Myeloperoxidase (MPO) Gene Polymorphisms are not Associated with Japanese Patients with COPD

Article信州医学雑誌 68(1): 41-48(2020)journal articl

Impaired degradation followed by enhanced recycling of epidermal growth factor receptor caused by hypo-phosphorylation of tyrosine 1045 in RBE cells

信州大学博士（医学）・学位論文・平成24年6月11日授与（甲第929号）・桂安萍Background: Since cholangiocarcinoma has a poor prognosis, several epidermal growth factor receptor (EGFR)-targeted therapies with antibody or small molecule inhibitor treatment have been proposed. However, their effect remains limited. The present study sought to understand the molecular genetic characteristics of cholangiocarcinoma related to EGFR, with emphasis on its degradation and recycling. Methods: We evaluated EGFR expression and colocalization by immunoblotting and immunofluorescence, cell surface EGFR expression by fluorescence-activated cell sorting (FACS), and EGFR ubiquitination and protein binding by immunoprecipitation in the human cholangiocarcinoma RBE and immortalized cholangiocyte MMNK-1 cell lines. Monensin treatment and Rab11a depletion by siRNA were adopted for inhibition of EGFR recycling. Results: Upon stimulation with EGF, ligand-induced EGFR degradation was impaired and the expression of phospho-tyrosine 1068 and phospho-p44/42 MAPK was sustained in RBE cells as compared with MMNK-1 cells. In RBE cells, the process of EGFR sorting for lysosomal degradation was blocked at the early endosome stage, and non-degradated EGFR was recycled to the cell surface. A disrupted association between EGFR and the E3 ubiquitin ligase c-Cbl, as well as hypo-phosphorylation of EGFR at tyrosine 1045 (Tyr1045), were also observed in RBE cells. Conclusion: In RBE cells, up-regulation of EGFR Tyr1045 phosphorylation is a potentially useful molecular alteration in EGFR-targeted therapy. The combination of molecular-targeted therapy determined by the characteristics of individual EGFR phosphorylation events and EGFR recycling inhibition show promise in future treatments of cholangiocarcinoma.ArticleBMC Cancer. 2012, 12:179journal articl

Structural characterization of N-lignoceroyl (C24:0) sphingomyelin bilayer membranes : A reevaluation

Sphingomyelin (SM) is a membrane lipid and plays important roles in signaling, protein trafficking, cell growth and death. We investigated the structure of hydrated highly asymmetric SM, N-Lignoceroyl (C24:0) SM, bilayers with X-ray diffraction (XRD), simultanous small angle X-ray scattering (SAXS) and wide angle XRD, and SAXS measurements. At temperatures between two endothermic transitions of hydrated C24:0 SM bilayers, the C24:0 SM formed a ripple phase with the ripple periodicity of ~12-14 nm. About 3 month incubation at 277 K induced the formation of a stable phase with a short lamellar spacing of 5.62 nm. Based upon the structures revealed by this study and the phase behavior, we discuss the intermolecular interactions between C24:0 SM molecules in the bilayer membrane

Mechanisms of Neuronal Death in Synucleinopathy

α-synuclein is a key molecule in the pathogenesis of synucleinopathy including Parkinson's disease and multiple system atrophy. In this mini-review, we mainly focus on recent data obtained from cellular models of synucleinopathy and discuss the possible mechanisms of neurodegeneration. Recent progress suggests that the aggregate formation of α-synuclein is cytoprotective and that its precursor oligomer (protofibril) may be cytotoxic. The catechol-derived quinones are the candidate molecules that facilitate the oligomer formation of α-synuclein. Furthermore, the cellular membranes are shown to be the primary targets injured by mutant α-synucleins, and the mitochondrial dysfunction seems to be an initial step in the neuronal death