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Proteasome inhibition with MG132 also increased the cytomegalovirus promoter-driven expression of Flag-HO-1 protein and resulted in an accumulation of ubiquitinated Flag-HO-1 in Flag-HO-1-overexpressing PC12 cells. In addition, a cycloheximide chase assay demonstrated that the degradation of Flag-HO-1 protein was slowed by MG-132. Next, the function of HO-1 which was upregulated by proteasome inhibitors was examined. Proteasome inhibitors protected dopaminergic neurons from 6-hydroxydopamine (6-OHDA)-induced toxicity and this neuroprotection was abrogated by co-treatment with zinc protoporphyrin IX, a HO-1 inhibitor. Furthermore, 6-OHDA-induced toxicity was blocked by bilirubin and carbon monoxide, [http://www.selleckchem.com/products/LBH-589.html learn more] products of the HO-1-catalyzed degradation of heme. These results suggest that mesencephalic HO-1 protein level is regulated by proteasome activity and the elevation by proteasome inhibition affords neuroprotection. ? 2010 Wiley-Liss, Inc. ""Heart failure (HF) patients show gray and white matter changes in multiple brain sites, including autonomic and motor coordination areas. It is [http://en.wikipedia.org/wiki/GUCY1B3 GUCY1B3] unclear whether the changes represent acute or chronic tissue pathology, a distinction necessary for understanding pathological processes that can be resolved with diffusion tensor imaging (DTI)-based mean diffusivity (MD) procedures. We collected four DTI series from 16 HF (age 55.1?��?7.8 years, 12 male) and 26 control (49.7?��?10.8 years, 17 male) subjects with a 3.0-Tesla magnetic resonance imaging scanner. MD maps were realigned, averaged, normalized, and smoothed. Global and regional MD values from autonomic and motor coordination sites were calculated by using normalized MD maps and brain masks; group MD values and whole-brain smoothed MD maps were compared by analysis of covariance (covariates; age and gender). Global brain MD (HF vs. controls, units �� 10?6 mm2/sec, 1103.8?��?76.6 vs. 1035.9?��?69.4, P?=?0.038) and regional autonomic and motor control site values (left insula, 1,085.4?�� 95.7 vs. 975.7?��?65.4, P?=?0.001; right insula, 1,050.2?�� 100.6 vs. 965.7?��?58.4, [http://www.selleckchem.com/products/Gefitinib.html Gefitinib] P?=?0.004; left hypothalamus, 1,419.6?��?165.2 vs. 1,234.9?��?136.3, P?=?0.002; right hypothalamus, 1,446.5?��?178.8 vs. 1,273.3?��?136.9, P?=?0.004; left cerebellar cortex, 889.1?��?81.9 vs. 796.6?��?46.8, P?