2 research outputs found
Lysine Addressability and Mammalian Cell Interactions of Bacteriophage λ Procapsids
Chemically or genetically modified
virus particles, termed viral
nanoparticles (VNPs), are being explored in applications such as drug
delivery, vaccine development, and materials science. Each virus platform
has inherent properties and advantages based on its structure, molecular
composition, and biomolecular interactions. Bacteriophage λ
was studied for its lysine addressability, stability, cellular uptake,
and the ability to modify its cellular uptake. λ procapsids
could be labeled primarily at a single residue on the gpE capsid protein
as determined by tandem mass spectrometry, providing a unique attachment
site for further capsid modification. Bioconjugation of transferrin
to the procapsids mediated specific interaction with transferrin receptor-expressing
cells. These studies demonstrate the utility of bacteriophage λ
procapsids and their potential use as targeted drug delivery vehicles
Cuprizone Intoxication Induces Cell Intrinsic Alterations in Oligodendrocyte Metabolism Independent of Copper Chelation
Cuprizone
intoxication is a common animal model used to test myelin
regenerative therapies for the treatment of diseases such as multiple
sclerosis. Mice fed this copper chelator develop reversible, region-specific
oligodendrocyte loss and demyelination. While the cellular changes
influencing the demyelinating process have been explored in this model,
there is no consensus about the biochemical mechanisms of toxicity
in oligodendrocytes and about whether this damage arises from the
chelation of copper <i>in vivo</i>. Here we have identified
an oligodendroglial cell line that displays sensitivity to cuprizone
toxicity and performed global metabolomic profiling to determine biochemical
pathways altered by this treatment. We link these changes with alterations
in brain metabolism in mice fed cuprizone for 2 and 6 weeks. We find
that cuprizone induces widespread changes in one-carbon and amino
acid metabolism as well as alterations in small molecules that are
important for energy generation. We used mass spectrometry to examine
chemical interactions that are important for copper chelation and
toxicity. Our results indicate that cuprizone induces global perturbations
in cellular metabolism that may be independent of its copper chelating
ability and potentially related to its interactions with pyridoxal
5′-phosphate, a coenzyme essential for amino acid metabolism