Seisuke Mimori

Publications (2)3.74 Total impact

• Source

  Available from: Masayuki Kaneko

  Article: Protective effects of 4-phenylbutyrate derivatives on the neuronal cell death and endoplasmic reticulum stress.

  Seisuke Mimori, Yasunobu Okuma, Masayuki Kaneko, Koichi Kawada, Toru Hosoi, Koichiro Ozawa, Yasuyuki Nomura, Hiroshi Hamana
  [show abstract] [hide abstract]
  ABSTRACT: Endoplasmic reticulum (ER) stress responses play an important role in neurodegenerative diseases. Sodium 4-phenylbutyrate (4-PBA) is a terminal aromatic substituted fatty acid that has been used for the treatment of urea cycle disorders. 4-PBA possesses in vitro chemical chaperone activity and reduces the accumulation of Parkin-associated endothelin receptor-like receptor (Pael-R), which is involved in autosomal recessive juvenile parkinsonism (AR-JP). In this study, we show that terminal aromatic substituted fatty acids, including 3-phenylpropionate (3-PPA), 4-PBA, 5-phenylvaleric acid, and 6-phenylhexanoic acid, prevented the aggregation of lactalbumin and bovine serum albumin. Aggregation inhibition increased relative to the number of carbons in the fatty acids. Moreover, these compounds protected cells against ER stress-induced neuronal cell death. The cytoprotective effect correlated with the in vitro chemical chaperone activity. Similarly, cell viability decreased on treatment with tunicamycin, an ER stress inducer, and was dependent on the number of carbons in the fatty acids. Moreover, the expression of glucose-regulated proteins 94 and 78 (GRP94, 78) decreased according to the number of carbons in the fatty acids. Furthermore, we investigated the effects of these compounds on the accumulation of Pael-R in neuroblastoma cells. 3-PPA and 4-PBA significantly suppressed neuronal cell death caused by ER stress induced by the overexpression of Pael-R. Overexpressed Pael-R accumulated in the ER of cells. With 3-PPA and 4-PBA treatment, the localization of the overexpressed Pael-R shifted away from the ER to the cytoplasmic membrane. These results suggest that terminal aromatic substituted fatty acids are potential candidates for the treatment of neurodegenerative diseases.
  Biological & Pharmaceutical Bulletin 01/2012; 35(1):84-90. · 1.66 Impact Factor
• Source

  Available from: Masayuki Kaneko

  Article: Expression of the ubiquitin ligase HRD1 in neural stem/progenitor cells of the adult mouse brain.

  Koichi Kawada, Masayuki Kaneko, Yasuyuki Nomura, Seisuke Mimori, Hiroshi Hamana, Kiyokazu Ogita, Toshihiko Murayama, Hiromichi Fujino, Yasunobu Okuma
  [show abstract] [hide abstract]
  ABSTRACT: Neural stem/progenitor cells (NSCs) reside in the subventricular zone (SVZ) and subgranular zone of the hippocampal dentate gyrus in adult mammals. The ubiquitin ligase HRD1 is associated with degradation of amyloid precursor protein and believed to be specifically expressed in neurons and not in astrocytes. We investigated expression of HRD1 using immunohistochemistry and found colocalization of HRD1 with the NSC marker protein nestin and glial fibrillary acidic protein in the NSCs of the SVZ (the SVZ astrocytes) but not in the hippocampus. In the hippocampal dentate gyrus, HRD1 is localized in the nucleus of nestin-positive cells.
  Journal of Pharmacological Sciences 01/2011; 117(3):208-12. · 2.08 Impact Factor