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GABAA receptor dephosphorylation followed by internalization is coupled to neur...

Mele, Miranda; Ribeiro, Luís; Inácio, Ana R.; Wieloch, Tadeusz; Duarte, C. B.

Cerebral ischemia is characterized by an early disruption of GABAergic neurotransmission contributing to an imbalance of the excitatory/inhibitory equilibriumand neuronal death, but the molecular mechanisms involved are not fully understood. Here we report a downregulation of GABAA receptor (GABAAR) expression, affecting both mRNA and protein levels of GABAAR subunits, in hippocampal neurons subjected to oxygen...


Regulation of AMPA receptors and synaptic plasticity

Santos, S. D.; Carvalho, A. L.; Caldeira, M. V.; Duarte, C. B.

Neuronal activity controls the strength of excitatory synapses by mechanisms that include changes in the postsynaptic responses mediated by AMPA receptors. These receptors account for most fast responses at excitatory synapses of the CNS, and their activity is regulated by various signaling pathways which control the electrophysiological properties of AMPA receptors and their interaction with numerous intracell...


Role of the brain-derived neurotrophic factor at glutamatergic synapses

Carvalho, A. L.; Caldeira, M. V.; Santos, S. D.; Duarte, C. B.

The neurotrophin brain-derived neurotrophic factor (BDNF) plays an important role in the activity-dependent regulation of synaptic structure and function, particularly of the glutamatergic synapses. BDNF may be released in the mature form, which activates preferentially TrkB receptors, or as proBDNF, which is coupled to the stimulation of the p75(NTR). In the mature form BDNF induces rapid effects on glutamate ...


Effect of Skin Sensitizers on Inducible Nitric Oxide Synthase Expression and Ni...

Cruz, M. T.; Neves, B. M.; Gonçalo, M.; Figueiredo, A.; Duarte, C. B.; Lopes, M. C.

Nitric oxide (NO) is involved in the pathogenesis of acute and chronic inflammatory conditions, namely in allergic contact dermatitis (ACD). However, the mechanism by which NO acts in ACD remains elusive. The present study focuses on the effects of different contact sensitizers (2,4-dinitrofluorbenzene, 1,4-phenylenediamine, nickel sulfate), the inactive analogue of DNFB, 2,4-dichloronitrobenzene, and two irrit...


Excitotoxicity mediated by Ca2+-permeable GluR4-containing AMPA receptors invol...

Santos, A. E.; Duarte, C. B.; Iizuka, M.; Barsoumian, E. L.; Ham, J.; Lopes, M. C.; Carvalho, A. P.; Carvalho, A. L.

Cells preferentially expressing GluR4-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors are particularly sensitive to excitotoxicity mediated through non-N-methyl-D-aspartate receptors. However, the excitotoxic signalling pathways associated with GluR4-containing AMPA receptors are not known. In this work, we investigated the downstream signals coupled to excitotoxicity media...


Neuroprotection by BDNF against glutamate-induced apoptotic cell death is media...

Almeida, R. D.; Manadas, B. J.; Melo, C. V.; Gomes, J. R.; Mendes, C. S.; Grãos, M. M.; Carvalho, R. F.; Carvalho, A. P.; Duarte, C. B.

Neurotrophins protect neurons against glutamate excitotoxicity, but the signaling mechanisms have not been fully elucidated. We studied the role of the phosphatidylinositol 3-kinase (PI3-K) and Ras/mitogen-activated protein kinase (MAPK) pathways in the protection of cultured hippocampal neurons from glutamate induced apoptotic cell death, characterized by nuclear condensation and activation of caspase-3-like e...


Contact sensitizers downregulate the expression of the chemokine receptors CCR6...

Cruz, M. T.; Gonçalo, M.; Paiva, A.; Morgado, J. M.; Figueiredo, A.; Duarte, C. B.; Lopes, M. C.

Chemokines are involved in the control of dendritic cell (DC) trafficking, which is critical for the immune response, namely in allergic contact dermatitis (ACD). In this work, we investigated by flow cytometry the effect of the contact sensitizers 2,4-dinitrofluorobenzene (DNFB), 1,4-phenylenediamine (PPD) and nickel sulfate (NiSO4), on the surface expression of the chemokine receptors CCR6 and CXCR4 in DC. As...


Intracellular lithium and cyclic AMP levels are mutually regulated in neuronal ...

Montezinho, L. P.; Duarte, C. B.; Fonseca, C. P.; Glinka, Y.; Layden, B.; Freitas, D. Mota de; Geraldes, C. F. G. C.; Castro, M. M. C. A.

In this work, we studied the effect of intracellular 3',5'-cyclic adenosine monophosphate (cAMP) on Li+ transport in SH-SY5Y cells. The cells were stimulated with forskolin, an adenylate cyclase activator, or with the cAMP analogue, dibutyryl-cAMP. It was observed that under forskolin stimulation both the Li+ influx rate constant and the Li+ accumulation in these cells were increased. Dibutyryl-cAMP also increa...


Dexamethasone prevents interleukin-1beta-induced nuclear factor-kappaB activati...

Castro-Caldas, M.; Mendes, A. F.; Carvalho, A. P.; Duarte, C. B.; Lopes, M. C.

AIMS: Glucocorticoids (GCs) exert some of their anti-inflammatory actions by preventing the activation of the transcription factor nuclear factor (NF)-kappaB. The GC-dependent inhibition of NF-kappaB may occur at different levels, but the mechanisms involved are still incompletely understood. In this work, we investigated whether the synthetic GC, dexamethasone (Dex), modulates the activity of NF-kappaB in the ...


Dexamethasone-induced and estradiol-induced CREB activation and annexin 1 expre...

Castro-Caldas, M.; Mendes, A. F.; Duarte, C. B.; Lopes, M. C. F.

AIMS: Annexin 1 (ANXA1), a member of the annexin family of calcium-binding and phospholipid-binding proteins, is a key mediator of the anti-inflammatory actions of steroid hormones. We have previously demonstrated that, in the human lymphoblastic CCRF-CEM cell line, both the synthetic glucocorticoid hormone, dexamethasone (Dex), and the estrogen hormone, 17beta-estradiol (E2beta), induce the synthesis of ANXA1,...


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    Financiadores do RCAAP

Fundação para a Ciência e a Tecnologia Universidade do Minho   Governo Português Ministério da Educação e Ciência Programa Operacional da Sociedade do Conhecimento União Europeia