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Biomedical subjects

Tae-Cheon Kang

Publications and source records attributed to Tae-Cheon Kang.

At least 109 records · Page 6Linked to original sources

Nerve growth factor induces proliferation of PC12 cells through Cdc42.

Nerve growth factor (NGF) can change neurite outgrowth and cellular morphology of rat adrenal pheochromocytoma PC12 cells. In the present study, stable PC12 cells with constitutively active form (L61Cdc42), the dominant negative constructs (N17Cdc42), and wild type Cdc42 did not proliferate in low serum condition. However, on exposure to NGF, PC12 cells transfected with L61Cdc42 cDNA proliferated, whereas wild type Cdc42 and N17Cdc42 cDNA-transfected PC12 cells did not. When the cells were stimulated with NGF, ERK1/2 was transiently activated in L61Cdc42-transfected PC12 cells, whereas the activation of ERK1/2 was sustained in other cell lines. NGF repressed the induction of p21WAF1, cyclin-dependent kinase (CDK) inhibitor, in L61Cdc42 transfected PC12 cells, whereas NGF induced the expression of p21WAF1 in other PC12 cell lines.

Animals↗

Human liver catalase: cloning, expression and characterization of monoclonal antibodies.

We isolated a cDNA encoding liver catalase from a human liver cDNA library. The cDNA had a high degree of sequence similarity to the corresponding enzyme from other sources. It was expressed in E. coli using the pET15b vector. The protein produced was enzymatically active after purification, and its kinetic parameters closely resembled those of other mammalian catalases. Monoclonal antibodies were generated against the purified catalase; six antibodies recognizing different epitopes were obtained, one of which inhibited the enzyme. The cross reactions of the antibodies with brain catalases from human and other mammalian tissues were investigated, and all the immunoreactive bands obtained on Western blots had molecular masses of about 58 kDa. Similarly fractionated extracts of several mammalian cell lines all gave a single band of molecular mass 58 kDa. These results indicate that mammalian livers and human cell lines contain only one major type of immunologically reactive catalase, even though some of catalases have been previously reported to differ in certain properties.

Amino Acid Sequence↗

The evidence for GABAB receptor-mediated regulation of acid-base balance: involvement of Na+/H+ exchanger and Na+/HCO3- cotransporter.

A comparative analysis of the effects of gamma-aminobutyric acid (GABA) on the expressions of Na+/H+ exchanger 1 (NHE1) and Na+/HCO3- cotransporter (NBC) was investigated in order to extend our understanding of the mechanism of GABA receptor-mediated acid-base balance using a gerbil model. In vigabatrin (VGB, GABA degradation inhibitor) treated gerbils, both NHE1 and NBC immunoreactivities in the hippocampus were significantly elevated, as compared with the controls. Analogous to VGB treatment, baclofen (GABAB receptor agonist) treatment also evoked elevations of both NHE1 and NBC expressions in the hippocampus, whilst their expressions were unaffected by muscimol (GABAA receptor agonist) treatment. Therefore, our findings suggest that GABAB receptor-mediated regulation of NHE1 and NBC expressions may participate in acid-base balance in the gerbil hippocampus.

Acid-Base Equilibrium↗

Chronological alterations of calbindin D-28k immunoreactivity in the gerbil main olfactory bulb after ischemic insult.

We investigated spatial and temporal alterations of calbindin D-28k (CB) immunoreactivity in the gerbil main olfactory bulb after transient ischemia-reperfusion. In sham-operated animals, CB-immunoreactive (IR) neurons were found in the periglomerular layer, external plexiform layer and granule cell layer. At 1-4 days after ischemic insult, the number of CB-IR neurons significantly increased. This result suggests that the increased CB may buffer the intracellular calcium at an early time point after the ischemic insult. In contrast, 10-30 days after the ischemic insult, the number of CB-IR neurons significantly decreased as compared to sham-operated animals. This result suggests that a malfunction in olfactory process may have occurred in the olfactory bulb at a later time point after the ischemic insult.

Animals↗

Accumulation of microtubule-associated proteins in the hippocampal neurons of seizure-sensitive gerbils.

We have carried out a chronological and comparative analysis of microtubule-associated protein 1A (MAP1A) and microtubule-associated protein 2 (MAP2) immunoreactivities in the hippocampi of seizure-resistant (SR) and seizure-sensitive (SS) gerbils. These animals represent excellent genetic models of epilepsy associated with different sequelae of spontaneous seizures. Both MAP1A and MAP2 immunoreactivities were detected in the granule cell layer and in the hilar neurons of SR gerbils. In contrast with the SR gerbils, some neurons containing MAPs immunoreactivities were scattered in the molecular layer of the dentate gyrus as well as being concentrated in the hilar neurons in the SS gerbils. An increase in MAP1A immunoreactivity was evident in the perikarya of the dentate gyrus at 30 min postictal, whereas MAP2 immunoreactivity decreased. MAP1A immunoreactivity in the hilar neurons declined significantly by 3 h postictal, whereas MAP2 immunoreactivity increased. These results suggest that the immunoreactivity of MAPs in the hippocampal complex differs between SR and SS gerbils, and that this difference may be the results of seizure activity.

Animals↗

Temporal alterations in voltage gated Ca2+ channel immunoreactivities in the gerbil hippocampus following ischemic insults.

In the present study, temporal changes of voltage-gated Ca(2+) channel (VGCC) immunoreactivities were evaluated in the gerbil hippocampus following ischemia. P/Q-type VGCC immunoreactivity was elevated in the hippocampus in the 3 h post-ischemic group. In the 30 min post-ischemic group, N-type VGCC immunoreactivity began to increase only in the CA1 region. L-type (alpha1C) VGCC immunoreactivity was significantly increased in the 12 h post-ischemic group. L-type (alpha1D) VGCC immunoreactivity began to increase in the CA1 region in the 30 min post-ischemic group and peaked in the 12 h post-ischemic group. These findings suggest that the altered VGCC immunoreactivities following ischemia may play an important role in the ischemic neuronal injury.

Animals↗

Effect of vigabatrin on glutamate dehydrogenase in the hippocampus of seizure prone gerbils.

Vigabatrin (VGB, gamma-vinyl-gamma-aminobutyric acid (GABA)), an irreversible inhibitor of GABA transaminase, increases regional inhibitory effects by elevating GABA concentration and reducing glutamate synthesis. In the present study, changes in glutamate dehydrogenase (GDH) activity and its immunoreactivity in the seizure prone gerbil hippocampus after treating VGB were investigated to identify the effect of VGB on energy and/or glutamate metabolism via GDH. In the VGB treated group, GDH immunoreactivity and its activity in the hippocampus were significantly decreased, as compared with those of controls. These findings suggest that VGB administration may suppress the development and spread of seizures not only by elevating the level of GABA, but also by affecting the glutamate signaling and energy metabolism in neurons.

Animals↗

Gastrodin decreases immunoreactivities of gamma-aminobutyric acid shunt enzymes in the hippocampus of seizure-sensitive gerbils.

Gastrodin is one of the natural compound isolated from Gastrodia elata and has known anticonvulsant effects, although the exact pharmacological principles of this natural compound and its effects on other aspects of gamma-aminobutyric acid (GABA) metabolism in vivo have not been explored. Therefore, in the present study, the effects of gastrodin on GABA metabolism in the gerbil hippocampus were examined, in an effort to identify the antiepileptic characteristics of this substance. Gastrodin reduced the seizure score in the treated group, although the immunoreactivities of GABA synthetic enzymes and GABA transporters were unaltered in gastrodin-treated animals. Interestingly, in the gastrodin-treated group, GABA transaminase (GABA-T) immunoreactivity in the hippocampus, particularly in neurons, was significantly decreased. In the gastrodin-treated group, both succinic semialdehyde dehydrogenase (SSADH) and succinic semialdehyde reductase (SSAR) immunoreactivities in the hippocampus was also decreased significantly, which stood in contrast to the nontreated group, in which strong SSADH and SSAR immunoreactivities were detected. From the neuroanatomical viewpoint, these findings suggest that gastrodin may cause the elevation of GABA concentration by inhibiting the GABA shunt.

Animals↗

The differential expression of corticotropin releasing factor and its binding protein in the gerbil hippocampal complex following seizure.

Considerable attention has been focused on the role of corticotropin releasing factor (CRF) as well as CRF-binding protein (CRF-BP) in neuropsychiatric disorders and neurodegenerative diseases including epilepsy. Therefore, in the present study, we investigated the temporal and spatial alteration of CRF and CRF-BP in the gerbil hippocampal complex in order to characterize the possible changes and associations with different sequelae of spontaneous seizure in these animals. CRF immunoreactivity was shown in the interneurons of the hippocampal complex at 30 min following seizure. Additionally, alteration of CRF-BP immunoreactivity was restricted to the entorhinal cortex after seizure. These results indicate some factors for consideration. First, in the gerbil hippocampal complex, the delayed increase of CRF immunoreactivity, in spite of its excitatory function, may attenuate seizure activity, but may not do so in epileptogenesis. Second, in contrast to the hippocampal complex, the increase in CRF-BP immunoreactivity in the entorhinal cortex following seizure may participate in feedback inhibitory modulation.

Animals↗

The altered expression of GABA shunt enzymes in the gerbil hippocampus before and after seizure generation.

In the present study, the distribution of succinic semialdehyde dehydrogenase (SSADH) and succinic semialdehyde reductase (SSAR) in the hippocampus of the Mongolian gerbil and its association with various sequelae of spontaneous seizure were investigated in order to identify the roles of GABA shunt in the epileptogenesis and the recovery mechanisms in these animals. Both SSADH and SSAR immunoreactivities in the GABAergic neurons were significantly higher in the pre-seizure groups of seizure sensitive (SS) gerbil as compared to those seen in the seizure resistant (SR) gerbils. The distributions of both SSADH and SSAR immunoreactivities in the hippocampus showed significant differences after the on-set of seizure. At 3 h postictal, when compared to the pre-seizure group of SS gerbils, a decline in the immunoreactivities in the perikarya was observed. At 12 h after seizure on-set, the densities of both SSADH and SSAR immunoreactivities were begun to recover to the pre-seizure level of SS gerbils. These results suggest that the GABAergic neurons in the hippocampal complex of the SS gerbil may be highly activated. In addition, the imbalance of GABA shunt expressions in the GABAergic neurons may imply a malfunction of the metabolism of GABAergic neurons in the SS gerbils, and this defect may trigger seizure on-set. Therefore, the initiation of seizure, at least in gerbils, may be the result of a malfunction in GABA shunt in the GABAergic neurons.

Aldehyde Oxidoreductases↗

Altered corticotropin-releasing factor (CRF) receptor immunoreactivity in the gerbil hippocampal complex following spontaneous seizure.

Considerable attention has been focused on the role of corticotropin-releasing factor (CRF) in neuropsychiatric disorders and neurodegenerative diseases including epilepsy. Therefore, in the present study, we investigated the temporal and spatial alteration of CRF receptor in the gerbil hippocampal complex in order to characterize the possible changes and associations with different sequelae of spontaneous seizure in these animals. Thirty minutes postictal, a decline in CRF receptor immunoreactivity was observed in the granule cells and hilar neurons. In the subiculum, CRF receptor immunoreactivity was also significantly decreased at this time point. Twenty-four hours after seizure onset, the immunoreactivity in these regions recovered to the pre-seizure level. Moreover, 30 min after seizure in the entorhinal cortex, the density of CRF receptor immunoreactivity began to decrease, particularly in the layers II and III, compared to pre-seizure group. Nevertheless, 24h after seizure onset, CRF receptor immunodensity had recovered to its seizure-sensitive (SS) level. These results suggest that altered CRF receptor expression in the hippocampal complex may affect tissue excitability and seizure activity in SS gerbils.

Animals↗

Morphological characteristics of dopaminergic immunoreactive neurons in the olfactory bulb of the common marmoset monkey (Callithrix jacchus).

The present study describes the distribution of tyrosine hydroxylase (TH)-immunoreactive (IR) elements in the olfactory bulb of the common marmoset monkey (Callithrix jacchus), a primate species by immunohistochemistry. We identified six layers of the olfactory bulb of the common marmoset monkey in sections stained with cresyl violet. The majority of TH-IR cells were found in the glomerular layer. A few TH-IR cells were present in the external plexiform and granule cell layers. TH-IR fibers were identified in all layers of the olfactory bulb. The density of these nerve fibers was high in the internal plexiform and granule cell layers. The results in the olfactory bulb of the common marmoset monkey are generally similar to previous reports in some mammals. These data suggest that TH in the olfactory bulb of the common marmoset monkey may play a role in olfactory transmission via the glomeruli like in other mammals.

Animals↗

Alterations in Na+/H+ exchanger and Na+/HCO3- cotransporter immunoreactivities within the gerbil hippocampus following seizure.

In this study, a chronological and comparative analysis of the immunoreactivities of Na(+)/H(+) exchanger 1 (NHE1), Na(+)/HCO(3)(-) cotransporter (NBC) and Na(+)/Ca(2+) exchanger (NCE) was conducted in order to identify the effects of spontaneous seizure on their protein expression levels using the gerbil model. The distribution of NHE1 and NBC immunoreactivity in the hippocampus of seizure-resistant (SR) gerbils was similar to that observed in the pre-seizure group of seizure-sensitive (SS) gerbils. From 30 min to 3 h after the onset of the seizure, both NHE1 and NBC immunoreactivities were elevated in the hippocampus, as compared to the pre-seizure group of SS gerbils. At 6 h postictal, these immunoreactivities in the hippocampus had reduced to the pre-seizure level. However, NCE immunoreactivity within the hippocampus was unaltered. These findings suggest that the changes in both NHE1 and NBC immunoreactivity within the hippocampus following seizure may affect tissue excitability and play a role in the reduction of the seizure activity in the gerbil.

Animals↗

Spatial and temporal alterations in the GABA shunt in the gerbil hippocampus following transient ischemia.

In the present study, we have identified the alteration in the expressions of GABA shunt-associated enzymes and the GABA transporter in order to determine the relationship between the neuronal damage and GABA metabolism following ischemia. At 30 min post-ischemia, the immunoreactivities of the glutamic acid decarboxylase (GAD) isoforms were markedly elevated in the CA1 region, as compared with the sham operated group. At 3-12 h post-ischemia, their immunoreactivities recovered at the sham level. These patterns were similarly observed up to 12 h following ischemia insult. However, the intensity of GAD67 was markedly increased at 24 h post-ischemic insult. The temporal changes in GABA transporter 1 (GAT-1) expressions were similar to that of GAD67, but not GAD65, expression, at least prior to 12 h after ischemic insults. GAT-1 immunoreactivity was significantly elevated in the CA1 region posterior to 12 h post-ischemia. Both succinic semialdehyde dehydrogenase (SSADH) and succinic semialdehyde reductase (SSAR) immunoreactivities were not altered in GABAergic neurons following ischemia. In contrast, in pyramidal cells, both SSADH and SSAR immunoreactivities showed chronological alterations in the CA1 region. Thus, our findings suggest that the differential alterations of GABA metabolism may be one of the important factors in neuronal damages induced by ischemia.

Aldehyde Oxidoreductases↗

Age-related change of calbindin D-28k immunoreactive neurons in the rat main olfactory bulb.

We examined the aged-related changes of calbindin D-28k (CB)-immunoreactive (IR) neurons in the rat main olfactory bulb (MOB). The localization of CB-IR neurons was found to be almost entirely restricted to the glomerular layer. However, a few CB-IR neurons were observed in the granular layer. Prior to the 6th postnatal month (PM 6), the CB-IR neurons had long processes, and the population of CB-IR neurons had increased significantly compared to PM 12 and 24. At PM 12, CB-IR neurons showed a tendency to be smaller and have fewer dendrites than at guess. This phenomenon became remarkable at PM 24. The distinct reduction of CB-IR dendrites in glomeruli may be due to age-related functional restrictions. Increased calcium levels in the MOB neurons may be induced to allow cytotoxic event detection in the MOB neurons, and unbalanced Ca(2+)/Mg(2+)-ATPase may also induce aging-related MOB morphological changes.

Aging↗

Oxidative DNA damage and alteration of glutamate transporter expressions in the hippocampal Ca1 area immediately after ischemic insult.

Although oxidative stress and excitotoxicity may be interdependent mechanisms that are involved in delayed neuronal death, the temporal participation of these events in the early stage after ischemia-reperfusion insult is unclear. Therefore, in the present study, using the gerbil global ischemic model we investigated whether oxidative stress could be correlated with the expression of the glutamate transporters in the hippocampus, and whether these events are related and cooperate in the events that link ischemia to neuronal death in vivo. Thirty minutes after ischemia, the intensities of glutamate transporter-1 (GLT-1), glutamate/aspar-tate transporter (GLAST), and 8-hydroxy2'-deoxy-guanosine (8-OHdG) immunoreactivities were markedly increased in the hippocampal CA1 area. In contrast, excitatory amino acid carrier-1 (EAAC-1) immunoreactivity was 30% lower in the CA1 area than in the sham level. At 3 h post-reperfusion, the EAAC-1 expression began to increase in the CA1 area. Twelve hours after reperfusion, the reduction of both GLT-1 and GLAST immunoreactivity was salient, while the EAAC-1 immunoreactivity level intensified significantly. The 8-OHdG immunoreactivity peaked at this time point. These findings suggest that oxidative stress and alterations in the glutamate transporter expression in the CA1 area may simultaneously trigger neuronal damages very early after ischemia.

Amino Acid Transport System X-AG↗

Carnosine and related dipeptides protect human ceruloplasmin against peroxyl radical-mediated modification.

Ceruloplasmin (CP) is the major plasma antioxidant and copper transport protein. In a previous study, we showed that the aggregation of human ceruloplasmin was induced by peroxyl radicals. We investigated the effects of antioxidant dipeptides carnosine, homocarnosine and anserine on peroxyl radical-mediated ceruloplasmin modification. Carnosine, homocarnosine and anserine significantly inhibited the aggregation of CP induced by peroxyl radicals. When CP was incubated with peroxyl radicals in the presence of three compounds, ferroxidase activity, as measured by the activity staining method, was protected. All three compounds also inhibited the formation of dityrosine in peroxyl radicals-treated CP. The results suggest that carnosine and related compounds act as peroxyl radical scavenger to protect the protein modification. It is proposed that carnosine and related peptides might be explored as potential therapeutic agents for pathologies that involve CP modification mediated by peroxyl radicals generated in the lipid peroxidation.

Anserine↗

Chronological changes in pyridoxine-5'-phosphate oxidase immunoreactivity in the seizure-sensitive gerbil hippocampus.

To identify the roles of pyridoxine-5'-phosphate (PNP) oxidase in epileptogenesis and the recovery mechanisms in spontaneous seizure, a chronological and comparative analysis of PNP oxidase expression was conducted. PNP oxidase immunoreactivity in a preseizure group of seizure-sensitive (SS) gerbils was detected more strongly than that in a seizure-resistant (SR) group. The density of PNP oxidase immunoreactivity in a 30 min postictal group was significantly lower than that in a preseizure group. In a 12 hr postictal group, PNP oxidase immunodensity had recovered to a preseizure level. The overexpression of PNP oxidase in the hippocampus of preseizure SS gerbils suggests that PNP or pyridoxal 5'-phosphate plays an important role in the modulation of glutamic acid decarboxylase activity and gamma-aminobutyric acid reuptake as mediated by membrane transporter via neurons. In addition, this change in the PNP oxidase immunoreactivity following seizure may be a compensatory response designed to reduce epileptic activity in this animal.

Animals↗