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“In brainstem slices of young male rat, we investigated the influence of the neuroactive steroid testosterone (T) on the synaptic responses by analyzing the field potential evoked in the medial vestibular nucleus (MVN) by vestibular afferent stimulation.

T induced three distinct and independent long-term synaptic changes: fast long-lasting potentiation (fLP), slow long-lasting potentiation (sLP) and long-lasting depression (LD). The fLP was mediated by 17 beta-estradiol (E-2) Selleckchem CP868596 since it was abolished by blocking the estrogen receptors (ERs) or the enzyme converting T to E-2. Conversely, sLP and LD were mediated by 5 alpha-dihydrotestosterone (DHT) since they were prevented by blocking the androgen receptors (ARs) or the enzyme converting T to DHT. Therefore, the synaptic effects of T were mediated by its androgenic or estrogenic metabolites. The pathways leading to estrogenic and androgenic conversion of T might be co-localized since, the occurrence of fLP under block of androgenic pathway, and that of sLP and LD under estrogenic block, were higher than those observed without blocks. In case of co-localization,

the effect on synaptic transmission should depend on the prevailing enzymatic activity. We conclude that circulating and neuronal T can remarkably influence synaptic responses of the GSI-IX vestibular neurons in different and opposite ways, depending on its conversion to estrogenic or androgenic metabolites. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Epstein-Barr Virus (EBV) latent membrane protein 1 (LMP1) is required for EBV B-lymphocyte transformation, transforms rodent fibroblasts, and can induce lymphoma and epithelial

hyperplasia in transgenic mice. Two domains have been identified BCKDHA within the intracellular carboxy terminus that can activate NF-kappa B, C-terminus-activating region 1 (CTAR1) and CTAR2, through interactions with tumor necrosis receptor-associated factors (TRAFs). CTAR1 can activate both the canonical and noncanonical NF-kappa B pathways and has unique effects on cellular gene expression. The epidermal growth factor receptor (EGFR) is highly induced by LMP1-CTAR1 in epithelial cells through activation of a novel NF-kappa B form containing p50 homodimers and Bcl-3. To further understand the regulation of NF-kappa B in CTAR1-induced EGFR expression, we evaluated the ability of CTAR1 to induce EGFR in mouse embryonic fibroblasts (MEFs) defective for different NF-kappa B effectors. CTAR1-mediated EGFR induction required the NF-kappa B-inducing kinase (NIK) but not the I kappa B kinase (IKK) complex components that regulate canonical or noncanonical NF-kappa B pathways. CTAR1-mediated induction of nuclear p50 occurred in IKK beta-, IKK gamma-, and NIK-defective MEFs, indicating that this induction is not dependent on the canonical or noncanonical NF-kappa B pathways. EGFR and nuclear p50 were expressed at high levels in TRAF2(-/-) fibroblasts and were not induced by CTAR1.