Ziram and sodium N,N-dimethyldithiocarbamate inhibit ubiquitin activation through intracellular metal transport and increased oxidative stress in HEK293 cells.

Ubiquitin activating enzyme E1 plays a pivotal role in ubiquitin based protein signaling through regulating the initiating step of the cascade. Previous studies demonstrated that E1 is inhibited by covalent modification of reactive cysteines contained within the ubiquitin-binding groove and by conditions that increase oxidative stress and deplete cellular antioxidants. In this study, we determined the relative contribution of covalent adduction and oxidative stress to E1 inhibition produced by ziram and sodium N,N-dimethyldithiocarbamate (DMDC) in HEK293 cells.

Augmented cardiac formation of oxidatively-induced carbonylated proteins accompanies the increased functional severity of post-myocardial infarction heart failure in the setting of type 1 diabetes mellitus.

Summary: Heart failure (HF) is a dominant cause for the higher mortality of diabetics after myocardial infarction (MI). In the present investigation, we have discovered that higher levels of oxidative stress (OS)-induced carbonylated proteins accompany worsening post-MI HF in the presence of type 1 diabetes. These findings provide a mechanistic link between amplified OS and exacerbation of post-infarction HF in diabetes.

NADPH oxidases and reactive oxygen species at different stages of chronic hypoxia-induced pulmonary hypertension in newborn piglets.

Recently, we reported that reactive oxygen species (ROS) generated by NADPH oxidase (NOX) contribute to aberrant responses in pulmonary resistance arteries (PRAs) of piglets exposed to 3 days of hypoxia (Am J Physiol Lung Cell Mol Physiol 295: L881-L888, 2008). An objective of the present study was to determine whether NOX-derived ROS also contribute to altered PRA responses at a more advanced stage of pulmonary hypertension, after 10 days of hypoxia. We further wished to advance knowledge about the specific NOX and antioxidant enzymes that are altered at early and later stages of pulmonary hypertension.

Regional expression of brain derived neurotrophic factor (BDNF) is correlated with dynamic patterns of promoter methylation in the developing mouse forebrain.

Brain Derived Neurotrophic Factor (BDNF) plays an important role in brain development and plasticity. BDNF gene expression is known to be dynamically regulated during development, but the regulatory controls of normal differential expression are not well understood. Methylation of CpG dinucleotides within gene promoters is emerging as an important epigenetic control mechanism of transcription, and the BDNF complex promoter contains several CpG dinucleotides.