• Molecules and Cells
• /
• v.25 no.1
• /
• pp.55-63
• /
• 2008

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the selective death of motor neurons. Mutations in the SOD1 gene are responsible for a familial form of ALS (FALS). Although many studies suggest that mutant SOD1 proteins are cytotoxic, the mechanism is not fully understood. To investigate the role of mutant SOD1 in FALS, human SOD1 genes were fused with a PEP-1 peptide in a bacterial expression vector to produce in-frame PEP-1-SOD fusion proteins (wild type and mutants). The expressed and purified PEP-1-SOD fusion proteins were efficiently transduced into neuronal cells. Neurones harboring the A4V, G93A, G85R, and D90A mutants of PEP-1-SOD were more vulnerable to oxidative stress induced by paraquat than those harboring wild-type proteins. Moreover, neurones harboring the mutant SOD proteins had lower heat shock protein (Hsp) expression levels than those harboring wild-type SOD. The effects of the transduced SOD1 fusion proteins may provide an explanation for the association of SOD1 with FALS, and Hsps could be candidate agents for the treatment of ALS.

• Molecular & Cellular Toxicology
• /
• v.4 no.2
• /
• pp.106-112
• /
• 2008

Parkinson's disease (PD) progresses severely by a gradual loss of dopaminergic neurons in the substantia nigra (SN). Epidemiological studies showed that the incidences of PD were reduced by smoking of which the major component, nicotine might be neuroprotective. But the function of nicotine, which might suppress the incidences of PD, is still unknown. Fortunately, recently it was reported that a glial reaction and inflammatory processes might participate in a selective loss of dopaminergic neurons in the SN. The levels of tumour necrosis factor (TNF)-${\alpha}$ synthesised by astrocytes and microglia are elevated in striatum and cerebrospinal fluid (CSF) in PD. TNF-${\alpha}$ kills the cultured dopaminergic neurons through the apoptosis mechanism. TNF-${\alpha}$ release from glial cells may mediate progression of nigral degeneration in PD. Nicotine pretreatment considerably decreases microglial activation with significant reduction of TNF-${\alpha}$ mRNA expression and TNF-${\alpha}$ release induced by lipopholysaccharide (LPS) stimulation. Thus, this study was intended to explore the role of nicotine pretreatment to inhibit the expressions of TNF-${\alpha}$ mRNA in human fetal astrocytes (HFA) stimulated with IL-$1{\beta}$. The results are as follows: HFA were pretreated with 0.1, 1, and $10{\mu}g/mL$ of nicotine and then stimulated with IL-$1{\beta}$ (100 pg/mL) for 2h. The inhibitory effect of nicotine on expressions of TNF-${\alpha}$ mRNA in HFA with pretreated $0.1{\mu}g/mL$ of nicotine was first noted at 8hr, and the inhibitory effect was maximal at 12 h. The inhibitory effect at $1{\mu}g/mL$ of nicotine was inhibited maximal at 24 h. Cytotoxic effects of nicotine were noted above $10{\mu}g/mL$ of nicotine. Moreover, Nicotine at 0.1, 1 and $10{\mu}g/mL$concentrations significantly inhibited IL-$1{\beta}$-induced TF-${\kappa}B$ activation. Collectively, these results indicate that in activated HFA, nicotine may inhibit the expression of TNF-${\alpha}$ mRNA through the pathway which suppresses the NF-${\kappa}B$ activation. This study suggests that nicotine might be neuroprotective to dopaminergic neurons in the SN and reduce the incidences of PD.

• Korean Journal of Weed Science
• /
• v.11 no.3
• /
• pp.187-194
• /
• 1991

Absorption and translocation, and metabolism studies using $^{14}C$-naproanilide were conducted to determine selective mode of action of naproanilide in rice and paddy weeds under different temperature conditions. Absorption amount of $^{14}C$-naproanilide was greater in Cyperus serotinus and Sagittaria pygmaea than rice and Echinochloa crusgalli. Especially, absorption of $^{14}C$-naproanilide in C. serotinus was increased twice at 32 $^{\circ}C$ and 48 hour exposure conditions. $^{14}C$-naproanilide in roots was translocated to shoots very little in rice and E. crusgalli, but S. pygmaea somewhat greater translocation than the other species. In C. serotinus and S. pygmaea, susceptible weeds, metabolic rates of naproanilide into phytotoxic NOP (2-(2-naphthoxy)-propionic acid) and NOPM (methyl 2-(2-naphthoxy) propionate) were significantly greater than in rice and E. crugalli, tolerant species. Consequently, differential uptake by roots and the difference in activation metabolism of naproanilide among species may explain the possible mechanism of selectivity.

• Korean Journal of Weed Science
• /
• v.17 no.2
• /
• pp.192-198
• /
• 1997

This experiment was carried out to determine selectivity of herbicide cyhalofop-butyl ester on enzyme activity, biosynthesis of fatty acid and protein between rice and Echinochloa crus-galli. Activity of the acetyl-CoA carboxylase(ACCase) was inhibited greater in E. crus-galli than in rice by the treatment of cyhalofop-butyl ester. The ACCase activity in E. crus-galli was observed with $I_{50}$ at 1-2ppm of cyhalofop-butyl ester, while in rice only at above 10ppm. Cyhalofop-butyl ester also inhibited the biosynthesis of fatty acid by 61% of palmitic acid, 54% of linoleic acid and 41% of linolenic acid in E. crux-galli. In contrast, no significant difference of fatty acid content was observed in rice at 5DAT as compared with the untreated control. Protein patterns of rice between the herbicide treatment and the untreated control were not significantly different, but in E. crus-galli, 3 protein spots were disappeared in between 29KD and 45KD.

• Korean Journal of Poultry Science
• /
• v.16 no.4
• /
• pp.219-232
• /
• 1989

The present study was done to investigate the mechanism of Pancreatic digestive enzyme secretion in response to dietary components in chicks. A simplefied pancreatic juice collection method, useful for a short-term experiment, was developed. By wing vein injection, it was shown that the increased trypsinogen and chymotrypsinogen, while neither other single amino acids nor glucose affected the secretion of enzymes, amylase, trypsinogen and chymotrypsinogen. Cholecystokinin (CCK) had an immediate effect on pancreatic enzyme secretion and this response was in a dose dependent fashion. The injection of CCK seemed to have selective stimulation favoring the secretion of chymotrypsinosen followed by amylase and trypsinogen. Simultaneous injection of single amino acid with CCK increased digestive enzyme secretion to various extents depending on the kind of amino acids whereas the injection of glucose with CCK did not affect when compared with that of CCK'alone. By varying doses, synergetic action of CCK plus amino acid on the secretion of pancreatic digestive enzymes was observed at 0.5mM for Val and 5mM for Arg. A further attempt was made to examine the effect of combined administration of amino acids with CCK on pancreatic enzyme secretion. The injected substances were an AAs mixture and combination of selected amino acids, i.e. Thr＋Phe＋Ile, Thr＋Phe. Thr＋Ile or Phe＋Ile. When increases in enzyme outputs for the first 30 min were compared , it was shown that the responses of three enzymes, amylase, trypsinogen and chymotrypsinogen, brought about by the administration of the AAs mixture was almost entirely accounted for by the combined injection of Thr＋Phe. Thus, it was well demonstrated that CCK and amino acids had a synergetic action on the secretion of a specific pancreatic digestive enzyme depending on a kind of amino acid injected.

• The Journal of Engineering Geology
• /
• v.20 no.2
• /
• pp.183-189
• /
• 2010

Fault gouge samples were collected from the fault cores of the boundary faults between the Cretaceous Basement and the Tertiary Waeup Basin. Fractal dimensions (D) were obtained by using survivor grains which were analysed from six thin sections of the gouges under the optical microscope. The elliptical survivor grains show a shape preferred orientation almost parallel to clay foliation in matrix, suggesting that it was formed by the rotation of the survivor grains in abundant fine-grained matrix during repeated fault slips. The size distributions of the survivor grains follow power-laws with fractal dimensions in the 2.40-3.02 range. D values of all samples but one are higher than a specific D value equal to 2.58 which predicts the self similarity of fragmentation process in constrained comminution model (Sammis et al., 1987), which indicates large fault slip and multiple faulting. Probably the higher D values than 2.58 mean the non-self-similar evolution of cataclastic rocks where fragmentation mechanism changed from constrained comminution to the grain abrasion accompanying selective fracture of larger grains.

• Journal of Microbiology and Biotechnology
• /
• v.21 no.12
• /
• pp.1345-1351
• /
• 2011

Vancomycin therapy failure due to the emergence of tolerance in pneumococci is increasing. The molecular mechanism of tolerance is not clear, but lytA and $pep^{27}$ are known to be involved. Our aim was to evaluate the expression of both genes in vancomycin-tolerant Streptococcus pneumoniae (VTSP) strains. Eleven VTSP strains from a total of 309 clinical isolates of S. pneumoniae from 1997 to 2006 were classified according to the criteria of Liu and Tomasz. All VTSP strains were evaluated for susceptibility according to CLSI criteria, serotype by the Quellung test, and clonality by PFGE. The expressions of lytA and $pep^{27}$ were analyzed in different growth phases by RT-PCR with and without vancomycin. Eighty-two percent of VTSP strains showed resistance to penicillin, and 100% were sensitive to vancomycin and cefotaxime. The most frequent serotypes of VTSP strains were 23F (4/11) and 6B (3/11). Clonal relationship was observed in only two strains. No significant changes were observed in $pep^{27}$ expression in the three phases of growth in VTSP strains with and without vancomycin. Interestingly, $pep^{27}$ expression in the stationary phase in the non-tolerant reference strain R6 was significantly higher. However, no significant differences in lytA expression were observed between VTSP and R6 strains during the phases of growth analyzed. The absence of changes in $pep^{27}$ expression in VTSP strains in the stationary phase may be related to their ability to tolerate high antibiotic concentrations, and thus, they survive and remain in the host under the antibiotic selective pressure reflected in therapeutic failure.

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.3
• /
• pp.309-316
• /
• 2017

Transient receptor potential vanilloid 3 (TRPV3) is a non-selective cation channel with modest permeability to calcium ions. It is involved in intracellular calcium signaling and is therefore important in processes such as thermal sensation, skin barrier formation, and wound healing. TRPV3 was initially proposed as a warm temperature sensor. It is activated by synthetic small-molecule chemicals and plant-derived natural compounds such as camphor and eugenol. Schisandra chinensis (Turcz.) Baill (SC) has diverse pharmacological properties including antiallergic, anti-inflammatory, and wound healing activities. It is extensively used as an oriental herbal medicine for the treatment of various diseases. In this study, we investigated whether SC fruit extracts and seed oil, as well as four compounds isolated from the fruit can activate the TRPV3 channel. By performing whole-cell patch clamp recording in HEK293T cells overexpressing TRPV3, we found that the methanolic extract of SC fruit has an agonistic effect on the TRPV3 channel. Furthermore, electrophysiological analysis revealed that ${\gamma}$-schisandrin, one of the isolated compounds, activated TRPV3 at a concentration of $30{\mu}M$. In addition, ${\gamma}$-schisandrin (${\sim}100{\mu}M$) increased cytoplasmic $Ca^{2+}$ concentrations by approximately 20% in response to TRPV3 activation. This is the first report to indicate that SC extract and ${\gamma}$-schisandrin can modulate the TRPV3 channel. This report also suggests a mechanism by which ${\gamma}$-schisandrin acts as a therapeutic agent against TRPV3-related diseases.

• The Korean Journal of Physiology and Pharmacology
• /
• v.4 no.3
• /
• pp.185-195
• /
• 2000

Vascular diseases are significant complications of diabetes mellitus (DM), and the endothelial cells may play a pivotal role in the development of vascular disease in DM. Endothelin-1 (ET-1) released from endothelium is a potent vasoconstrictor peptide and circulating level of ET-1 is increased in a variety of disease states. The purpose of this study was to determine the changes of responsiveness to ET-1 in DM, and we experimented on the changes in the ET-1-induced contraction, levels of nitrite and lipid peroxidation, and ET-1 immunoreactivity in aorta from streptozotocin-induced DM rats. DM was induced by single injection of streptozotocin (55 mg/kg, i.p.). The immunoreactive ET-1 levels in endothelial layer of thoracic aorta were much higher in DM rats than control rats. Nitrite in tissue homogenate was decreased and plasma nitrite was increased in DM rats. Malondialdehyde (MDA) was significantly increased in DM rats and cGMP was not significantly different between control and DM rats. ET-1 produced concentration- dependent contractile responses that are significantly attenuated in DM rats compared to controls. In the presence of selective $ET_A$ receptor antagonist BQ610, the maximum contraction was decreased and the concentration ratios for BQ610 yielded $pA_2$ values of 7.3 (slope, 0.65) in control rats, whereas BQ610 had no antagonistic effect on ET-1-induced contraction in DM rats. However, pretreatment with BQ788, an $ET_B$ receptor antagonist, maximum response was decreased and the dose-response curves for ET-1 were shifted to the right in both groups and $pA_2$ values were 7.9 and 7.7 (slope, 1.05 in control and DM rats), respectively. IRL 1620 and sarafotoxin S6c, $ET_B$ agonists, induced relaxation in control rats but not in DM rats. These results indicate that endothelial cell dysfunction and enhanced immunoreactivity of ET-1 have been found in DM rat and ET-1-induced contraction was attenuated in DM rat. These attenuated responses might be at least in part caused by the alteration of $ET_A$ receptor properties (e.g. desensitization), and partly related with an alteration in intracellular mechanism for contraction to ET-1.

• The Korean Journal of Physiology and Pharmacology
• /
• v.13 no.6
• /
• pp.517-526
• /
• 2009

The present study was attempted to investigate whether polyphenolic compounds isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect the release of catecholamines (CA) from the isolated perfused adrenal medulla of the spontaneously hypertensive rats (SHRs), and to establish its mechanism of action. PCRC $(20\sim180\;{\mu}g/ml)$ perfused into an adrenal vein for 90 min relatively dose-dependently inhibited the CA secretory responses to ACh (5.32 mM), high $K^+$ (56 mM), DMPP $(100\;{\mu}M)$ and McN-A-343 $(100\;{\mu}M)$. PCRC itself did not affect basal CA secretion (data not shown). Also, in the presence of PCRC $(60\;{\mu}g/ml)$, the CA secretory responses to veratridine (a selective $Na^+$ channel activator $(10\;{\mu}M)$, Bay-K-8644 (a L-type dihydropyridine $Ca^{2+}$ channel activator, $10\;{\mu}M$), and cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, $10\;{\mu}M$) were significantly reduced, respectively. In the simultaneous presence of PCRC $(60\;{\mu}g/ml)$ and L-NAME (an inhibitor of NO synthase, $30\;{\mu}M$), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high $K^+$, DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with that of PCRC-treatment alone. The level of NO released from adrenal medulla after the treatment of PCRC $(60\;{\mu}g/ml)$ was greatly elevated compared with the corresponding basal level. Taken together, these results demonstrate that PCRC inhibits the CA secretion from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is mediated by blocking the influx of calcium and sodium into the adrenal medullary chromaffin cells of the SHRs as well as by inhibition of $Ca^{2+}$ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of NO synthase.