“
“Heat shock proteins (HSPs) are potent protectors of cellular integrity against environmental stresses, including toxic microbial products. To investigate the mechanism of HSP-70 cell protection against bacterial lipopolysaccharide click here (LPS), we established a stable HSP-70 gene-transfected RAW 264.7 murine macrophage model of LPS-induced cell death. Bacterial LPS increases the activity of sphingosine kinase 1 (SK1), which catalyzes formation of sphingosine-1-phosphate (S1p). S1P functions as a critical signal

for initiation and maintenance of diverse aspects of immune cell activation and function. When mouse macrophages were incubated with Escherichia coli LPS (1 mu g/ml) and sphingosine kinase inhibitor (SK1, 5 mu M), 90% of cells died. Neither LPS nor SKI alone at these doses damaged the cells. The LPS/SK1-nduced cell death was partially reversed by overexpression of HSP-70 in gene-transfected macrophages. The specificity of HSP-70 in this reversal was demonstrated by transfection of HSP-70-specific siRNA. Down-regulation of HSP-70 expression after transfection of siRNA specific for HSP-70 was associated with increased LPS/SK1-induced cell damage. Overexpression of INCB024360 human or murine HSP-70 (HSPA1A and Hspal a, respectively) increased both cellular SK1 mRNA and protein levels. Cellular heat shock also increased SK1

protein. These studies confirm the importance of SK1 as a protective moiety in LPS-incluced cell injury and demonstrate that HSP-70-mediated protection from cells treated with LPS/SK1 is accompanied by upregulating check details expression of SK1. HSP-70-mediated increases in SK1 and consequent increased levels of S1P may also play a role in protection of cells from other processes that lead to programmed cell death. Published by Elsevier Inc.”
“Recent evidence suggests that a genetic polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) mediates stress reactivity in adults. Little is known, however, about this gene-brain

association in childhood and adolescence, generally conceptualized as a time of heightened stress reactivity. The present study examines the association between 5-HTTLPR allelic variation and responses to fearful and angry faces presented both sub- and supraliminally in participants, ages 9-17. Behaviorally, carriers of the 5-HTTLPR short (s) allele exhibited significantly greater attentional bias to subliminally presented fear faces than did their long (l)-allele homozygous counterparts. Moreover, s-allele carriers showed greater neural activations to fearful and angry faces than did l-allele homozygotes in various regions of association cortex previously linked to attention control in adults.