Ovariectomy of female SHR blunted ACh and ISO dilatory responses. ISO dose-response curves were Nec-1s shifted to the left in castrated male SHR.\n\nConclusions: Gonadectomy exerts long-term effects on mesenteric vascular reactivity and hypertension in the SHR.”
“Background: Heat shock protein 70 (HSP70) protects inner ear cells from damage and death induced by e. g. heat or toxins. Benzoquinone ansamycin antibiotic geldanamycin (GA) was demonstrated to induce the expression of HSP70 in various animal cell types. The

aim of our study was to investigate whether GA induces HSP70 in the organ of Corti (OC), which contains the auditory sensory cells, and whether GA can protect these cells from toxicity

caused by a common aminoglycoside antibiotic gentamicin.\n\nMethods: To address these questions, we used the OC explants isolated from p3-p5 rats. As a read-out, we used RT-PCR, ELISA and immunofluorescence.\n\nResults: We found that GA at the concentration of 2 mu M efficiently induced HSP70 expression on mRNA and protein level in the OC explants. Confocal microscopy revealed that HSP70 induced by GA is expressed by hair cells and interdental cells of spiral limbus. Preincubation of explants with 2 mu M GA prior to adding gentamicin (500 mu M) significantly reduced the loss of Pitavastatin clinical trial outer but not inner hair cells, suggesting different mechanisms of otoprotection needed for these two cell types.\n\nConclusion: GA induced HSP70 in the auditory sensory cells and partially protected them from

toxicity of gentamicin. Understanding the molecular mechanisms of GA otoprotection may provide insights for preventative therapy of the hearing loss caused by aminoglycoside antibiotics.”
“NEDD8 (neural precursor cell expressed, developmentally down-regulated 8) is a ubiquitin-like molecule whose action on modifying protein substrates is critical in various cellular functions but whose importance in the immune system is not well understood. Here we investigated the role of protein neddylation in regulating T-cell function using an in vivo knockdown technique. We found that reduced expression of Ubc12 in CD4(+) T cells led to impaired T-cell receptor/CD28-induced proliferation and cytokine production both see more in vitro and in vivo, accompanied by reduced Erk activation. These findings were recapitulated by treatment with MLN4924, an inhibitor of NEDD8-activating enzyme. Furthermore, Shc, an adaptor molecule between antigen receptors and the Ras/Erk pathway, was identified as a target for neddylation. Importantly, mice adoptively transferred with Ubc12 knockdown CD4(+) T cells showed markedly ameliorated allergic responses. This study thus identifies an important role for protein neddylation in T-cell function, which may serve as a therapeutic target for inflammatory diseases.