122 research outputs found
Interactions between Anticancertrans-Platinum Compounds and Proteins: Crystal Structures and ESI-MS Spectra of Two Protein Adducts of trans-(Dimethylamino)(methylamino)dichloridoplatinum(II)
The adducts formed between trans-
(dimethylamino)(methylamino)dichloridoplatinum(II),
[t-PtCl2(dma)(ma)], and two model proteins, i.e., hen egg
white lysozyme and bovine pancreatic ribonuclease, were
independently characterized by X-ray crystallography and
electrospray ionization mass spectrometry. In these
adducts, the PtII center, upon chloride release, coordinates
either to histidine or aspartic acid residues while both
alkylamino ligands remain bound to the metal. Comparison
with the cisplatin derivatives of the same proteins
highlights for [t-PtCl2(dma)(ma)] a kind of biomolecular
metalation remarkably different from that of cisplatin
Safety and efficacy evaluation in vivo of a cationic nucleolipid nanosystem for the nanodelivery of a ruthenium(III) complex with superior anticancer bioactivity
Les Houches 2015: Physics at TeV Colliders Standard Model Working Group Report
This Report summarizes the proceedings of the 2015 Les Houches workshop on
Physics at TeV Colliders. Session 1 dealt with (I) new developments relevant
for high precision Standard Model calculations, (II) the new PDF4LHC parton
distributions, (III) issues in the theoretical description of the production of
Standard Model Higgs bosons and how to relate experimental measurements, (IV) a
host of phenomenological studies essential for comparing LHC data from Run I
with theoretical predictions and projections for future measurements in Run II,
and (V) new developments in Monte Carlo event generators.Comment: Proceedings of the Standard Model Working Group of the 2015 Les
Houches Workshop, Physics at TeV Colliders, Les Houches 1-19 June 2015. 227
page
Mitochondrial Uncoupling Protein-2 (UCP2) Mediates Leptin Protection Against MPP+ Toxicity in Neuronal Cells
Mitochondrial dysfunction is involved in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). Uncoupling proteins (UCPs) delink ATP production from biofuel oxidation in mitochondria to reduce oxidative stress. UCP2 is expressed in brain, and has neuroprotective effects under various toxic insults. We observed induction of UCP2 expression by leptin in neuronal cultures, and hypothesize that leptin may preserve neuronal survival via UCP2. We showed that leptin preserved cell survival in neuronal SH-SY5Y cells against MPP+ toxicity (widely used in experimental Parkinsonian models) by maintaining ATP levels and mitochondrial membrane potential (MMP); these effects were accompanied by increased UCP2 expression. Leptin had no effect in modulating reactive oxygen species levels. Stable knockdown of UCP2 expression reduced ATP levels, and abolished leptin protection against MPP+-induced mitochondrial depolarization, ATP deficiency, and cell death, indicating that UCP2 is critical in mediating these neuroprotective effects of leptin against MPP+ toxicity. Interestingly, UCP2 knockdown increased UCP4 expression, but not of UCP5. Our findings show that leptin preserves cell survival by maintaining MMP and ATP levels mediated through UCP2 in MPP+-induced toxicity
Mutations in disordered regions can cause disease by creating dileucine motifs
Many disease-causing missense mutations affect intrinsically disordered regions (IDRs) of proteins, but the molecular mechanism of their pathogenicity is enigmatic. Here, we employ a peptide-based proteomic screen to investigate the impact of mutations in IDRs on protein-protein interactions. We find that mutations in disordered cytosolic regions of three transmembrane proteins (GLUT1, ITPR1, and CACNA1H) lead to an increased clathrin binding. All three mutations create dileucine motifs known to mediate clathrin-dependent trafficking. Follow-up experiments on GLUT1 (SLC2A1), the glucose transporter causative of GLUT1 deficiency syndrome, revealed that the mutated protein mislocalizes to intracellular compartments. Mutant GLUT1 interacts with adaptor proteins (APs) in vitro, and knocking down AP-2 reverts the cellular mislocalization and restores glucose transport. A systematic analysis of other known disease-causing variants revealed a significant and specific overrepresentation of gained dileucine motifs in structurally disordered cytosolic domains of transmembrane proteins. Thus, several mutations in disordered regions appear to cause "dileucineopathies.
Improvements in the order, isotropy and electron density of glypican-1 crystals by controlled dehydration
Theoretical Estimation of Vibrational Frequencies Involving Transition Metal Compounds
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
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