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Masato Matsuoka

Publications and source records attributed to Masato Matsuoka.

At least 19 recordsLinked to original sources
PubMed2005

High levels of pigment epithelium-derived factor in the retina of a rat model of type 2 diabetes.

Spontaneously diabetic Torii (SDT) rats are a new animal model of diabetes. To investigate the mechanisms controlling diabetic retinopathy, we examined the retinal changes in SDT rats and determined the molecular balance between pigment epithelium-derived factor (PEDF), an angiogenic inhibitor, and vascular endothelial growth factor (VEGF), a major angiogenic stimulator. The retinopathy in SDT rats was characterized by a low incidence of neovascular formation and absence of non-perfused areas, and high levels of both PEDF and VEGF. Proliferative neovascular membranes, that are similar to that in human eyes with proliferative diabetic retinopathy, were found in the eyes of some of the SDT rats at >50-weeks-of-age, Immunoreactivity for VEGF was detected in the retina of SDT rats and the level of VEGF increased with the duration of diabetes. More importantly, immunoreactivity for PEDF was also increased in the retina of diabetic SDT rats. Western blot analysis showed that the level of VEGF in the retina was increased by 2.4 fold at 20-week-old, and by 6.8 fold at >40-week-old compared to that of 10-weeks old SDT rats. The levels of PEDF in the retina at 20-week- and at >40-week-old were significantly higher than that of 10-weeks old SDT rats (20-week-old; 13.5-fold increase, > 40-week-old; 10.3-fold increase). Earlier studies showed that the level of PEDF was decreased and VEGF was increased in proliferative diabetic retinopathy in human eyes. The high levels of PEDF in the retina of SDT rats may contribute to the low incidence of neovascular formation and absence of non-perfused areas that do not match the typical diabetic retinopathy in humans.

Animals↗
PubMed2004

Increased levels of platelet-derived microparticles in patients with diabetic retinopathy.

Diabetic retinopathy is caused by capillary occlusions. Platelet-derived microparticles (PMPs) stimulate the coagulation cascade and increase leukocyte and endothelial cell adhesions, both of which are key events in the development of diabetic retinopathy. However, the correlation between the levels of PMPs and diabetic retinopathy has not been precisely determined. The PMPs levels and the expression of platelet CD62P and CD63 were measured in 92 diabetic patients. The level of PMPs was significantly correlated with the expression of CD62P (r = 0.76, P < 0.0001) and CD63 (r = 0.71, P < 0.0001). The mean level of PMPs in diabetics (507+/-15/10(4) platelets (plt), mean+/-S.E.) was significantly higher than that in normal. The PMPs levels increased with the progression of the diabetic retinopathy; 480+/-28/10(4) plt in diabetic patients without retinopathy (n = 25), 504+/-40/10(4) plt with mild or moderate non-proliferative diabetic retinopathy (n = 13), 512+/-29/10(4) plt with severe non-proliferative diabetic retinopathy (n = 25), and 528+/-25/10(4) plt with proliferative diabetic retinopathy (n=29). The PMPs level in patients with non-perfused retinal areas (582+/-27/10(4) plt, n = 24) was significantly higher than patients without non-perfused areas (469+/-23/10(4) plt, n = 30; P = 0.0096) and without diabetic retinopathy (P = 0.024). These high correlations indicate that increased levels of PMPs may accelerate diabetic retinopathy.

Adult↗
PubMed2004

Requirement of MKK4 and MKK7 for CdCl2- or HgCl2-induced activation of c-Jun NH2-terminal kinase in mouse embryonic stem cells.

c-Jun NH(2)-terminal kinase (JNK), also known as stress-activated protein kinase (SAPK), is activated primarily by inflammatory cytokines and environmental stresses including toxic metal exposure. To reveal the upstream kinase responsible for JNK activation by toxic metals, the phosphorylation status and the activity of JNK were examined in mouse embryonic stem (ES) cells lacking MKK4 or MKK7 following exposure to CdCl(2) or HgCl(2). Treatment with CdCl(2) or HgCl(2) induced the phosphorylation of JNK in a dose- and time-dependent manner in wild-type ES cells. In both mkk4(-/-) and mkk7(-/-) ES cells, CdCl(2)- or HgCl(2)-induced phosphorylation and activation of JNK were suppressed significantly. However, in mkk7(-/-) ES cells treated with CdCl(2) and HgCl(2), JNK activation was not abolished (suppressed by 56% and 78%, respectively). These findings suggest that the full activation of JNK by toxic metal exposure requires both MKK4 and MKK7, and these upstream kinases might contribute differentially in JNK activation between mouse ES cells exposed to CdCl(2) and HgCl(2).

Animals↗
PubMed2004

Suppression of cadmium-induced JNK/p38 activation and HSP70 family gene expression by LL-Z1640-2 in NIH3T3 cells.

When NIH3T3 cells were exposed to CdCl(2), the three major mitogen-activated protein kinases (MAPKs), extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38, were phosphorylated in a time (1-9 h)- and dose (1-20 microM)-dependent manner. Treatment with a macrocyclic nonaketide compound, LL-Z1640-2 (10-100 ng/ml), suppressed the phosphorylation of MAPKs without affecting the total protein level in cells exposed to 10 microM CdCl(2) for 6 h. CdCl(2)-induced phosphorylation of c-Jun on Ser63 and that on Ser73, and resultant accumulation of total c-Jun protein were also suppressed by LL-Z1640-2 treatment. The in vitro kinase assays also showed significant inhibitory effects of LL-Z1640-2 (at 10 or 25 ng/ml) on JNK and p38 but less markedly. In contrast to JNK and p38, ERK activity was inhibited moderately only at 50 or 100 ng/ml LL-Z1640-2. On the other hand, other JNK inhibitors, SP600125 and L-JNKI1, failed to suppress CdCl(2)-induced activation of the JNK pathway. Among the mouse stress response genes upregulated in response to CdCl(2) exposure, the expressions of hsp68 (encoding for heat shock 70 kDa protein 1; Hsp70-1) and grp78 (encoding for 78 kDa glucose-regulated protein; Grp78) genes were suppressed by treatment with 25 ng/ml LL-Z1640-2. Thus, LL-Z1640-2 could suppress CdCl(2)-induced activation of JNK/p38 pathways and expression of HSP70 family genes in NIH3T3 cells. LL-Z1640-2 seems to be useful to analyze functions of toxic metal-induced JNK/p38 activation.

Animals↗
PubMed2004

Inhibitory role of endophilin 3 in receptor-mediated endocytosis.

Endophilin 1 (Endo1) participates in synaptic vesicle biogenesis through interactions of its Src homology 3 domain with the polyphosphoinositide phosphatase Synaptojanin and the GTPase Dynamin. Endo1 has also been reported to affect endocytosis by converting membrane curvature via its lysophosphatidic acid acyltransferase activity. Here we report that a closely related isoform of Endo1, Endo3, inhibits clathrin-mediated endocytosis. Mutational analyses showed that the variable region of Endo3 is important in regulating transferrin endocytosis. In the brain, Endo3 is co-localized with dopamine D2 receptor in olfactory nerve terminals and inhibits its clathrin-mediated endocytosis in COS-7 cells. Furthermore, overexpression of Endo3 in an olfactory epithelium-derived cell line suppressed dopamine D2 receptor-mediated endocytosis and therefore accelerated its dopamine-induced differentiation. These results indicate that Endo3 may act as a negative regulator of clathrin-mediated endocytosis in brain neurons.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Acrylamide does not cause apparent changes in genetic expression of creatine kinase in rat cerebellum.

Acrylamide inhibits creatine kinase (CK) activities in the brain of rats or mice. However, its effects on genetic expression of CK have not yet been studied. CK mRNA and protein level were examined by RT-PCR and Western blotting, respectively. Neither cytosolic CK (B subunit) and mitochondrial CK (ubiquitous form) mRNA nor B subunit protein was clearly changed in the cerebellum from rats intoxicated with acrylamide (50 mg/kg/day i.p. for 8 days) and showing clinical neurotoxic signs.

Acrylamide↗
PubMed2004

Decrease of pigment epithelium-derived factor in aqueous humor with increasing age.

PURPOSE: To determine whether the level of pigment epithelium-derived factor (PEDF) in the aqueous humor is altered with age. DESIGN: Observational case series. METHODS: The PEDF concentration in the aqueous humor was measured by enzyme-linked immunosorbent assay in 152 eyes of 121 patients who underwent cataract surgery. RESULTS: The mean aqueous level of PEDF was 0.86 +/- 0.04 microg/ml (mean +/- standard error, 70.7 +/- 1.0 years). The PEDF levels decreased with increasing age, and the decrease was significantly correlated with age (Pearson product moment correlation coefficient, r = - 0.22, P =.006). The mean PEDF level in the men (0.76 +/- 0.06 microg/ml, 53 eyes, 71.5 +/- 2.0 years) was significantly lower than that in women (0.91 +/- 0.04 microg/ml, 99 eyes, 70.2 +/- 1.1 year, P =.03). CONCLUSIONS: The negative correlation of PEDF level and age should be considered in age-related eye diseases, especially those associated with angiogenesis.

Adolescent↗
PubMed2004

Decreased levels of pigment epithelium-derived factor in eyes with neuroretinal dystrophic diseases.

PURPOSE: To determine the concentration of pigment epithelium-derived factor (PEDF) in the aqueous humor of eyes with neuroretinal dystrophy. DESIGN: Observational case series. METHODS: Aqueous humor was obtained from patients during cataract surgery, and the PEDF concentration in the aqueous humor was measured by enzyme-linked immunosorbent assay. The primary diagnosis was cataract in 162 eyes; of these there were five eyes with retinitis pigmentosa, nine eyes with advanced glaucoma, and 148 eyes with cataract alone. RESULTS: The mean levels of PEDF in eyes with retinitis pigmentosa (0.24 +/- 0.04 microg/ml, mean +/- SE, P =.0004) and advanced glaucoma (0.46 +/- 0.08 microg/ml, P =.003) were significantly lower than that in eyes with cataract alone (0.86 +/- 0.04 microg/ml). CONCLUSION: The lower levels of PEDF in eyes with neuroretinal dystrophy may be related to the loss of the retinal ganglion cells or retinal pigment epithelium cells that synthesize PEDF.

Aged↗
PubMed2004

Remodeling of reciprocal synapses associated with persistence of long-term memory.

We investigated a model of long-term memory in which the female mouse establishes pheromonal memory of its partner at mating. We examined the reciprocal synapses of the accessory olfactory bulb and found that pheromonal memory was associated with morphological changes in excitatory synapses in the early phase of memory acquisition and by changes in inhibitory synapses in the late phases of memory persistence. After extinction of pheromonal memory, these morphological changes were no longer present. These findings suggest that the persistence of pheromonal memory is associated with continuous and dynamic changes in the morphological plasticity of reciprocal synapses in the accessory olfactory bulb.

Animals↗
PubMed2004

[Cyanide].

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Acute Disease↗
PubMed2003

Brain-derived neurotrophic factor-dependent unmasking of "silent" synapses in the developing mouse barrel cortex.

Brain-derived neurotrophic factor (BDNF) is a critical modulator of central synaptic functions such as long-term potentiation in the hippocampal and visual cortex. Little is known, however, about its role in the development of excitatory glutamatergic synapses in vivo. We investigated the development of N-methyl-D-aspartate (NMDA) receptor (NMDAR)-only synapses (silent synapses) and found that silent synapses were prominent in acute thalamocortical brain slices from BDNF knockout mice even after the critical period. These synapses could be partially converted to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-containing ones by adding back BDNF alone to the slice or fully converted to together with electric stimulation without affecting NMDAR transmission. Electric stimulation alone was ineffective under the BDNF knockout background. Postsynaptically applied TrkB kinase inhibitor or calcium-chelating reagent blocked this conversion. Furthermore, the AMPAR C-terminal peptides essential for interaction with PDZ proteins postsynaptically prevented the unmasking of silent synapses. These results suggest that endogenous BDNF and neuronal activity synergistically activate AMPAR trafficking into synaptic sites.

Animals↗
PubMed2003

Rapid induction of Arc is observed in the granule cell dendrites in the accessory olfactory bulb after mating.

The activity-regulated cytoskeleton-associated protein (Arc), encoded by the immediate early gene arc, is enriched in the brain and is hypothesized to play a role in the activity-dependent neuronal plasticity in the hippocampus. In the present study, the time course of Arc expression during the post-mating period was determined immunocytochemically, and the localization of Arc in the neurons in the accessory olfactory bulb (AOB) of female mice after mating was analyzed using immunocytochemical electron microscopy. Transient increases in the number of Arc-immunoreactive cells were observed in the glomerular, mitral/tufted cell and granule cell layers of the AOB after mating. In particular, the increase in the granule cell layer was remarkable, and larger than the increases in the other layers. In addition, electron microscopic observation revealed that Arc immunoreactivity was in the dendrites of the granule cells 1.5 h after mating. These results indicate that expression of Arc protein is induced rapidly and transiently in granule cell dendrites after mating. It is postulated that Arc protein has a role in the neuronal plasticity of the AOB after mating.

Animals↗
PubMed2003

Phosphorylation of p53 protein in A549 human pulmonary epithelial cells exposed to asbestos fibers.

We examined effects of asbestos exposure on the phosphorylation of p53 protein in human pulmonary epithelial type II cells (A549), which express wild-type p53. In cells exposed to two different types of asbestos, chrysotile (approximately 1-6% iron content) and crocidolite (approximately 27% iron content) fibers, at the doses of 1, 5, and 10 microg/cm2 for 24 hr, the levels of p53 phosphorylated at Ser15 and p53 protein were correlated with the dose. On a per-weight basis, chrysotile was more potent in inducing Ser15 phosphorylation and accumulation of p53 protein than was crocidolite. After exposure to 10 micro g/cm2 chrysotile, the levels of p53 phosphorylated at Ser15 and of p53 protein increased after 18 hr. Among serines in p53 protein immunoprecipitated from A549 cells treated with chrysotile, only Ser15 was markedly phosphorylated. In contrast, no clear phosphorylation was observed at Ser6, Ser9, Ser20, Ser37, Ser46, or Ser392. Blocking of the extracellular signal-regulated protein kinase pathway with U0126 or inhibition of p38 activity with SB203580 did not suppress chrysotile-induced Ser15 phosphorylation. On the other hand, treatment with wortmannin, an inhibitor of DNA-activated protein kinase and ataxia-telangiectasia mutated, suppressed both chrysotile-induced Ser15 phosphorylation and accumulation of p53 protein. Treatment with either catalase or N-acetylcysteine failed to suppress chrysotile-induced Ser15 phosphorylation, suggesting that reactive oxygen species do not play a major role in the phosphorylation of p53 protein. The present results show that asbestos, particularly chrysotile, induces phosphorylation of p53 protein at Ser15 in A549 cells depending on a DNA damage-signaling pathway.

Asbestos↗
PubMed2002

Mating behavior induces differential Arc expression in the main and accessory olfactory bulbs of adult rats.

The expression of activity-related cytoskeleton-associated protein, Arc, could be useful as a marker for neuronal activity. We investigated Arc-immunoreactivity in both the accessory olfactory bulb (AOB) and the main olfactory bulb (MOB) of adult male rats in response to mating or exposure to female pheromones. Mating behavior strongly enhanced the Arc-immunoreactivity in the granule cell layer of the AOB. However, the enhancement of Arc-immunoreactivity by mating behavior was not observed in the MOB. These results showed that Arc-immunoreactivity was enhanced when the AOB received both afferent and efferent information during mating behavior. Hence, the expression of Arc in the AOB directly associates the pheromonal information with mating behavior. The AOB will provide a useful model to investigate the function of Arc protein.

Analysis of Variance↗
PubMed2002

A comparative immunocytochemical study of development and regeneration of chemosensory neurons in the rat vomeronasal system.

Vomeronasal neurons undergo continuous neurogenesis during development and after neuronal injury. We used immunocytochemical methods to compare different stages of the vomeronasal organ development to those of regeneration following vomeronasal nerve transection. At E15 and at 6 to 10 days after injury, nestin-positive cells were observed throughout the sensory epithelium. We did not find nestin immunoreactivity to be localized to the boundary region of the epithelium. The early appearance and wide distribution of nestin-positive cells suggests that they represent chemosensory precursor cells that develop and migrate vertically in the epithelium. Vomeronasal receptor cells degenerated 6 to 8 days after nerve transection, but axon terminals in the accessory olfactory bulb (AOB) continued to show the presence of the chemosensory specific marker (OMP) for up to ten days, a significant finding observed in this study. It is likely that the distance from the site of nerve transection may contribute to differences in the time course of anterograde and retrograde axon degradation. OMP-positive neurons were observed in the normal adult epithelium and to a much lesser extent 10-60 days after recovery from nerve transection. Axons from regenerated receptor cells did not reach the AOB during this time period. This failure to reestablish connections with target cells in the AOB could explain why OMP-positive cells were rarely observed among the regenerated cells in the vomeronasal epithelium.

Aging↗
PubMed2002

Expression and regulation of the immediate-early gene product Arc in the accessory olfactory bulb after mating in male rat.

Recent studies of the accessory olfactory bulb have shown that the expression of immediate-early genes, e.g., c-fos, c-jun and egr-1, can be used as a marker of neuronal activity in response to pheromonal cues. In this study, we analyzed the expression pattern, in response to mating, of the novel immediate-early gene product Arc (an activity-regulated cytoskeleton-associated protein). Arc is hypothesized to play a role in activity-dependent neuronal plasticity in the hippocampus. In a control group of male rats, only a small number of Arc-immunoreactive cells were observed in the accessory olfactory bulb. In a mating group, however, a marked increase in the number of Arc-immunoreactive cells was observed only in the granule cell layer of the accessory olfactory bulb. The increase in the number of Arc-immunoreactive cells after mating was similar to that observed for other immediate-early genes. However, for the mating group, the increase in Arc-positive cells was limited to the granule cell layer. Granule cells have been shown to exhibit a strong synaptic plasticity in response to pheromonal stimulation. From these findings we suggest that Arc plays an important role in neuronal plasticity in the accessory olfactory bulb.

Animals↗