Biology subjects

Arai, M.

Publications and source records attributed to Arai, M..

21 records · Page 2Linked to original sources

bioRxiv2020

Angiopathy with impaired glucose logistics observed in schizophrenia-like model mice

Metabolic dysfunction is thought to contribute to the severity of psychiatric disorders; however, it has been unclear whether current high-simple-sugar diets contribute to pathogenesis of these diseases. Here we demonstrate that a high-sucrose diet during adolescence induces psychosis-related behavioral endophenotypes, including hyperactivity, poor working memory, impaired sensory gating, and disrupted interneuron function in mice deficient for glyoxalase-1 (Glo1), an enzyme involved in detoxification of sucrose metabolites. Further, the high-sucrose diet induced microcapillary impairments and reduced brain glucose uptake in brains of Glo1 deficient mice. Aspirin protected against this angiopathy, enhancing brain glucose uptake, and preventing abnormal behavioral phenotypes. Similar vascular damage to our model mice was found in the brains of randomly collected schizophrenia and bipolar disorder patients, suggesting that psychiatric disorders are associated with angiopathy in the brain caused by various environmental stresses, including metabolic stress.

neuroscience↗

bioRxiv2019

GUN1 regulates tetrapyrrole biosynthesis

The biogenesis of the photosynthetic apparatus in developing chloroplasts requires the assembly of proteins encoded on both nuclear and chloroplast genomes1. To co-ordinate this process there needs to be communication between these organelles, and while we have a good understanding of how the nucleus controls chloroplast development, how the chloroplast communicates with the nucleus at this time is still essentially unknown2. What we do know comes from pioneering work in which a series of genomes uncoupled (gun) mutants were identified that show elevated nuclear gene expression after chloroplast damage3. Of the six reported gun mutations, five are in tetrapyrrole biosynthesis proteins4-6 and this has led to the development of a model for chloroplast-to-nucleus retrograde signaling in which ferrochelatase 1 (FC1)-dependent heme synthesis generates a positive signal promoting expression of photosynthesis-related genes6. However, the molecular consequences of the strongest of the gun mutants, gun17, is unknown, preventing the development of a unifying hypothesis for chloroplast-to-nucleus signaling. Here, we show that GUN1 directly binds to heme and other metal-porphyrins, affects flux through the tetrapyrrole biosynthesis pathway and can increase the chelatase activity of FC1. These results raise the possibility that the signaling role of GUN1 may be manifested through changes in tetrapyrrole metabolism and supports a role for tetrapyrroles as mediators of a single biogenic chloroplast-to-nucleus retrograde signaling pathway.

plant biology↗

bioRxiv2017

Spatial and temporal translocation of PKCα in single endothelial cell in response to focal mechanical stimulus

We observed the kinetics of protein kinase C (PKC) and the intracellular Ca2+ wave in endothelial cells (ECs) in response to microscopic mechanical stress to investigate the effect of mechanical stress on PKC translocation. The results show that a focal mechanical stimulus induced biphasic and directional PKC translocation; PKC initially translocated toward distinct spots near or at the membrane and then accumulated at the stimulus point. The low initial translocation occurred simultaneously in parallel with the increase in Ca2+. Initial translocation was inhibited in spite of Ca2+ increase when the diacylglycerol (DAG) binding domain of PKC was inhibited, suggesting that translocation requires intracellular Ca2+ increase and DAG. On the other hand, high secondary translocation was delayed, occurring after the Ca2+ wave; however, this secondary translocation occurred even when Ca2+ release from the endoplasmic reticulum was inhibited, while it did not occur when the mechanosensitive (MS) channel was inhibited. These results indicated that at least Ca2+ influx through MS channels is required. Our results support the implication of PKC in the Ca2+ signaling pathway in response to mechanical stress in ECs.\n\nSummary statementIn response to a focal mechanical stimulus, PKC in an endothelial cell was initially translocated toward distinct spots near or at the membrane and then accumulated at the stimulus point.

cell biology↗