a b s t r a c t XAP2 is member of a protein family sharing the TPR protein interaction motif. It displays close homology to the immunophilins FKBP51 and FKBP52 that act via the Hsp90 folding machinery to regulate the glucocorticoid receptor (GR). We show that XAP2 inhibits GR by reducing its responsiveness to hormone in transcriptional activation. The effect of XAP2 on GR requires its interaction with Hsp90 through the TPR motif. The PPIase-like region turned out to be enzymatically inactive. Thus, PPIase activity is not essential for the action of XAP2 on GR, similarly to FKBP51 and FKBP52.
Objectives: There is evidence that the antioxidant enzyme glyoxalase-1 (Glx-1) may play a role in anxiety-related behaviour. However, discordant findings between Glx-1 expression and anxiety-related behaviour have been observed in animal models. Because no data are available on the relation between Glx-1 mRNA expression and human anxiety so far, we investigated the expression of Glx-1 mRNA in peripheral red blood cells in relation to cholecystokinin-tetrapeptide (CCK-4) induced anxiety in healthy subjects. Methods: Twenty-three healthy subjects underwent challenge with CCK-4. Glx-1 mRNA expression was assessed by quantitative real-time polymerase chain reaction prior to CCK-4 injection. Baseline anxiety was assessed with the State-Trait-Anxiety-Inventory (STAI) and panic response was measured with the Panic Symptom Scale (PSS). Results: CCK-4 elicited a marked anxiety response accompanied by a significant increase in heart rate. Glx-1 mRNA expression correlated significantly with severity of CCK-4 induced anxiety. In contrast, Glx-1 activity did not correlate with state or trait anxiety. Conclusions: The positive correlation between Glx-1 mRNA expression and CCK-4 induced panic severity suggests that Glx-1 is involved into the acute anxiety response to CCK-4. Our preliminary findings support preclinical findings and point towards a role of Glx-1 for human anxiety.
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