Endogenous annexin A1 counter-regulates bleomycin-induced lung fibrosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

In vitro and in vivo studies on CCR10 regulation by Annexin A1

The mode of action of annexin A1 (ANXA1) is poorly understood. By using rapid subtraction hybridization we studied the effects of human recombinant ANXA1 and the N-terminal ANXA1 peptide on gene expression in a human larynx cell line. Three genes showed strong downregulation after treatment with ANXA1. In contrast, expression of CCR10, a seven transmembrane G-protein coupled receptor for chemokine CCL27 involved in mucosal immunity, was increased. Moreover the reduction in CCR10 expression induced by ANXA1 gene deletion was rescued by intravenous treatment with low doses of ANXA1. These findings provide new evidence that ANXA1 modulates gene expression. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Influence of N-Terminus Modifications on the Biological Activity, Membrane Interaction, and Secondary Structure of the Antimicrobial Peptide Hylin-a1

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hylin a1, the first cytolytic peptide isolated from the arboreal South American frog Hypsiboas albopunctatus ('spotted treefrog')

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Morphometric and quantitative characterization of atrial ganglion neurons from the intercaval region in dogs with dilated cardiomyopathy

Avaliaram-se quantitativa, morfométrica e qualitativamente os neurônios atriais da faixa intercaval de cães com cardiomiopatia dilatada (CMD). Os neurônios dos gânglios nervosos de cães com CMD eram maiores que os dos cães controle. A histopatologia do miocárdio ventricular e dos neurônios ganglionares confirmou a CMD e demonstrou evidente processo degenerativo neuronal ganglionar. Cães com CMD em fase crônica apresentavam cardioneuropatia secundária, provavelmente pela privação da inervação parassimpática cardíaca.

THE EFFECT OF TUBEROINFUNDIBULAR DOPAMINERGIC-NEURONS ON PROLACTIN AND ALPHA-MELANOCYTE STIMULATING HORMONE-RELEASE

The effect of tubero-infundibular dopaminergic neurons (TIDA) on the release of prolactin (PRL) and alpha-melanocyte stimulating hormone (alpha-MSH) was studied in median eminence-lesioned (MEL) male rats (N = 6-28). Plasma PRL and alpha-MSH levels were significantly elevated 2 (86.1 +/- 19.8 and 505.1 +/- 19.1 ng/ml), 4 (278.7 +/- 15.5 and 487.4 +/- 125.1 ng/ml), 7 (116.2 +/- 16.2 and 495.8 +/- 62.6 ng/ml) and 14 (247.3 +/- 26.1 and 448.4 +/- 63.8 ng/ml) days after MEL when compared to sham-operated control animals (55.5 +/- 13.4 and 56.2 +/- 6.1 ng/ml, respectively). MEL altered plasma PRL and alpha-MSH levels in a differential manner, with a 1.5-to 5.0-fold increase in PRL and an 8.0-to 9.0-fold increase in alpha-MSH. The increase of alpha-MSH levels occurred abruptly and remained constant from days 2 to 14. These observations indicate that TIDA plays an important role in the pituitary release of PRL and alpha-MSH and provide evidence that the release of the two hormones occurs in a differential manner.

Acute swimming stress induces changes in noradrenergic mechanisms in order to maintain the response pattern of the rat vas deferens to norepinephrine

This study investigated mechanisms involved in the maintenance of the functional response pattern of the postjunctional alpha(1)-adrenoceptor in vas deferens isolated from rats submitted to acute swimming stress. The plasma corticosterone levels increased approximately three times after the swimming stress in the nontreated rats as well as after swimming stress in the rats pretreated with desipramine (DMI), yohimbine (YO), or DMI with YO. No alteration was detected in the sensitivity to norepinephrine (NE) in the vasa deferentia from the stressed rats or stressed rats treated with DMI or DMI with YO, in relation to their respective control. However, when the vasa deferentia were previously incubated with DMI, a reduction in sensitivity to NE in organs from stressed rats was observed. Vasa deferentia excised from rats pretreated with YO before the swimming stress showed an increase in postjunctional alpha(1)-response that was abolished by prazosin (PZ). Thus, the neuronal uptake, the prejunctional alpha(2)-adrenoceptors (mediating prejunctional inhibition), the occupancy and functional response of the postjunctional alpha(1)-adrenoceptors, and the emotional stress component were very important for the determination of the noradrenergic response pattern in vas deferens from rats submitted to acute swimming stress. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

Noradrenergic response in vas deferens from rats submitted to acute and repeated stress

1. This work investigated the effects of androgens on the norepinephrine sensitivity of vasa deferentia from rats submitted to acute or repeated stress, as well as the participation of alpha(1)-adrenoceptors in the response of intact and bisected vasa deferentia from adult normal rats submitted to acute or repeated stress.2. The acute stress produced subsensitivity to norepinephrine only in intact vasa deferentia from adult normal rats, which was prevented by lack of androgens, suggesting that the sensitivity may be dependent on the physiological level of androgen,3. No change was observed in intact vas deferens sensitivity to norepinephrine in repeated stress, suggesting the occurrence of adaptation to elevated norepinephrine levels or a mild decrease in androgen levers or both.4. The changes in sensitivity observed in acute and repeated stress may also be due to alterations in alpha(1)-adrenergic receptors that are located in the prostatic portion of the vas deferens. (C) 1998 Elsevier B.V.

The antiepileptic activity of JSTX-3 is mediated by N-methyl-D-aspartate receptors in human hippocampal neurons

We analyzed the effect of the acylpolyaminetoxin JSTX-3 on the epileptogenic discharges induced by perfusion of human hippocampal slices with artificial cerebrospinal fluid lacking Mg2+ or N-methyl-D-aspartate. Hippocampi were surgically removed from patients with refractory medial temporal lobe epilepsy, sliced in the surgical room and taken to the laboratory immersed in normal artificial cerebrospinal fluid. Epileptiform activity was induced by perfusion with Mg2+-free artificial cerebrospinal fluid or by iontophoretically applied N-methyl-D-aspartate and intracellular and field recordings of CAI neurons were performed. The ictal-like discharges induced by Mg2+-free artificial cerebrospinal fluid and N-methyl-D-aspartate were blocked by incubation with JSTX-3. This effect was similar to that obtained with the N-methyl-D-aspartate receptor antagonist DL(-)2-amino-5 phosphonovaleric acid. Our findings suggest that in human hippocampal neurons, the antiepileptic effect of JSTX-3 is mediated by its action on N-methyl-D-aspartate receptor.

Annexin-A1 gene expression during liver development and post-translation modification after experimental endotoxemia

Objective and design: We have previously reported a role for annexin-A1 in liver proliferation and tumorogenicity as well as its action as an acute phase protein in a model of endotoxemia in interleukin-6 null mice.Material and methods: In this study, we have investigated the analysis of the gene and protein expression in annexin-A1 null mice and the wild type livers during foetal and adult life, and in the presence of a proinflammatory stimulus.Results: The data indicate a link between the expression of the annexin-A1 as serine-phosphorylated-protein during early events of the inflammatory response and as tyrosine-phosphorylated-form at later time-points, during the resolution of inflammation.Conclusions: The study of annexin-A1 post-translation modification may promote a new annexin-A1 peptide discovery programme to treat specific pathologies.

The impact of endogenous annexin A1 on glucocorticoid control of in ammatory arthritis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)