The branched-chain aminotransferase proteins: Novel redox chaperones for protein disulfide isomerase-implications in Alzheimer's disease

Aims: The human branched-chain aminotransferase proteins (hBCATm and hBCATc) are regulated through oxidation and S-nitrosation. However, it remains unknown whether they share common redox characteristics to enzymes such as protein disulfide isomerase (PDI) in terms of regulating cellular repair and protein misfolding. Results: Here, similar to PDI, the hBCAT proteins showed dithiol-disulfide isomerase activity that was mediated through an S-glutathionylated mechanism. Site-directed mutagenesis of the active thiols of the CXXC motif demonstrates that they are fundamental to optimal protein folding. Far Western analysis indicated that both hBCAT proteins can associate with PDI. Co-immunoprecipitation studies demonstrated that hBCATm directly binds to PDI in IMR-32 cells and the human brain. Electron and confocal microscopy validated the expression of PDI in mitochondria (using Mia40 as a mitochondrial control), where both PDI and Mia40 were found to be co-localized with hBCATm. Under conditions of oxidative stress, this interaction is decreased, suggesting that the proposed chaperone role for hBCATm may be perturbed. Moreover, immunohistochemistry studies show that PDI and hBCAT are expressed in the same neuronal and endothelial cells of the vasculature of the human brain, supporting a physiological role for this binding. Innovation: This study identifies a novel redox role for hBCAT and confirms that hBCATm differentially binds to PDI under cellular stress. Conclusion: These studies indicate that hBCAT may play a role in the stress response of the cell as a novel redox chaperone, which, if compromised, may result in protein misfolding, creating aggregates as a key feature in neurodegenerative conditions such as Alzheimer's disease. © 2014 Mary Ann Liebert, Inc

Challenging the survival thresholds of a desert cyanobacterium under laboratory simulated and space conditions

Knowledge of the limit of life’s adaptability to extreme environments is essential for identifying potentially habitable niches in planets and moons in our Solar System or in planetary systems around other stars. Dryness is one of the main life-threatening factors since water removal causes membrane phase transition and production of reactive oxygen species that cause lipid peroxidation, protein oxidation and DNA damage, which are lethal to most organisms. Anhydrobiotic cyanobacteria of the genus Chroococcidiopsis possess a remarkable resistance to desiccation and radiation; as such they have extended the limits of life as we know it in several new directions. Investigating the threshold of such resistance can help us in understanding not only the limits of life on Earth but also in assessing the potential habitability of Mars, of icy moons, and of exoplanets characterized by high doses of radiation and transient availability of liquid water. New insights have been provided by experiments exposing cyanobacteria to laboratory simulations that mimic planetary conditions, and also to real space conditions