Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 17 de 17
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Int J Mol Sci ; 21(2)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936443

RESUMO

Wound healing is a very complex process that allows organisms to survive injuries. It is strictly regulated by a number of biochemical and physical factors, mechanical forces included. Studying wound healing in space is interesting for two main reasons: (i) defining tools, procedures, and protocols to manage serious wounds and burns eventually occurring in future long-lasting space exploration missions, without the possibility of timely medical evacuation to Earth; (ii) understanding the role of gravity and mechanical factors in the healing process and scarring, thus contributing to unravelling the mechanisms underlying the switching between perfect regeneration and imperfect repair with scarring. In the study presented here, a new in vivo sutured wound healing model in the leech (Hirudo medicinalis) has been used to evaluate the effect of unloading conditions on the healing process and the effectiveness of platelet rich plasma (PRP) as a countermeasure. The results reveal that microgravity caused a healing delay and structural alterations in the repair tissue, which were prevented by PRP treatment. Moreover, investigating the effects of microgravity and PRP on an in vitro wound healing model, it was found that PRP is able to counteract the microgravity-induced impairment in fibroblast migration to the wound site. This could be one of the mechanisms underlying the effectiveness of PRP in preventing healing impairment in unloading conditions.

2.
Sci Rep ; 8(1): 2267, 2018 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-29396513

RESUMO

Intraplaque release of inflammatory cytokines from macrophages is implicated in atherogenesis by inducing the proliferation and migration of media smooth muscle cells (SMCs). PCSK9 is present and released by SMCs within the atherosclerotic plaque but its function is still unknown. In the present study, we tested the hypothesis that PCSK9 could elicit a pro-inflammatory effect on macrophages. THP-1-derived macrophages and human primary macrophages were exposed to different concentrations (0.250 ÷ 2.5 µg/ml) of human recombinant PCSK9 (hPCSK9). After 24 h incubation with 2.5 µg/ml PCSK9, a significant induction of IL-1ß, IL-6, TNF-α, CXCL2, and MCP1 mRNA, were observed in both cell types. Co-culture of THP-1 macrophages with HepG2 overexpressing hPCSK9 also showed the induction of TNF-α (2.4 ± 0.5 fold) and IL-1ß (8.6 ± 1.8 fold) mRNA in macrophages. The effect of hPCSK9 on TNF-α mRNA in murine LDLR-/- bone marrow macrophages (BMM) was significantly impaired as compared to wild-type BMM (4.3 ± 1.6 fold vs 31.1 ± 6.1 fold for LDLR-/- and LDLR+/+, respectively). Finally, a positive correlation between PCSK9 and TNF-α plasma levels of healthy adult subjects (males 533, females 537) was observed (B = 8.73, 95%CI 7.54 ÷ 9.93, p < 0.001). Taken together, the present study provides evidence of a pro-inflammatory action of PCSK9 on macrophages, mainly dependent by the LDLR.


Assuntos
Citocinas/metabolismo , Macrófagos/imunologia , Pró-Proteína Convertase 9/metabolismo , Animais , Células Cultivadas , Técnicas de Cocultura , Feminino , Humanos , Masculino , Camundongos
3.
J Neurochem ; 141(2): 165-178, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28072455

RESUMO

Schwann cells' (SCs) development and maturation require coordinate and complementary activation of several signals and intracellular pathways. Among factors controlling these processes, the signalling intermediates Src tyrosine kinase and focal adhesion kinase (FAK) are relevant for SCs', participating in regulation of their adhesion, motility and migration. Recently, the progesterone metabolite allopregnanolone (ALLO) was proved to be synthesized by SCs, whereas it acts autocrinally on SCs motility and proliferation, which are crucial processes for nerve development, maturation and regeneration. Herein, we investigate the hypothesis that the molecular mechanisms behind the ALLO's action on SCs involve the signalling intermediates Src and FAK. We first demonstrated that ALLO 10-6  M regulates SCs morphology, motility and myelination, also increasing the internode distance in the in vitro myelination model of neuron/SCs co-culture. ALLO's actions were mediated by the modulation of Src/FAK pathway, since they were counteracted by PP2 10-5  M, a selective inhibitor of Src kinase. Then, we proved that Src/FAK activation in SCs involves GABA-A dependent mechanisms and actin re-arrangements. In conclusion, our findings are the first to corroborate the importance of the neuroactive steroid ALLO in regulating SCs development and maturation via the Src and phospho-FAK signalling activation. Cover Image for this issue: doi: 10.1111/jnc.13795.


Assuntos
Movimento Celular/fisiologia , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Fibras Nervosas Mielinizadas/enzimologia , Pregnanolona/farmacologia , Células de Schwann/enzimologia , Quinases da Família src/metabolismo , Animais , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Ratos , Células de Schwann/efeitos dos fármacos
4.
Neural Plast ; 2016: 5985021, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28090360

RESUMO

Memory is our ability to store and remember past experiences; it is the result of changes in neuronal circuits of specific brain areas as the hippocampus. During memory formation, neurons integrate their functions and increase the strength of their connections, so that synaptic plasticity is improved and consolidated. All these processes recruit several proteins at the synapses, whose expression is highly regulated by DNA methylation and histone tails posttranslational modifications. Steroids are known to influence memory process, and, among them, neurosteroids are implicated in neurodegenerative disease related to memory loss and cognitive impairment. The epigenetic control of neurosteroids involvement in memory formation and maintenance could represent the basis for neuroregenerative therapies.


Assuntos
Epigênese Genética/fisiologia , Hipocampo/fisiologia , Memória/fisiologia , Plasticidade Neuronal/fisiologia , Neurotransmissores/fisiologia , Animais , Epigênese Genética/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Humanos , Memória/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Neurotransmissores/farmacologia
5.
Pharmacol Res ; 103: 215-26, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26621245

RESUMO

The progression of prostate cancer (PC) to a metastatic hormone refractory disease is the major contributor to the overall cancer mortality in men, mainly because the conventional therapies are generally ineffective at this stage. Thus, other therapeutic options are needed as alternatives or in addition to the classic approaches to prevent or delay tumor progression. Catecholamines participate to the control of prostate cell functions by the activation of alpha1-adrenoreceptors (alpha1-AR) and increased sympathetic activity has been linked to PC development and evolution. Molecular and pharmacological studies identified three alpha1-AR subtypes (A, B and D), which differ in tissue distribution, cell signaling, pharmacology and physiological role. Within the prostate, alpha1A-ARs mainly control stromal cell functions, while alpha1B- and alpha1D- subtypes seem to modulate glandular epithelial cell growth. The possible direct contribution of alpha1D-ARs in tumor biology is supported by their overexpression in PC. The studies here presented investigate the "in vitro" antitumor action of A175, a selective alpha1D-AR antagonist we have recently obtained by modifying the potent, but not subtype-selective alpha1-AR antagonist (S)-WB4101, in the hormone-refractory PC3 and DU145 PC cell lines. The results indicate that A175 has an alpha1D-AR-mediated significant and dose-dependent antiproliferative action that possibly involves the induction of G0/G1 cell cycle arrest, but not apoptosis. In addition, A175 reduces cell migration and adhesiveness to culture plates. In conclusion, our work clarified some cellular aspects promoted by alpha1D-AR activity modulation and supports a further pharmacological approach in the cure of hormone-refractory PC, by targeting specifically this AR subtype.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/farmacologia , Benzofuranos/farmacologia , Citostáticos/farmacologia , Dioxanos/farmacologia , Receptores Adrenérgicos alfa 1/metabolismo , Apoptose , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Masculino , Neoplasias da Próstata , RNA Mensageiro/metabolismo , Receptores Adrenérgicos alfa 1/genética
6.
J Steroid Biochem Mol Biol ; 150: 64-85, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25766520

RESUMO

Memory formation and utilization is a complex process involving several brain structures in conjunction as the hippocampus, the amygdala and the adjacent cortical areas, usually defined as medial temporal lobe structures (MTL). The memory processes depend on the formation and modulation of synaptic connectivity affecting synaptic strength, synaptic plasticity and synaptic consolidation. The basic neurocognitive mechanisms of learning and memory are shortly recalled in the initial section of this paper. The effect of sex hormones (estrogens, androgens and progesterone) and of adrenocortical steroids on several aspects of memory processes are then analyzed on the basis of animal and human studies. A specific attention has been devoted to the different types of steroid receptors (membrane or nuclear) involved and on local metabolic transformations when required. The review is concluded by a short excursus on the steroid activated epigenetic mechanisms involved in memory formation.


Assuntos
Androgênios/metabolismo , Epigênese Genética/fisiologia , Estrogênios/metabolismo , Glucocorticoides/metabolismo , Memória/fisiologia , Progesterona/metabolismo , Tonsila do Cerebelo/fisiologia , Animais , Hipocampo/fisiologia , Humanos , Plasticidade Neuronal , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Sinapses/fisiologia , Lobo Temporal/fisiologia
7.
Cell Adh Migr ; 8(6): 595-602, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25482626

RESUMO

Platelet-rich plasma (PRP) is a platelet concentrate in a small volume of plasma. It is highly enriched in growth factors able to stimulate the migration and growth of bone-forming cells. PRP is often used in clinical applications, as dental surgery and fracture healing. Platelet derived growth factor (PDGF), is highly concentrated in PRP and it was shown in our previous studies to provide the chemotactic stimulus to SaOS-2 osteoblasts to move in a microchemotaxis assay. Aim of the present studies is to analyze the effects of a PRP pretreatment (short time course: 30-150 min) of SaOS-2 cells with PRP on the organization of actin cytoskeleton, the main effector of cell mobility. The results indicate that a pretreatment with PRP increases chemokinesis and chemotaxis and concomitantly induces the organization of actin microfilaments, visualized by immunocytochemistry, in a directionally elongated phenotype, which is characteristic of the cells able to move. PRP also produces a transient increase in the expression of PGDF α receptor. This reorganization is blocked by the immunoneutralization of PDGF demonstrating the responsibility of this growth factor in triggering the mechanisms responsible for cellular movements.


Assuntos
Citoesqueleto de Actina/fisiologia , Movimento Celular/fisiologia , Osteoblastos/fisiologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , Plasma Rico em Plaquetas , Citoesqueleto de Actina/ultraestrutura , Células Cultivadas , Quimiotaxia , Humanos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/ultraestrutura
8.
Biomed Res Int ; 2014: 368678, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25165701

RESUMO

Neuropathic pain arises as a direct consequence of a lesion or disease affecting the peripheral somatosensory system. It may be associated with allodynia and increased pain sensitivity. Few studies correlated neuropathic pain with nerve morphology and myelin proteins expression. Our aim was to test if neuropathic pain is related to nerve degeneration, speculating whether the modulation of peripheral GABA-B receptors may promote nerve regeneration and decrease neuropathic pain. We used the partial sciatic ligation- (PSL-) induced neuropathic model. The biochemical, morphological, and behavioural outcomes of sciatic nerve were analysed following GABA-B ligands treatments. Simultaneous 7-days coadministration of baclofen (10 mg/kg) and CGP56433 (3 mg/kg) alters tactile hypersensitivity. Concomitantly, specific changes of peripheral nerve morphology, nerve structure, and myelin proteins (P0 and PMP22) expression were observed. Nerve macrophage recruitment decreased and step coordination was improved. The PSL-induced changes in nociception correlate with altered nerve morphology and myelin protein expression. Peripheral synergic effects, via GABA-B receptor activation, promote nerve regeneration and likely ameliorate neuropathic pain.


Assuntos
Regeneração Nervosa , Neuralgia/tratamento farmacológico , Neuropatia Ciática/tratamento farmacológico , Ácido gama-Aminobutírico/metabolismo , Animais , Baclofeno/administração & dosagem , Expressão Gênica , Humanos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Ligantes , Proteínas da Mielina/biossíntese , Bainha de Mielina/genética , Bainha de Mielina/metabolismo , Neuralgia/fisiopatologia , Ratos , Nervo Isquiático/metabolismo , Nervo Isquiático/fisiopatologia , Neuropatia Ciática/fisiopatologia
9.
Biomed Res Int ; 2014: 801473, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24877132

RESUMO

Prostate cancer (PC) progression from androgen-dependent (AD) to castration-resistant (CR) disease is a process caused by modifications of different signal transduction pathways within tumor microenvironment. Reducing cell proliferation, estrogen receptor beta (ERbeta) is emerging as a potential target in PC chemoprevention. Among the known selective ERbeta ligands, 3beta-Adiol, the endogenous ligand in the prostate, has been proved to counteract PC progression. This study compares the effects of chronic exposure (1-12 weeks) to different ERbeta selective ligands (DPN, 8beta-VE2, 3beta-Adiol) on proliferation of human androgen-responsive CWR22Rv1 cells, representing an intermediate phenotype between the AD- and CR-PC. 3beta-Adiol (10 nM) is the sole ligand decreasing cell proliferation and increasing p21 levels. In vitro transcriptional activity assays were performed to elucidate different behavior between 3beta-Adiol and the other ligands; in these experiments the endogenous and the main ERbeta subtype activation were considered. It is concluded that ERbeta activation has positive effects also in androgen-responsive PC. The underlying mechanisms are still to be clarified and may include the interplay among different ERbeta subtypes and the specific PC microenvironment. ERbeta agonists might be useful in counteracting PC progression, although the final outcome may depend upon the molecular pattern specific to each PC lesion.


Assuntos
Androstano-3,17-diol/análogos & derivados , Androstano-3,17-diol/farmacologia , Receptor beta de Estrogênio/agonistas , Neoplasias da Próstata/tratamento farmacológico , Receptores Androgênicos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Receptor beta de Estrogênio/metabolismo , Células HEK293 , Humanos , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
10.
Environ Toxicol ; 29(8): 856-66, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22987612

RESUMO

Perinatal polychlorinated biphenyl (PCB) exposures still remain a serious health concern because offspring receive PCB burden from mother during vulnerable processes of development. Since cytochrome P450 (CYP) represents a toxicological endpoint, in the present study, representing an extended investigation of a previous multitasked one, we explored the long-term responsiveness of CYP1A and CYP2B isoforms by Western blot analysis in liver and whole brain of lactating (PN12), weaning (PN21), and adult offspring (PN60) rats prenatally and lactationally exposed to a reconstituted PCB mixture (RM) of noncoplanar PCB138, 153, 180, and coplanar PCB126 congeners. We chose highly chlorinated PCBs instead of lower chlorinated one, because their recalcitrance to biotransformation makes easy their accumulation/persistence in tissues and breast milk. Dioxin-like congener PCB126 binding aryl hydrocarbon receptor (AHR) is responsible of many toxic effects. Pregnant Sprague-Dawley dams with high affinity AHR received subcutaneous injection of RM (10 mg/kg body weight) daily during gestation (days 15-19) and twice a week during breast-feeding. The results evidenced a transfer of PCBs to neonates through milk and a significant responsiveness of hepatic CYP in both mothers and offspring. In liver of exposed progeny, CYP isoforms exhibited a significant increment at PN12 (70% over control) and at PN21 (270% over control). Contrary to dams, in adult PCB offspring CYP levels showed a decline up to values similar to those of control. This transient developmental responsiveness of CYP isoforms in offspring liver reflects roughly the time course of hepatic PCB levels previously reported. Even if congeners were detected in brain, we failed in evidencing a responsiveness of CYP isoforms probably because of region-specific CYP expression in this organ. In conclusion, induction of offspring hepatic CYP is index of liver PCB burden, and despite the insensitivity of whole brain CYP we cannot exclude brain vulnerability toward PCB. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 856-866, 2014.


Assuntos
Encéfalo/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Poluentes Ambientais/toxicidade , Lactação/metabolismo , Fígado/metabolismo , Bifenilos Policlorados/toxicidade , Animais , Animais Recém-Nascidos , Citocromo P-450 CYP1A1/metabolismo , Poluentes Ambientais/metabolismo , Feminino , Isoenzimas/metabolismo , Masculino , Exposição Materna , Leite/metabolismo , Oxirredução , Bifenilos Policlorados/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos Sprague-Dawley , Receptores de Hidrocarboneto Arílico/metabolismo , Distribuição Tecidual
11.
Epigenomics ; 4(1): 101-12, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22332662

RESUMO

BACKGROUND: The epigenome represents an important target of environmental pollution. Early-life exposure to polychlorinated biphenyls (PCBs) modifies sex steroid enzymes and receptor transcription patterns. Steroid receptors, such as androgen receptor (AR), function as coregulators of histone modification enzymes. AIM: To clarify if a PCB early-life exposure might affect the epigenome in rat liver, we analyzed some histone post-translational modifications (H3K4me3 and H4K16Ac) and the corresponding histone remodeling enzymes, and the AR as a histone enzyme coregulator. RESULTS: We observed a decrease of H4K16Ac and H3K4me3 levels, possibly linked to the induction of chromatin-modifying enzymes SirtT1 and Jarid1b, and a decrease of AR. PCBs also seem to induce AR transcriptional activity. Some of the observed effects are sex dimorphic. CONCLUSION: Our data suggest that an early-life exposure to PCB sometimes modifies the epigenome in the offspring liver in a dimorphic way. AR might be involved in modulating PCB effects on the epigenome.


Assuntos
Poluentes Ambientais/toxicidade , Histonas/metabolismo , Fígado/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Animais , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Feminino , Células HEK293 , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Fígado/metabolismo , Masculino , Metilação , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Ratos , Ratos Sprague-Dawley , Sirtuína 1/genética , Sirtuína 1/metabolismo , Transcrição Genética
12.
Brasília méd ; 47(2)ago. 2010. ilus
Artigo em Português | LILACS-Express | ID: lil-565123

RESUMO

Epigenética representa a programação do genoma para expressar o conjunto apropriado de genes em células específicas em momentos específicos da vida. Os principais mecanismos epigenéticos são: 1 - metilação de citosinas nas ilhas CpG localizadas na região promotorade vários genes; 2 - acetilação pós-translacional ou metilação de lisinas na região N-terminal da histona, que influencia a cobertura da cromatina; e, 3 - produção de micro-RNAs não codificantes envolvidos na modulação da expressão gênica. Epigenética inclui mudanças hereditárias na atividade e expressão do gene, mas também alterações estáveis em longo prazo no potencial de transcrição de uma célula que não é necessariamente hereditária. Essas mudanças podem ser produzidas em especial pelo ambiente no início da vida (poluição, infecção, cuidadosmaternos, etc) e pode afetar a saúde na vida adulta, influenciando a susceptibilidade a diversas doenças, como câncer, psiquiátricas ou neurológicas. Ferramentas farmacológicas e outras formas de intervenção podem modificar potencialmente o padrão epigenético natural, oferecendo um caminho possível para reverter a programação epigenéticadeletéria.


Epigenetic represents the programming of the genome to express the appropriate set of genes in specific cells at specific time points in life. The main epigenetic mechanisms are: 1 - methylation status of cytosines within CpG islands located in the promoter region of many genes; 2 - post-translational acetylation or methylation of lysines in the histone N-terminal region, which influence chromatin packaging; and 3 - production of non coding micro-RNAs involved in gene expression modulation. Epigenetic includes both heritable changes in gene activity and expressionbut also stable, long-term alterations in the transcriptional potential of a cell that are not necessarily heritable. These changes might be produced in particular by the early life environment (pollution, infection, maternal care, etc) and might affect health in adult life influencing the susceptibility to several diseases, such as cancer, psychiatric or neurologicaldisorders.

13.
Toxicol Appl Pharmacol ; 237(2): 127-36, 2009 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-19327374

RESUMO

Polychlorinated biphenyls (PCBs) are pollutants detected in animal tissues and breast milk. The experiments described in the present paper were aimed at evaluating whether the four PCB congeners most abundant in animal tissues (PCB-138, -153, -180 and -126), administered since fetal life till weaning, can induce long-term alterations of GH-axis activity and bone mass in the adult rat. We measured PCB accumulation in rat brain and liver, somatic growth, pituitary GH expression and plasma hormone concentrations at different ages. Finally, we studied hypothalamic somatostatin expression and bone structure in adulthood, following long-term PCB exposure. Dams were treated during pregnancy from GD15 to GD19 and during breast-feeding. A constant reduction of the growth rate in both male and female offspring from weaning to adulthood was observed in exposed animals. Long-lasting alterations on hypothalamic-pituitary GH axis were indeed observed in PCB-exposed rats in adulthood: increased somatostatin expression in hypothalamic periventricular nucleus (both males and females) and lateral arcuate nucleus (males, only) and decreased GH mRNA levels in the pituitary of male rats. Plasma IGF-1 levels were higher in PCB-exposed male and female animals as compared with controls at weaning and tended to be higher at PN60. Plasma testosterone and thyroid hormone concentrations were not significantly affected by exposure to PCBs. In adulthood, PCBs caused a significant reduction of bone mineral content and cortical bone thickness of tibiae in male rat joint to increased width of the epiphyseal cartilage disk. In conclusion, the developmental exposure to the four selected PCB compounds used in the present study induced far-reaching effects in the adult offspring, the male rats appearing more sensitive than females.


Assuntos
Densidade Óssea/efeitos dos fármacos , Bifenilos Policlorados/administração & dosagem , Bifenilos Policlorados/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Encéfalo/metabolismo , Química Encefálica , Poluentes Ambientais/administração & dosagem , Poluentes Ambientais/química , Poluentes Ambientais/toxicidade , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/genética , Hormônio do Crescimento/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Fígado/química , Fígado/metabolismo , Masculino , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Bifenilos Policlorados/química , Gravidez , Ratos , Somatostatina/metabolismo , Hormônios Tireóideos/sangue
14.
Int J Biomed Sci ; 5(4): 380-9, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23675162

RESUMO

PDGF is a major constituent of platelet rich plasma (PRP), responsible of chemotactic and possibly of mitogenic effects of PRP on osteoblasts. PDGF family includes 5 isoforms: PDGF-AA, PDGF-AB, PDGF-BB, PDGF-CC and PDGF-DD, all expressed in platelets except PDGF-DD. Aim of this study was to analyze the effect of recombinant hPDGF-A, -AB, -B and -C, on migration and proliferation of a human osteoblastic cell line, SaOS-2. Preliminary observations on cell migration were also done in primary cultures of human osteoblasts. In vitro microchemotaxis and (3)H-thymidine mitogenic assays were used. While PDGF-AB is active at concentrations present in PRP, PDGF-AA and BB are chemotactic only at much higher doses. PDGF-C is totally inactive alone or together with the active isoforms. PDGF-AA, PDGF-BB and PDGF-C stimulate SaOS-2 proliferation only at the highest dose tested, while PDGF-AB is ineffective. Primary osteoblasts are less sensitive than SaOS-2 and progressively lose responsiveness with increasing passages in culture, in line with loss of cell differentiation. The different PDGF isoforms act differentially on osteoblasts, the-AB isoform appearing the major responsible of the PRP chemiotaxis. PDGF, at the concentrations present in PRP, does not affect cell proliferation.

15.
J Steroid Biochem Mol Biol ; 109(3-5): 294-9, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18403198

RESUMO

Brain sexual differentiation is a complex developmental phenomenon influenced by the genetic background, sex hormone secretions and environmental inputs, including pollution. The main hormonal drive to masculinize and defeminize the rodent brain is testosterone secreted by the testis. The hormone does not influence sex brain differentiation only in its native configuration, but it mostly needs local conversion into active metabolites (estradiol and DHT) through the action of specific enzymatic systems: the aromatase and 5alpha-reductase (5alpha-R), respectively. This allows the hormone to control target cell gene expression either through the estrogen (ER) or the androgen (AR) receptors. The developmental profile of testosterone metabolizing enzymes, different in the two sexes, is therefore of the utmost importance in affecting the bioavailability of the steroids active in brain differentiation. Widely diffused pollutants, like polychlorinated biphenyls (PCBs) are able to affect the production and/or action of testosterone metabolites, exerting detrimental influences on reproduction and sex behavior. The main studies performed in our and other laboratories concerning the pattern of expression and the control of the enzymatic systems involved in brain androgen action and metabolism are shortly reviewed. Some recent data on the influence exerted by PCBs on these metabolic systems are also reported.


Assuntos
Meio Ambiente , Hormônios/metabolismo , Hipotálamo/citologia , Hipotálamo/metabolismo , Roedores/metabolismo , Diferenciação Sexual , Animais , Poluentes Ambientais , Humanos
16.
Reprod Toxicol ; 20(4): 521-30, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15869859

RESUMO

Interaction of polychlorinated biphenyls (PCBs) with the aryl hydrocarbon receptor (AhR)/nuclear translocator (ARNT) system might interfere with the mechanisms controlling the sexual differentiation of the developing hypothalamus. The aim of this study was to evaluate the presence of AhR/ARNT in brain cells and the developmental profile of their expression in the hypothalamus of male and female rats during the perinatal period. Brain accumulation of the main PCB congeners after prenatal exposure to Aroclor 1254 and its influence on hypothalamic expression of AhR/ARNT was also assessed. The results show that: (a) AhR and ARNT are expressed both in neurons and in glia; (b) AhR expression progressively increases in the developing hypothalamus particularly in males, while ARNT is relatively constant in both sexes; (c) the prenatal administration of Aroclor to dams produces a differential accumulation of PCBs, depending on the chlorine atom number, and stimulates AhR expression only in the male hypothalamus. In conclusion, the developing male hypothalamus might be more sensitive to disrupting potential of PCBs.


Assuntos
Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Hipotálamo/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Receptores de Hidrocarboneto Arílico/metabolismo , Diferenciação Sexual/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Translocador Nuclear Receptor Aril Hidrocarboneto/biossíntese , Células Cultivadas , Feminino , Idade Gestacional , Hipotálamo/embriologia , Hipotálamo/metabolismo , Masculino , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Receptores de Hidrocarboneto Arílico/biossíntese , Fatores Sexuais
17.
Brasília méd ; 41(1/4): 49-59, 2004. ilus, tab
Artigo em Português | LILACS | ID: lil-430552

RESUMO

As diferenças existentes entre machos e fêmeas na morfologia e nas modalidades de funcionamento de numerosos núcleos cerebrais são determinadas, em grande parte, pelo ambiente hormonal presente durante o desenvolvimento embrionário. Os hormônios esteróides, em modo particular a testosterona, desenvolvem um papel crucial na masculinização dos centros cerebrais que governarão a secreção de vários hormônios hipotalâmicos e hipofisários, o comportamento sexual e a capacidade de aprendizagem e de memorização do indivíduo adulto. Nos últimos anos, surgiram dois aspectos importantes em relação ao mecanismo de ação da testosterona: 1) sua conversão, diretamente em nível de células-alvo, em compostos em grau de amplificar ou diversificar sua ação; 2) a presença, no sistema nervoso central (em particular no hipotálamo), da 5-alfa-redutase e da aromatase, enzimas necessárias a tais transformações. A interação dos metabólitos ativos resultantes (respectivamente, diidrotestosterona e estradiol) com específicos receptores intracelulares induz a transcrição de genes que determinam a diferenciação, em sentido masculino, das estruturas cerebrais em via de desenvolvimento. Nesta breve revisão, descrevem-se os conhecimentos atuais das principais características das duas vias enzimáticas que medeiam efeitos de diferenciação dos androgênios sobre o cérebro embrionário. Particular atenção é direcionada à discussão dos dados experimentais, obtidos principalmente nos roedores, em relação aos efeitos dos estrogênios de origem androgênica sobre a diferenciação sexual do cérebro. Discute-se também o papel co-primário que o genótipo desenvolve na diferenciação dimórfica do cérebro. Por fim, aborda-se a possível influência dos metabólitos ativos da testosterona sobre a diferenciação sexual do cérebro humano à luz de algumas doenças que comportam desequilíbrio nos níveis normais ou no mecanismo de ação dos hormônios gonadais durante o desenvolvimento embrionário.


Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase , Androgênios , Aromatase , Homossexualidade , Diferenciação Sexual
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA