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H Hatanaka

Publications and source records attributed to H Hatanaka.

At least 163 records · Page 9Linked to original sources
PubMed1995

Cultured basal forebrain cholinergic neurons from postnatal rats show both overlapping and non-overlapping responses to the neurotrophins.

Basal forebrain cholinergic neurons respond in vitro and in vivo to nerve growth factor (NGF) and to brain-derived neurotrophic factor (BDNF). It is not clear to what extent the neurons that respond to these two factors, or to neurotrophin-3 or -4/5 (NT-3; NT-4/5) are identical or only partially overlapping populations. We have addressed this issue in cultures of basal forebrain neurons derived from 2-week-old postnatal rats, using choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) as cholinergic markers. Cholinergic neuron survival was enhanced in the presence of NGF, BDNF and NT-4/5. NT-4/5 was as effective as BDNF. NT-3 was without effect at this age, although in cultures derived from embryonic forebrain, cholinergic differentiation was induced by NT-3. Cotreatment with NGF and BDNF resulted in small, but consistent increases in the number of ChAT-positive neurons, compared with either factor alone. NT-4/5 was also found to be additive with NGF, whereas cotreatment with BDNF and NT-4/5 showed no additivity. NT-3 had no additive effects with any other neurotrophin on any cholinergic parameters in postnatal cultures. Taken together, the results indicate the existence in postnatal rat brain of a large overlapping population of cholinergic neurons that are responsive to ligands for the neurotrophin receptors TrkA (NGF) and TrkB (BDNF and NT-4/5), but not TrkC (NT-3), and small distinct populations that show specificity for NGF or BDNF but not both. We hypothesize that cholinergic neurons projecting into different regions of the hippocampus may derive trophic support from distinct neurotrophins.

Acetylcholinesterase↗
PubMed1995

Brain-derived neurotrophic factor (BDNF) can prevent apoptosis of rat cerebellar granule neurons in culture.

Cerebellar granule neurons obtained from 9-day-old rats were grown in vitro for 4 days in high K+ (26 mM) medium. The culture medium was then replaced with that containing low K+ (5 mM) which caused a large number of granule neurons to die. The death of granule neurons has been characterized as apoptosis. In this study, we investigated the effects of various neurotrophins on neuronal survival using the above system. We found that brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5) but not nerve growth factor (NGF) can protect these neurons from apoptosis in low K+. Neurotrophin-3 (NT-3) had a small effect on neuronal survival as reported. To determine whether the granule neurons respond directly to BDNF, we analyzed the induction of the Fos protein in these neurons. Individual cells that synthesize Fos protein after exposure to neurotrophin can be recognized using antibodies to Fos. Immunocytochemical staining of the cultures demonstrated that a relatively large number of cerebellar granule neurons showed immunoreactivity in response to BDNF, but few of them were immunoreactive in the absence of BDNF or in the presence of NGF. Our results suggested that BDNF has a direct effect on mature cerebellar granule neurons and can protect these neurons from apoptosis in low K+.

Animals↗
PubMed1995

Interleukin-1 beta enhances survival and interleukin-6 protects against MPP+ neurotoxicity in cultures of fetal rat dopaminergic neurons.

To investigate the relationships between the central nervous system and interleukins, ventral mesencephalic cells from embryonic 17-day-old rats were cultured for 3 days in vitro (DIV) and exposed to interleukin-1 beta (IL-1 beta), interleukin-3 (IL-3), or interleukin-6 (IL-6) for the following 2 or 3 DIV with or without 2 microM 1-methyl-4-phenylpyridinium (MPP+). Thus, the survival of and the MPP+ neurotoxicity against the dopaminergic neurons immunostained with anti-tyrosine hydroxylase antibody were examined. For the survival studies, IL-1 beta has been shown to have a survival-promoting effect on dopaminergic neurons. This effect is initiated at a concentration between 0.1 and 1 ng/ml. In contrast to the effect of IL-1 beta, IL-3 and IL-6 failed to increase the survival of dopaminergic neurons. In MPP+ neurotoxicity analysis, only IL-6 among the three interleukins studied here has been shown to attenuate the MPP+ neurotoxicity against dopaminergic neurons in a dose-dependent manner; this neuro-protective action is apparent at a concentration of 10 ng/ml. In addition, these three interleukins did not promote glial proliferation. These findings suggest that the effects of IL-1 beta and IL-6 on dopaminergic neurons are not mediated by glial proliferation, that IL-1 beta acts as a neurotrophic factor on dopaminergic neurons, and that IL-6 is capable of protecting dopaminergic neurons from the neurotoxicity of MPP+.

1-Methyl-4-phenylpyridinium↗
PubMed1995

Solution structure of cysteine-rich domain of protein kinase C alpha.

The three-dimensional structure of the second cysteine-rich domain of protein kinase C alpha (residues 95-159) was determined in aqueous solution by two-dimensional proton nuclear magnetic resonance and simulated annealing based calculations. On the basis of 687 distance constraints derived from assigned nuclear Overhauser effect (NOE) connectivities, a total of 10 converged structures were obtained from 40 runs of calculations. The atomic root-mean-square (RMS) difference about the mean coordinate positions (excluding residues 1-7, 16-17, 30-34, and 55-65) is 0.55 A for backbone atoms (N, C alpha, C') and 1.07 A for all non-hydrogen atoms. The molecular scaffold is maintained by triple-stranded and double-stranded twisted beta-sheets packed against an alpha-helix and two independent zincs are coordinated by His8, Cys38, Cys41, Cys57 and Cys21, Cys24, His46, Cys49, respectively. It should be noted that the metal ligands from the two sites are interleaved and this is thought to be a new structural motif of a zinc finger domain. Based on the resultant structure, we propose an interaction site of the cysteine-rich domain of protein kinase C with diacylglycerols and phorbol esters.

Amino Acid Sequence↗
PubMed1995

Survival of and 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity against dopaminergic neurons in coculture of rat mesencephalon with their target on non-target regions.

It is known that dopaminergic neurons in the substantia nigra of the mesencephalon mainly project to the corpus striatum and neocortex, while the hippocampus receives major cholinergic projection from the septum. In the present study, the ventral mesencephalon was cocultured with target regions of its dopaminergic neurons, the striatum and neocortex, and with non-target regions, the hippocampus, thalamus, colliculus and cerebellum, using embryonic day-17 (E17) rats. Thus, the effects of coculture on the survival and the 1-methyl-4-phenylpyridnium (MPP+) neurotoxicity of dopaminergic neurons were investigated. The numbers of viable dopaminergic neurons were enhanced in coculture not only with corpus striatum or neocortex, but also with hippocampus or cerebellum. However, the survival of dopaminergic neurons cocultured with thalamus and colliculus were almost the same as those of controls. These findings suggest that putative factor(s), possibly target-derived neurotrophic factor(s), emerging from the regions cocultured with ventral mesencephalon can influence the dopaminergic neurons resulting in the augmentation of survival. Cocultivation with all the regions studied failed to protect dopaminergic neurons from MPP+ neurotoxicity. The results suggest that even though the survival of dopaminergic neurons was supported by coculture, the action of MPP+, an exogeneous substance, surpassed the supporting capacity of the coculture conditions.

1-Methyl-4-phenylpyridinium↗
PubMed1995

[Clinicopathological report of cisplatin encephalopathy].

A 61-year-old woman was treated with cisplatin and etoposide for ovarian carcinoma. After the second course of chemotherapy she developed acute encephalopathy which manifested itself as headache, fever, a partial seizure, confusion, and mild right hemiparesis, although no evidence of a central nervous system infection was found. Ten days after the onset of neurological symptoms, she experienced a sudden loss of vision in both eyes. Neurological findings were compatible with cortical blindness. Neurological symptoms subsided and visual acuity completely returned over the next months. The total cumulative dose of cisplatin was 325 mg/m2. She died of aspiration pneumonia on the 43rd day. Postmortem examination revealed severe nerve cell loss, gliosis and spongy changes in the bilateral occipital cortex including visual field, and slight to moderate demyelination in the subcortical white matter of the occipital cortex, Goll's tract, and dorsal root ganglia. As far as we know this encephalopathy is the second report in which the neuropathological changes associated with cisplatin therapy have been demonstrated by autopsy findings. The first was a case report of leukoencephalopathy, which differed significantly from our case in the primary lesions of the brain. We measured the platinum level in several parts of the cerebrum and cerebellum, optic nerve, spinal cord, and cauda equina by using an atomic absorption spectrophotometric technique. Platinum was detected in the bilateral occipital cortex, spinal cord, and cauda equina. These results were consistent with the distribution of pathological lesions. The mechanism of cisplatin-induced focal encephalopathy remains speculative.(ABSTRACT TRUNCATED AT 250 WORDS)

Blindness↗
PubMed1994

Solution structure of human insulin-like growth factor II; recognition sites for receptors and binding proteins.

The three-dimensional structure of human insulin-like growth factor II was determined at high resolution in aqueous solution by NMR and simulated annealing based calculations. The structure is quite similar to those of insulin and insulin-like growth factor I, which consists of an alpha-helix followed by a turn and a strand in the B-region and two antiparallel alpha-helices in the A-region. However, the regions of Ala1-Glu6, Pro31-Arg40 and Thr62-Glu67 are not well-defined for lack of distance constraints, possibly due to motional flexibility. Based on the resultant structure and the results of structure-activity relationships, we propose the interaction sites of insulin-like growth factor II with the type 2 insulin-like growth factor receptor and the insulin-like growth factor binding proteins. These sites partially overlap with each other at the opposite side of the putative binding surface to the insulin receptor and the type 1 insulin-like growth factor receptor. We also discuss the interaction modes of insulin-like growth factor II with the insulin receptor and the type 1 insulin-like growth factor receptor.

Amino Acid Sequence↗
PubMed1994

Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2.

BACKGROUND: Growth factor receptor-bound protein 2 (GRB2) is an adaptor protein with three Src homology (SH) domains in the order SH3-SH2-SH3. Both SH3 domains of GRB2 are necessary for interaction with the protein Son of sevenless (Sos), which acts as a Ras activator. Thus, GRB2 mediates signal transduction from growth factor receptors to Ras and is thought to be a key molecule in signal transduction. RESULTS: The three-dimensional structure of the carboxy-terminal SH3 domain of GRB2 (GRB2 C-SH3) was determined by NMR spectroscopy. The SH3 structure consists of six beta-strands arranged in two beta-sheets that are packed together perpendicularly with two additional beta-strands forming the third beta-sheet. GRB2 C-SH3 is very similar to SH3 domains from other proteins. The binding site of the ligand peptide (VPP-PVPPRRR) derived from the Sos protein was mapped on the GRB2 C-SH3 domain indirectly using 1H and 15N chemical shift changes, and directly using several intermolecular nuclear Overhauser effects. CONCLUSIONS: Despite the structural similarity among the known SH3 domains, the sequence alignment and the secondary structure assignments differ. We therefore propose a standard description of the SH3 structures to facilitate comparison of individual SH3 domains, based on their three-dimensional structures. The binding site of the ligand peptide on GRB2 C-SH3 is in good agreement with those found in other SH3 domains.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Sustained tyrosine phosphorylation of p140trkA in PC12h-R cells responding rapidly to NGF.

The PC12h cell, a subclone of PC12 cells, has considerable activities of tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) and shows an NGF-induced increase in both enzyme activities. The TH activity and its inducibility by NGF in PC12h cells were stably maintained in the passage of > 200 generations whereas the ChAT activity was not. We isolated a new cell line, PC12h-R (originally clone 8), from a long-term culture of PC12h cells. PC12h-R cells still showed the considerable TH activity, but not the ChAT activity, and maintained the inducibility of TH activity by NGF. Thus, the responses of PC12h-R cells to NGF were similar to those of chromaffin cells and sympathetic neurons. PC12h-R cells were found to extend neurites and differentiate into sympathetic neuron-like cells in response to NGF much more rapidly than PC12h cells. In addition, PC12h-R cells showed sustained NGF-induced tyrosine phosphorylation of p140trkA and several cellular proteins, including 42-, 44- and 54-kDa proteins, in comparison with PC12h cells. We suggest that the NGF-induced sustained tyrosine phosphorylation signal in PC12h-R cells may be correlated closely with their rapid NGF-induced differentiation into neuron-like cells.

Animals↗
PubMed1994

High potassium and cyclic AMP analog promote neuronal survival of basal forebrain cholinergic neurons in culture from postnatal 2-week-old rats.

We found depolarization-dependent promotion of survival of cultured basal forebrain cholinergic neurons from postnatal 2-week-old rats. Over 30 mM KCl (high K+) as well as nerve growth factor (NGF) induced considerably high choline acetyltransferase (ChAT) activity and the increase was potentiated by the addition of BAY K8644, a Ca2+ channel agonist. The increase in ChAT activity by high K+ was due to the increased number of viable acetylcholinesterase-positive and ChAT-positive neurons. Also, a cyclic AMP analog gave the same effect as high K+, but its ability to induce the ChAT activity was higher than that of high K+. On the other hand, both high K+ and NGF had very little effects on the survival of the cultured cholinergic neurons from 10-week-old rats. Cyclic AMP analog induced considerable increase in ChAT activity and promotion of survival of cholinergic neurons in the 10-week-old culture. These findings showed that the neuronal death occurring just of the end of synapse formation in rat basal forebrain cholinergic neurons could be prevented by NGF and high K+, but the death of older cholinergic neurons could not. We propose the possibility that the death of postnatal 2-week-old basal forebrain cholinergic neurons in culture might be programmed cell death.

Acetylcholine↗
PubMed1994

Solution structure of the epidermal growth factor-like domain of heregulin-alpha, a ligand for p180erbB-4.

p185erbB-2 and p180erbB-4 are epidermal growth factor (EGF) receptor-like tyrosine kinases, whose co-expression is observed in many breast carcinomas. Heregulins (HRGs), which contain an immunoglobulin unit and an EGF-like domain, bind to p180erbB-4 and activate p180erbB-4 and p185erbB-2 through transphosphorylation or receptor heterodimerization. The EGF-like domain is sufficient for the activation. Despite the sequence similarity, no cross activity is seen between the p180erbB-4 ligands (HRGs) and the p170erbB-1 ligands [EGF and transforming growth factor (TGF)-alpha]. To investigate the structural basis of receptor specificity, we have determined the solution structure of the EGF-like domain of HRG-alpha by two-dimensional 1H nuclear magnetic resonance spectroscopy and simulated annealing calculations. Though its main-chain fold is similar to those of EGF and TGF-alpha, distinctive structural features are observed on the molecular surface including an ionic cluster and hydrophobic patches, which afford HRG-alpha the specific affinity for p180erbB-4. The structure should provide a basis for the structure-activity relationship of HRGs and for the design of drugs which prevent progression of breast cancer.

Amino Acid Sequence↗
PubMed1994

Tertiary structure of erabutoxin b in aqueous solution as elucidated by two-dimensional nuclear magnetic resonance.

The three-dimensional structure of erabutoxin b, a short-chain neurotoxic peptide purified from the venom of the sea snake Laticauda semifasciata, was determined in aqueous solution by two-dimensional proton nuclear magnetic resonance and simulated annealing-based calculations. On the basis of 883 assigned nuclear Overhauser effect (NOE) connectivities, 676 final distance constraints were derived and used together with 38 torsion angle (phi, chi 1) constraints, four distance constraints derived from disulfide bridges and 30 distance constraints derived from hydrogen bonds. A total of 14 converged structures were obtained from 50 runs of calculations. The atomic root-mean-square difference about the mean coordinate positions (excluding the residues 18 to 22) is 0.60 A for backbone atoms (N, C alpha and C'). The protein consists of a core region from which three finger-like loops emerge outwards. It includes a short, two-stranded antiparallel beta-sheet of residues 2 to 5 and 13 to 16, a three-stranded antiparallel beta-sheet involving residues 23 to 30, 35 to 41 and 50 to 56, and four disulfide bridges in the core region. Comparison with two crystal structures of erabutoxin b at 1.4 A and 1.7 A resolution indicated that the solution and the crystal structures were very similar, but less defined regions were observed at the localized region of the tip of the central loop and the outside of the third loop in solution. Other short-chain alpha-neurotoxins showed structural characteristics similar to those of erabutoxin b.

Amino Acid Sequence↗
PubMed1994

Interleukin-6 protects cultured rat hippocampal neurons against glutamate-induced cell death.

We examined the effect of interleukin-6 (human recombinant) on glutamate-induced neuronal death of cultured 20-day fetal rat hippocampal neurons. After 7 days in culture, the hippocampal neurons were markedly degenerated by the addition of L-glutamate and also N-methyl-D-aspartate. The neuronal death was prevented by the addition of MK801, a potent N-methyl-D-aspartate antagonist. Interleukin-6 at the concentration of 50 ng/ml has a significant preventive effect on the glutamate-induced neuronal death. Basic fibroblast growth factor at the concentration of 100 ng/ml gave also significant protective effect on hippocampal neurons, but nerve growth factor was ineffective in preventing the toxicity. It has been postulated that glutamate plays an important role in the pathogenesis of neuronal death such as ischemia and the various neurological diseases. Interleukin-6 might have somewhat physiological or pathological role in these events.

Animals↗
PubMed1994

Enhancement of choline acetyltransferase activity in coculture of rat septal and hippocampal neurons.

We report that choline acetyltransferase (ChAT) activity and neuronal survival were enhanced in rat septal neurons cocultured with hippocampal neurons. The enhancement of ChAT activity also occurred as a result of the addition of hippocampal conditioned medium (HpCM). When septal neurons from embryonic day 17 (E17) rats were cocultured with hippocampal neurons, ChAT activity was increased 2-fold compared with homogeneous culture of septal neurons. By contrast, no increase in ChAT activity was observed in coculture of septal and neocortical neurons. Treatment with HpCM obtained from cultured E19 rat hippocampal neurons enhanced the ChAT activity of E17 rat septal neurons. The enhancement of ChAT activity caused by coculture with hippocampal neurons and that caused by the addition of HpCM were not blocked by the addition of anti-nerve growth factor (NGF) antibody, suggesting that NGF, which is known to increase the ChAT activity of septal neurons both in vivo and in vitro, did not participate in the increase of ChAT activity. These findings indicate that possible target-derived neurotrophic factor(s), other than NGF, from hippocampal neurons enhance(s) the ChAT activity of septal neurons.

Animals↗
PubMed1994

Clinical results of long-surviving brain tumor patients who underwent boron neutron capture therapy.

PURPOSE: The present report is a review of long-term survivors in the patients with malignant brain tumors treated by boron neutron capture therapy. METHODS AND MATERIAL: One-hundred twenty patients with 119 intracranial tumors and one extracranial nerve-related tumor were treated by the current standard technique of boron-neutron capture therapy (BNCT) as of December 1992, using 10B-sodium-mercaptoundecahydrododecaborate. RESULTS: Out of 87 patients operated on before May 1987, 18 lived or have lived longer than 5 years. Nine of these 18 lived or have lived longer than 10 years out of 53 patients operated on before May 1982. Among more-than-10-year survivors, only two died at 17 and 12 years. All of the other are still alive. The two died of delayed radiation damage because BNCT was applied to glioblastomas which recurred after their conventional radiotherapy. They lacked evidence of tumors when they died. Out of these nine more-than-10-year survivors, three had been previously treated by conventional external radiotherapy and they developed radiation damage which brought all patients ultimately to an incapacitated condition. Two of the three died. All the other 6 who were free from previous radiation history are active in their jobs and have no evidence of tumors. CONCLUSION: It can be suggested that BNCT is a radiotherapy that can produce "cure" of both malignant and benign brain tumors while preserving a good quality of life if conducted without conventional radiotherapy.

Adult↗
PubMed1994

Nerve growth factor induces trkA mRNA expression in cultured basal forebrain cholinergic neurons from 17-day fetal rats.

We first examined the basal forebrain tissues for developmental changes in expression of the high-affinity NGF receptor (trkA) gene. Our reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed that trkA mRNA is present in those tissues of postnatal rats, but not in those of fetal rats. Then we determined the effect of NGF on trkA gene expression in serum-free cultures of basal forebrain neurons from 17-day fetal rats. NGF was found to induce trkA mRNA 36 h after the addition of NGF, while no trkA mRNA was detected in the absence of NGF.

Animals↗
PubMed1994

Crystal structure of the fungal peroxidase from Arthromyces ramosus at 1.9 A resolution. Structural comparisons with the lignin and cytochrome c peroxidases.

The crystal structure of the peroxidase (donor: H2O2 oxidoreductase, EC 1.11.1.7) from the hyphomycete Arthromyces ramosus (ARP) has been determined by the multiple isomorphous replacement method and refined by the simulated annealing method to a crystallographic R-factor of 17.4% for the 19,191 reflections with F > 2 sigma F between 7.0 and 1.9 A resolution. The model includes residues 9 to 344, the heme group, two N-acetylglucosamine residues, two calcium ions and 246 water molecules. The root-mean-square deviation of bond lengths from the ideal values is 0.02 A. The mean coordinate error is estimated as 0.2 A. The electron density of the glycine-rich region of the amino-terminal eight residues was invisible. ARP has ten major and two short alpha-helices and a few short beta-strands. The overall tertiary structure of ARP is similar to that of yeast cytochrome c peroxidase (CCP) and is particularly similar to that of the lignin peroxidase (LiP) from Phanerochaete chrysosporium. Relative to CCP, ARP and LiP each have an extension of approximately 40 residues at the carboxy terminus. All eight cysteine residues in ARP form disulfide bonds (C12:C24, C23:C293, C43:C129 and C257:C322). Two calcium sites are inaccessible to solvent. The four disulfide bonds and two calcium sites, which are lacking in CCP, are conserved in ARP and LiP. The bond from Asn304C to Ala305N in ARP is the site sensitive to proteases. An Asx turn present in the Asn303 to Ala305 segment appears to orient the side-chain of Asn304 to outward from the molecule, rendering it easily trappable by pockets of proteases. The proximal heme ligand is His184 in helix F (distance of N epsilon 2 ... Fe, 2.10 A), and one of several water molecules in the distal pocket of the heme bridges the iron atom and the N epsilon 2 of His56. The orientation of the imidazole ring of the distal histidine residue relative to the heme group in ARP differs significantly from that in LiP. The access channel to the distal side of the heme of ARP is markedly wider along the heme plane than that of LiP. Many of the amino acid residues that comprise the entrance of this channel differ for ARP and LiP. This may account for the differences in substrate specificity.

Acetylglucosamine↗