Midkine as a factor to counteract the deposition of amyloid β-peptide plaques: in vitro analysis and examination in knockout mice

<p>Abstract</p> <p>Background</p> <p>Midkine is a heparin-binding cytokine involved in cell survival and various inflammatory processes. Midkine accumulates in senile plaques of patients with Alzheimer's disease, while it counteracts the cytotoxic effects of amyloid β-peptide and inhibits its oligomerization. The present study was conducted to understand the role of midkine upon plaque formation of amyloid β-peptide.</p> <p>Methods</p> <p>A surface plasmon assay was performed to determine the affinity of midkine for amyloid β-peptide. The deposition of amyloid β-peptide was compared in the brain of wild-type and midkine-deficient mice. An effect of midkine to microglias was examined by cell migration assay.</p> <p>Results</p> <p>Midkine bound to amyloid β-peptide with the affinity of 160 nM. The C-terminal half bound to the peptide more strongly than the N-terminal half, and heparin inhibited midkine from binding to the peptide. Pleiotrophin, which has about 50% sequence identity with midkine also bound to amyloid β-peptide. The deposition of amyloid β-peptide plaques in the cortex and hippocampus was more intense in 15-month-old midkine-deficient mice, compared to the corresponding wild-type mice. Midkine promoted migration of microglias in culture.</p> <p>Conclusions</p> <p>These results are consistent with the view that midkine attenuates the deposition of amyloid β-peptide plaques, and thus progression of Alzheimer's disease, by direct binding and also by promoting migration of microglias.</p

Three-dimensional structure of monoanionic methionine-enkephalin: X-ray structure of tert-butyloxycarbonyl-Tyr-Gly-Gly-(4-bromo)Phe-Met-OH

AbstractThe conformation of tert-butyloxycarbonyl-Tyr-Gly-Gly-(4-bromo)Phe-Met-OH, as a monoanionic derivative of Met-enkephalin, was elucidated by X-ray crystal analysis. The molecule took an extended conformation which was bended at the Phe residue. The implication of the dimer formation caused by 4 intermolecular hydrogen bonds was discussed in the relation with the opiate receptor

Topological isomers of human uroguanylin: interconversion between biologically active and inactive isomers

AbstractThe solution structures of the two compounds of human uroguanylin (I and II), which were generated during disulfide bond forming reaction, were found to be topological isomers by 1H-nuclear magnetic resonance spectroscopy. These isomers are interconvertible in aqueous media at rates which vary with the pH and temperature of the solution. Because compound I is active in the cGMP producing assay, but compound II is not, this interconversion may be useful for evaluating the activity of human uroguanylin both in vivo and in vitro

Quantum critical behavior of the hyperkagome magnet Mn3CoSi

β-Mn-type family alloys Mn3TX (T = Co, Rh, and Ir; X = Si and Ge) have a three-dimensional antiferromagnetic (AF) corner-shared triangular network, i.e., the hyperkagome lattice. The antiferromagnet Mn3RhSi shows magnetic short-range order over a wide temperature range of approximately 500 K above the Néel temperature TN of 190 K. In this family of compounds, as the lattice parameter decreases, the long-range magnetic ordering temperature decreases. Mn3CoSi has the smallest lattice parameter and the lowest TN in the family. The quantum critical point (QCP) from AF to the quantum paramagnetic state is expected near a cubic lattice parameter of 6.15 Å. Although the Néel temperature of Mn3CoSi is only 140 K, the emergence of the quantum critical behavior in Mn3CoSi is discussed. We study how the magnetic short-range order appears in Mn3CoSi by using neutron scattering, μSR, and bulk characterization such as specific heat capacity. According to the results, the neutron scattering intensity of the magnetic short-range order in Mn3CoSi does not change much at low temperatures from that of Mn3RhSi, although the μSR short-range order temperature of Mn3CoSi is largely suppressed to 240 K from that of Mn3RhSi. Correspondingly, the volume fraction of the magnetic short-range order regions, as shown by the initial asymmetry drop ratio of μSR above TN, also becomes small. Instead, the electronic-specific heat coefficient γ of Mn3CoSi is the largest in this Mn3T Si system, possibly due to the low-energy spin fluctuation near the quantum critical point