminescent device with a configuration of ITO/2-TNATA/NPB/BAlq:(23dpq)₂Ir(acac)/AlQ₃/LiF/Al was fabricated. The device using (23dpq)₂Ir(acac) as a dopant showed pure-red emission with 1931 CIE (Commission International de L’Eclairage) chromaticity coordinates x = 0.66, y = 0.34.     

褪黑激素及其对动物生殖影响的研究进展

褪黑激素是由松果腺分泌的一种激素,在动物的生殖、生物钟、免疫、抗自由基等方面都有重要影响。简要综述了褪黑激素的主要理化性质及其生物学功能、褪黑激素受体,并总结了近年来褪黑激素对动物生殖影响的研究进展。     

IL-8 promotes cell proliferation and migration through metalloproteinase-cleavage proHB-EGF in human colon carcinoma cells

Interleukin-8 (IL-8) has been reported to promote tumor cell growth in colon cancer cells after binding to its receptors, which are members of the G-protein coupled receptor (GPCR) family. Recent studies demonstrated that stimulation of GPCR can induce shedding of epidermal growth factor (EGF) ligands via activation of a disintegrin and metalloprotease (ADAM), with subsequent transactivation of the EGF receptor (EGFR). In this study, we investigated mechanisms of cell proliferation and migration stimulated by IL-8 in a human colon carcinoma cell line (Caco2). IL-8 increased DNA synthesis of Caco2 in a dose dependent manner and this was inhibited by ADAM, EGFR kinase, and MEK inhibitors. IL-8 transiently induced EGFR tyrosine phosphorylation after 5-90 min and this was completely inhibited by ADAM inhibitor. Neutralizing antibody against HB-EGF as a key ligand for EGFR also blocked transactivation of EGFR and cell proliferation by IL-8. Since IL-8-induced cell migration was further suppressed by the ADAM inhibitor and the HB-EGF neutralizing antibody, our data indicate that IL-8 induces cell proliferation and migration by an ADAM-dependent pathway, and that HB-EGF plays an important role as the major ligand for this pathway.     

C-terminal splice variants of the mu-opioid receptor: existence, distribution and functional characteristics

The distribution of the mRNA of different C-terminal splice variants of the μ-opioid receptor in rat CNS was assessed by RT-PCR. The mRNA species for MOR1, MOR1A and MOR1B were readily detectable and distributed widely throughout the rat CNS, with levels of MOR1 and MOR1A mRNA being overall greater than for MOR1B. We did not find convincing evidence that significant levels of MOR1C, MOR1C1, MOR1C2 and MOR1D are present in rat CNS. To examine possible differences in the agonist-induced regulation of MOR1, MOR1A and MOR1B, we expressed these constructs in HEK293 cells along with G-protein-coupled inwardly rectifying K⁺ channel subunits and measured the rate and extent of desensitisation of ( d -Ala², N -Me-Phe⁴,glycinol⁵)-enkephalin (DAMGO)- and morphine-induced G-protein-coupled inwardly rectifying K⁺ currents. Morphine-induced desensitisation was rapid for all three splice variants ( t _½: 1.2–1.7 min) but DAMGO-induced desensitisation was significantly slower for MOR1B ( t _½ 4.2 min). Inhibition of endocytosis by expression of a dynamin-dominant negative mutant increased the rate of DAMGO-induced desensitisation of MOR1B. These data show that some splice variants of μ-opioid receptor are widely expressed in rat CNS but question the existence of others that have been reported in the literature. In addition, whereas the rate of desensitisation of MOR1 and MOR1A is agonist-independent, that for MOR1B is agonist-dependent.     

Regulation of the female rat estrous cycle by a neural cell-specific epidermal growth factor-like repeat domain containing protein,NELL2

NELL2, a protein containing epidermal growth factor-like repeat domains, is predominantly expressed in the nervous system. In the mammalian brain, NELL2 expression is mostly neuronal. Previously we found that NELL2 is involved in the onset of female puberty by regulating the release of gonadotropin-releasing hormone (GnRH), and in normal male sexual behavior by controlling the development of the sexually dimorphic nucleus of the preoptic area (POA). In this study we investigated the effect of NELL2 on the female rat estrous cycle. NELL2 expression in the POA was highest during the proestrous phase. NELL2 mRNA levels in the POA were increased by estrogen treatment in ovariectomized female rats. Blocking NELL2 synthesis in the female rat hypothalamus decreased the expression of kisspeptin 1, an important regulator of the GnRH neuronal apparatus, and resulted in disruption of the estrous cycle at the diestrous phase. These results indicate that NELL2 is involved in the maintenance of the normal female reproductive cycle in mammals.     

褪黑激素的研究进展

褪黑激素是一种在多个物种的多个组织中广泛存在并具有重要生理作用的激素。本文拟就褪黑激素在体内的分布,褪黑激素受体的分子结构、药理学特性、生物功能及调控模式作一简述。     

Latrophilin fragments behave as independent proteins that associate and signal on binding of LTX(N4C)

Heptahelical, or G-protein-coupled, receptors control many cellular functions and normally consist of one polypeptide chain. In contrast, heptahelical receptors that belong to the long N-terminus, group B (LNB) family are cleaved constitutively into two fragments. The N-terminal fragments (NTFs) resemble cell-adhesion proteins and the C-terminal fragments (CTFs) are typical G-protein-coupled receptors (GPCRs) with seven transmembrane regions. However, the functional roles of this cleavage and of any subsequent NTF-CTF interactions remain to be identified. Using latrophilin, a well-studied member of the LNB family, we now demonstrate that cleavage is critical for delivery of this receptor to the cell surface. On the plasma membrane, NTF and CTF behave as separate membrane proteins involved, respectively, in cell-surface reception and signalling. The two fragments can also internalise independently. However, separated NTF and CTF can re-associate on solubilisation. Agonist binding to NTF on the cell surface also induces re-association of fragments and provokes signal transduction via CTF. These findings define a novel principle of structural and functional organisation of the cleaved, two-subunit GPCRs.     

Molecular identification of nicotinic acid receptor

Nicotinic acid and its derivative, Acipimox, have been widely used in the treatment of hyperlipidemia. Pharmacological studies have demonstrated that they exert the beneficial effect through the activation of a Gi-protein-coupled receptor on adipocyte, which has remained elusive to date. Here we show that a novel GPCR, designated HM74b because of its high similarity to HM74, is a receptor for nicotinic acid. HM74b mRNA is found in human, murine, and rat adipose tissues. Nicotinic acid and Acipimox inhibit forskolin-stimulated intracellular cAMP accumulation in human HM74b-expressing cells and activate GTP gamma S binding in a dose-dependent manner. [3H]Nicotinic acid specifically binds to HM74b-expressing membrane and its binding is replaced by Acipimox. This finding will open a new phase of research on the physiological role of nicotinic acid and will be a clue to develop novel antihyperlipidemic drugs.