Pituitary adenylate cyclase-activating polypeptide

Pituitary adenylate cyclase-activating polypeptide (PACAP) which belongs to the secretin/glucagon/ VIP family has been originally isolated from the sheep hypothalamus on the basis of its ability to stimulate cAMP formation in culture rat anterior pituitary cells. Post-translational processing of the PACAP precursor generates two biologically active molecular forms, PACAP-38 and PACAP-27. The primary structure of PACAP has been remarkably conserved during evolution. The sequence of PACAP-27 exhibits substantial similarities with those of vasoactive intestinal polypeptide (VIP), glucagon and secretin. The gene encoding the PACAP precursor is widely expressed in brain and various peripheral organs, notably in endocrine glands, gastro-intestinal, urogenital tracts and respiratory system. In vivo, and in vitro studies have shown that PACAP exhibits multiple activities especially a trophic activity during ontogenesis, notably in the adrenal medulla and the central nervous system. The biological effects of PACAP are mediated through three distinct receptor subtypes which exhibit differential affinities for PACAP and VIP. The PAC1 receptor, which shows high selectivity for PACAP, is coupled to several transduction systems. In contrast, VPAC1 and VPAC2, which bind with the same affinity for PACAP and VIP, are mainly coupled to the adenylyl cyclase pathway. In conclusion, PACAP is neuropeptide, and it functions as a hypothalamic hormone, neurohormone, neuromodulator, vasodilator, neurotransmitter or trophic factor in the brain and the various organs.

A novel antimicrobial peptide from salivary glands of the hard tick, Ixodes sinensis

A novel antimicrobial peptide named as ixosin was isolated from the salivary glands of the hard tick, Ixodes sinensis, by gel filtration, ion exchange chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC). Its amino acid sequen

An immunoregulatory peptide from salivary glands of the horsefly, Hybomitra atriperoides

Horseflies are economically important blood-feeding arthropods and also a nuisance for humans, and vectors for filariasis. They rely heavily on the pharmacological propriety of their saliva to get blood meat and suppress immune reactions of hosts. Little information is available on horsefly immune suppressants. By high-performance liquid chromatography (HPLC) purification coupling with pharmacological testing, an immunoregulatory peptide named immunoregulin HA has been identified and characterized from salivary glands of the horsefly of Hybomitra atriperoides (Diptera, Tabanidae). Immunoregulin HA could inhibit the secretion of interferon-gamma (IFN-gamma) and monocyte chemoattractant protein (MCP-1) and increase the secretion of interteukin-10 (IL-10) induced by lipopolysaccharide (LIPS) in rat splenocytes. IL-10 is a suppressor cytokine of T-cell proliferative and cytokine responses. IL-10 can inhibit the elaboration of pro-inflammatory cytokines. Immunoregulin HA possibly unregulated the IL-10 production to inhibit IFN-gamma and MCP-1 secretion in the current experiments. This immunosuppression may facilitate the blood feeding of this horsefly. The current works will facilitate to understand the molecular mechanisms of the ectoparasite-host relationship. 2008 Elsevier Ltd. All rights reserved.

Toward an understanding of the molecular mechanism for successful blood feeding by coupling proteomics analysis with pharmacological testing of horsefly salivary glands

Horseflies are economically important blood-feeding arthropods and also a nuisance for humans and vectors for filariasis. They rely heavily on the pharmacological properties of their saliva to get a blood meal and suppress immune reactions of hosts. Little information is available on antihemostatic substances in horsefly salivary glands; especially no horsefly immune suppressants have been reported. By proteomics or peptidomics and coupling transcriptome analysis with pharmacological testing, several families of proteins or peptides, which act mainly on the hemostatic system or immune system of the host, were identified and characterized from 30,000 pairs salivary glands of the horsefly Tabanus yao (Diptera, Tabanidae). They are: (i) a novel family of inhibitors of platelet aggregation including two members, which possibly inhibit platelet aggregation by a novel mechanism and act on platelet membrane, (ii) a novel family of immunosuppressant peptides including 12 members, which can inhibit interferon-gamma production and increase interleukin-10 secretion, (iii) a serine protease inhibitor with 56 amino acid residues containing anticoagulant activity, (iv) a serine protease with anticoagulant activity, (v) a protease with fibrinogenolytic activity, (vi) three families of antimicrobial peptides including six members, (vii) a hyaluronidase, (viii) a vasodilator peptide, which is an isoform of vasotab identified from Hybomitra bimaculata, and interestingly (ix) two metallothioneins, which are the first metallothioneins reported from invertebrate salivary glands. The current work will facilitate the understanding of the molecular mechanisms of the ectoparasite-host relationship and help in identifying novel vaccine targets and novel leading pharmacological compounds.

Anti-thrombosis Repertoire of Blood-feeding Horsefly Salivary Glands

Blood-feeding arthropods rely heavily on the pharmacological properties of their saliva to get a blood meal and suppress immune reactions of hosts. Little information is available on antihemostatic substances in horsefly salivary glands although their sal

Two Immunoregulatory Peptides with Antioxidant Activity from Tick Salivary Glands

Ticks are blood-feeding arthropods that may secrete immunosuppressant molecules, which inhibit host inflammatory and immune responses and provide survival advantages to pathogens at tick bleeding sites in hosts. In the current work, two families of immunoregulatory peptides, hyalomin-A and -B, were first identified from salivary glands of hard tick Hyalomma asiaticum asiaticum. Three copies of hyalomin-A are encoded by an identical gene and released from the same protein precursor. Both hyalomin-A and -B can exert significant anti-inflammatory functions, either by directly inhibiting host secretion of inflammatory factors such as tumor necrosis factor-alpha, monocyte chemotectic protein-1, and interferon-gamma or by indirectly increasing the secretion of immunosuppressant cytokine of interleukin-10. Hyalomin-A and -B were both found to potently scavenge free radical in vitro in a rapid manner and inhibited adjuvant-induced inflammation in mouse models in vivo. The JNK/SAPK subgroup of the MAPK signaling pathway was involved in such immunoregulatory functions of hyalomin-A and -B. These results showed that immunoregulatory peptides of tick salivary glands suppress host inflammatory response by modulating cytokine secretion and detoxifying reactive oxygen species.

Toxicological Research on Environmental Endocrine Disruptors

Most evidence in terms of endocrine dsiruptors (EDs) mainly originates from studies on reproductive organs. However, in veterbrates, the ability to attain reproductive and development success relays on the intact organization of a complex endocrine system. Disturbances in the regulation of the key hormones and receptors functioning along this system may cause detrimental effects on reproduction and development. Here we reviewed recent studies of EDs on endocrine system. EDs may act on key hormones and receptors along with the hypothalarnic-pituitary-gonald (HPG) axis and lead to reproductive failure. Thyroid disruption may be caused at different levels, for example, the synthesis, transport, binding and cellular uptake along with the hypothalamic-pituitary-thyroid (HPT) axis. Knowledge of model of action EDs is largely via receptors-mediated pathway and alternatively may affect on steroid hormone synthesis. Aquatic hypoxia can influence fish reproduction and thus it is also an endocrine disruptor. Molecular techniques, such as toxicomics, transgenic fish will be employed as powerful tools for environmental EDs risk assessment, as well as in elucidating mechanisms of model action.

Hydroxylated metabolites of polychlorinated biphenyls and their endocrine disrupting mechanism

Hydroxylated polychlorinated biphenyls (OH-PCBs a group of main active metabolites of polychlorinated biphenyl (PCBs) which are typical persistent organic pollutants (Pops) I have been identified in wild animals and human. The endocrine disruption of OH-PCBs has been drawn great attention due to the similarity of their chemical structures to the natural estrogens and thyroid hormones. The metabolic pathways of PCBs, the levels of OHPCBs in organism, the endocrine disruption and other adverse effects of OH-PCBs are reviewed. The further investigation of OH-PCBs will not only reveal the toxicological mechanism of PCBs, but also can lay scientific basis for setting up the risk assessment of POPs contamination and early-warning system in China.

Evaluation of soot particles of biomass fuels with endocrine-modulating activity in yeast-based bioassay

Exposure to indoor air pollution (IAP) from the combustion of biomass fuels is an important cause of morbidity and mortality in developing countries. In the work discussed in this paper we evaluated the endocrine activity of soot particles from biomass fuels by using yeast bioassay. These pollutants could have beta-galactosidase activity with a relative potency (RP) about 10(-7)-10(-9) that of estradiol. Soot particles from wood and straw combustion only partially induced beta-galactosidase activity whereas others produced fully inductive activity in the yeast assay system. These pollutants did not have estrogen antagonist and progesterone agonist activity within the defined concentration range. However, these pollutants require 2-4 orders of magnitude higher IC50 to inhibit the activity of progesterone in a similar dose-response manner to mifepristone. We therefore propose that the endocrine activity of some environmental pollutants may be because of inhibition of the progesterone receptor (hPR). GC-MS results showed that substituted polycyclic aromatic hydrocarbon (PAH) compounds, substituted phenolic compounds and derivatives, aromatic carbonyl compounds, and phytosteroids in these soot particles may be mimicking endogenous hormones.

The Chinese rare minnow (Gobiocypris rarus) as an in vivo model for endocrine disruption in freshwater teleosts: a full life-cycle test with diethylstilbestrol

Chinese rare minnow (Gobiocypris rarus), a freshwater teleost,. was exposed to diethylstilbestrol (DES) at 0.05, 0.5, 1 and 5 mug/L from fertilized eggs for up to mature period under flow-through condition. Several endpoints that related to development, reproductive fitness and transgenerational effects were evaluated. It was found that body length and body weight were significantly reduced and vitellogenin (Via) levels were significantly increased for fish exposed to DES. Histological examination showed that the sex ratios of F-0 fish skewed to female and about 2% of the fish exposed to 0.05 mug/L DES developed testes-ova. The reproductive success, as determined from data on egg production, was reduced in female fish exposed to 0.05, 0.5, 1 and 5 mug/L DES. The lowest-observed-effect concentrations (LOEC) for chances of sex ratios, reproductive success and histology alteration of F-0 are 0.05 mug/L. In the offspring, transgenerational effects on egg hatching rate. egg fertilization and Vtg levels of juvenile individuals were not observed. However. survival of F, generation fry significantly declined. The analysis of sex steroid levels revealed a significant decrease of testosterone (T) in the whole body homogenates (WBH) of male progeny and somewhat elevation of estradiol (E-T) in the WBH of female offspring. These findings indicate that exposure to DES causes a variety of developmental, reproductive and transgenerational effects. (C) 2004 Elsevier B.V. All rights reserved.

Endocrine disrupting effects on Chinese rare minnow (Gobiocypris rarus) fed with field collected Limnodrilus sp.

The potential endocrine disrupting effects and other toxicity effects on aquatic biota resulted from food uptake was simulated by feeding the laboratory cultured rare minnow(Gobiocypris rarus) with field collected Limnodrilus sp. The results indicated that the food chain processes affected significantly the growth, slightly reduced gonadosomatic indices, and elevated hepatosomatic indices. There was an obvious vitellogenin(VTG) induction, which generally only occurred in mature female, in the serum of juvenile rare minnow and mature male when fed with Limnodrilus sp. In addition, the rare minnow feeding on Limnodrilus sp. had significantly high renal indices, it meant obvious renal hyperplasia. The present work suggested that. Limnodrilus sp. from field water may contain toxic pollutants and could lead to endocrine disruption effects to the predators. It was concluded that endocrine disruptors may not only be assimilated through water, but also be bioconcentrated through food web. The results also suggested the importance of food selection in conducting the study of endocrine disruption effects using sensitive species.

Endocrine effects of sublethal exposure to persistent organic pollutants (POPS) on silver carp (Hypophthalmichthys molitrix)

Silver carp (Hypophthalmichthys molitrix) samples were collected from five selected sites that represent diverse levels of downgraded persistent organic pollutants (POPs) contamination in Ya-Er Lake in October 1999. Hepatic ethoxyresorufin-O-deethylase (EROD) and UDP glucuronosyltransferase (UDPGT) activities, hepatosomatic index (HSI), hepatic retinoids, serum thyroid hormones were measured. It was found that hepatic retinol and serum free 3,5,3'- tetraiodothyronine (FT3) significantly increased (P < 0.01) when both hepatic EROD and UDPGT activities significantly declined (P < 0.01) from pond 1 to 5 with decrease in the degree of pollution. This significant negative correlation (P < 0.01) suggests that the persistent organochlorinated contaminants could induce hepatic EROD and UDPGT activities, alter retinoid and thyroid hormone homeostasis, and finally lead to the reduction of retinol and FT3, the two biologically active forms of retinoids and thyroid hormone in silver carp of Ya-Er Lake. (C) 2002 Elsevier Science Ltd. All rights reserved.