27 research outputs found
MDGA1, an IgSF molecule containing a MAM domain, heterophilically associates with axon- and muscle-associated binding partners through distinct structural domains.
No full textMolecules belonging to the immunoglobulin superfamily (IgSF) are reported to be involved in intercellular communication in the developing nervous system. We have identified a novel GPI-anchored IgSF molecule containing a MAM (meprin, A5 protein, PTPμ) domain, named MDGA1, by screening for genes that are expressed by subpopulations of cells in the embryonic chick spinal cord. MDGA1 is selectively expressed by brachial LMCm motor neurons, some populations of DRG neurons, and interneurons. We found that MDGA1 interacts heterophilically with axon-rich regions, mainly through its MAM domain. Interestingly, MDGA1 also interacts with differentiating muscle through its N-terminal region, which contains Ig domains. These results suggest that MDGA1 functions in MDGA1-expressing nerves en route to and at their target site
Early Decrease of XRCC1, a DNA Base Excision Repair Protein, May Contribute to DNA Fragmentation After Transient Focal Cerebral Ischemia in Mice
No full text
Background and Purpose
—DNA damage and the DNA repair mechanism are known to be involved in ischemia/reperfusion injury in the brain. The x-ray repair cross-complementing group 1 (XRCC1) protein plays a central role in the DNA base excision repair pathway by interacting with DNA ligase III and DNA polymerase β. The present study examined the protein expression of XRCC1 and DNA fragmentation before and after transient focal cerebral ischemia (FCI).
Methods
—Adult male CD-1 mice were subjected to 60 minutes of FCI by intraluminal blockade of the middle cerebral artery. XRCC1 protein expression was analyzed by immunohistochemistry and Western blot analysis. DNA damage was evaluated by gel electrophoresis and terminal deoxynucleotidyl transferase–mediated uridine 5′-triphosphate-biotin nick end-labeling (TUNEL). The spatial relationship between XRCC1 expression and DNA damage was examined by double staining with XRCC1 and TUNEL after FCI.
Results
—Immunohistochemistry showed the nuclear expression of XRCC1 in all regions of the control brains and that it was predominant in the hippocampus. The XRCC1 level was markedly reduced in the caudate putamen at 10 minutes, further decreased in the entire middle cerebral artery territory at 1 hour, and remained reduced until 4 and 24 hours after FCI. Western blot analysis of the normal control brain showed a characteristic band of 70 kDa, which decreased after FCI. A significant amount of DNA fragmentation was detected by DNA gel electrophoresis 24 hours but not 4 hours after FCI. Double staining showed that the neurons that lost XRCC1 immunoreactivity became TUNEL positive.
Conclusions
—These results suggest that the early decrease of XRCC1 and the failure of the DNA repair mechanism may contribute, at least in part, to DNA fragmentation after FCI.
</jats:p
Heterogeneity of mouse primordial germ cells reflecting the distinct status of their differentiation, proliferation and apoptosis can be classified by the expression of cell surface proteins integrin α6 and c-Kit
No full textReduction of Apurinic/Apyrimidinic Endonuclease Expression After Transient Global Cerebral Ischemia in Rats
No full text
Background and Purpose
—To clarify the relationship between apurinic/apyrimidinic endonuclease (APE/Ref-1), a multifunctional protein in the DNA base excision repair pathway, and delayed neuronal cell death associated with apoptosis, we examined the expression of APE/Ref-1 before and after transient global ischemia in rats.
Methods
—Global ischemia was induced by bilateral common carotid artery occlusion and hypotension. Expression of the APE/Ref-1 protein was evaluated by Western blot and immunohistochemical analyses. Apoptosis after global ischemia was observed by DNA electrophoresis and terminal deoxynucleotidyl transferase–mediated uridine 5′-triphosphate-biotin nick end labeling (TUNEL) staining.
Results
—Immunohistochemistry showed the nuclear expression of APE/Ref-1 in the control brains. Nuclear immunoreactivity of APE/Ref-1 was significantly decreased 2 days after 10 minutes of ischemia in the hippocampal CA1 subregion. Western blot analysis of a sample from the normal brains showed a characteristic 37-kDa band, which was reduced in the hippocampal CA1 subregion after ischemia. A significant amount of DNA fragmentation was observed at 3 days but not at 1 day after ischemia. Double staining with APE/Ref-1 and TUNEL clearly showed that the neurons that lost APE/Ref-1 immunoreactivity became TUNEL positive.
Conclusions
—Our data provide evidence that APE/Ref-1 decreased in hippocampal CA1 neurons after transient global ischemia and that this reduction precedes DNA fragmentation, which is destined to cause apoptosis. Our results suggest the possibility that a decrease of APE/Ref-1 activity and the failure of DNA repair may underlie the mechanism of apoptosis after transient focal ischemia.
</jats:p
Heterogeneity of social cognition between visual perspective-taking and theory of mind in the temporo-parietal junction
No full textVisual perspective taking (VPT), particularly level 2 VPT (VPT2), which allows an individual to understand that the same object can be seen differently by others, is related to the theory of mind (ToM), because both functions require a decoupled representation from oneself. Although previous neuroimaging studies have shown that VPT2 and ToM activate the temporo-parietal junction (TPJ), it is unclear whether common neural substrates are involved in both functions. To clarify this point, we directly compared the TPJ activation patterns of individual participants performing VPT2 and ToM tasks using functional magnetic resonance imaging and within-subjects design. A whole-brain analysis revealed that VPT2 and ToM activated overlapping areas in the posterior part of the TPJ. In addition, we found that both the peak coordinates and activated regions for ToM were located significantly more anteriorly and dorsally within the bilateral TPJ than those measured during the VPT2 task. We further confirmed that these activated areas were spatially distinct from the nearby extrastriate body area (EBA), visual motion area (MT+), and the posterior superior temporal sulcus (pSTS) using independent localizer scans. Our findings revealed that VPT2 and ToM have gradient representations, indicating the functional heterogeneity of social cognition within the TPJ
MDGA1, an IgSF molecule containing a MAM domain, heterophilically associates with axon- and muscle-associated binding partners through distinct structural domains.
No full textAbstract LB-207: ΔNp63α regulates quiescence, stem or progenitor activity of normal and malignant breast cells in a cell type-specific manner
No full textAssociation between 4-year all-cause mortality and carnitine profile in maintenance hemodialysis patients
No full text東京女子医科大学博士(医学)博士(医学) 乙第3045号(主論文の要旨、要約、審査結果の要旨、本文)，著者名:Yuiko KAMEI・Daigo KAMEI・Ken TSUCHIYA・Michio MINESHIMA・Kosaku NITTA，タイトル:Association between 4-year all-cause mortality and carnitine profile in maintenance hemodialysis patients，掲載誌:PloS one(1932-6203)，巻・頁・年:13巻8号 p.e0201591(2018)，著作権関連情報:© 2018 Kamei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.，DOI:10.1371/journal.pone.0201591doctoral thesi
Association between 4-year all-cause mortality and carnitine profile in maintenance hemodialysis patients
No full text博士(医学) 乙第3045号(主論文の要旨、要約、審査結果の要旨、本文)，著者名:Yuiko KAMEI・Daigo KAMEI・Ken TSUCHIYA・Michio MINESHIMA・Kosaku NITTA，タイトル:Association between 4-year all-cause mortality and carnitine profile in maintenance hemodialysis patients，掲載誌:PloS one(1932-6203)，巻・頁・年:13巻8号 p.e0201591(2018)，著作権関連情報:© 2018 Kamei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.，DOI:10.1371/journal.pone.020159
The Cytosolic Antioxidant Copper/Zinc-Superoxide Dismutase Prevents the Early Release of Mitochondrial Cytochrome c in Ischemic Brain after Transient Focal Cerebral Ischemia in Mice
No full textRelease of mitochondrial cytochrome c into the cytosol is a critical step in apoptosis. We have reported that early release of cytochrome cin vivooccurs after permanent focal cerebral ischemia (FCI) and is mediated by the mitochondrial antioxidant manganese superoxide dismutase (SOD). However, the role of reactive oxygen species produced after ischemia–reperfusion in the mitochondrial apoptosis process is still unknown, although overexpression of copper/zinc-SOD (SOD1), a cytosolic isoenzyme, protects against ischemia–reperfusion. We now hypothesize that the overexpression of SOD1 also prevents apoptosis after FCI. To address this issue, we examined the subcellular distribution of the cytochrome c protein in both wild-type mice and in SOD1 transgenic (Tg) mice after transient FCI. Cytosolic cytochrome c was detected as early as 2 hr after reperfusion, and correspondingly, mitochondrial cytochrome c was significantly reduced after FCI. Cytosolic cytochrome c was significantly lower in the SOD1 Tg mice compared with wild types 2 (p< 0.0001) and 4 (p< 0.05) hr after FCI. Apaf-1, which interacts with cytochrome c and activates caspases, was constitutively expressed in both groups of animals, with no alteration after FCI. Double staining with cytochrome c immunohistochemistry and terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling showed a spatial relationship between cytosolic cytochrome c expression and DNA fragmentation. A significant amount of DNA laddering was detected 24 hr after ischemia and was reduced in SOD1 Tg mice. These data suggest that SOD1 blocks cytosolic release of cytochrome c and could thereby reduce apoptosis after transient FCI.</jats:p
