• Biomolecules & Therapeutics
• /
• v.17 no.4
• /
• pp.379-387
• /
• 2009

We have previously reported that N-ethylmaleimide (NEM) induces apoptosis through activation of $K^+$, $Cl^-$-cotransport (KCC) in HepG2 human hepatoblastoma cells. In this study we investigated the possible role of phospholipase $A_2$ ($PLA_2$)-arachidonic acid (AA) signals in the mechanism of the NEM-induced apoptosis. In these experiments we used arachidonyl trifluoromethylketone ($AACOCF_3$), bromoenol lactone (BEL) and p-bromophenacyl bromide (BPB) as inhibitors of the calcium-dependent cytosolic $PLA_2$ ($cPLA_2$), the calcium-independent $PLA_2$ ($iPLA_2$) and the secretory $PLA_2$ ($sPLA_2$), respectively. BEL significantly inhibited the NEM-induced apoptosis, whereas $AACOCF_3$ and BPB did not. NEM increased AA liberation in a dose-dependent manner, which was markedly prevented only by BEL. In addition AA by itself induced $K^+$ efflux, a hallmark of KCC activation, which was comparable to that of NEM. The NEM-induced apoptosis was not significantly altered by treatment with indomethacin (Indo) and nordihydroguaiaretic acid (NDGA), selective inhibitors of cyclooxygenase (COX) and lipoxygenase (LOX), respectively. Treatment with AA or 5,8,11,14-eicosatetraynoic acid (ETYA), a non-metabolizable analogue of AA, significantly induced apoptosis. Collectively, these results suggest that AA liberated through activation of $iPLA_2$ may mediate the NEMinduced apoptosis in HepG2 cells.

• The Korean Journal of Physiology and Pharmacology
• /
• v.7 no.6
• /
• pp.303-306
• /
• 2003

Metabotropic glutamate receptors (mGluRs), classified into three groups (group I, II, III), play a critical role in modulation of synaptic transmission at central and peripheral synapses. In the present study, extracellular field potential recording techniques were used to investigate effects of mGluR agonists on excitatory synaptic transmission at thalamic input synapses onto the lateral amygdala. The non-selective mGluR agonist t-ACPD ($100{\mu}M$) produced reversible, short-term depression, but the group III mGluR agonist L-AP4 ($50{\mu}M$) did not have any significant effects on amygdala synaptic transmission, suggesting that group I and/or II mGluRs are involved in the modulation by t-ACPD. The group I mGluR agonist DHPG ($100{\mu}M$) produced reversible inhibition as did t-ACPD. Unexpectedly, the group II mGluR agonist LCCG-1 ($10{\mu}M$) induced long-term as well as short-term depression. Thus, our data suggest that activation of group I or II mGluRs produces short-term, reversible depression of excitatory synaptic transmission at thalamic input synapses onto the lateral amygdala. Considering the long-term effect upon activation of group II mGluRs, lack of long-term effects upon activation of group I and II mGluRs may indicate a possible cross-talk among different groups of mGluRs.

• The Korean Journal of Physiology and Pharmacology
• /
• v.14 no.5
• /
• pp.299-304
• /
• 2010

Losartan is a selective angiotensin II (Ang II) type 1 ($AT_1$) receptor antagonist which inhibits vascular smooth muscle cells (VSMCs) contraction and proliferation. We hypothesized that losartan may prevent cell proliferation by activating AMP-activated protein kinase (AMPK) in VSMCs. VSMCs were treated with various concentrations of losartan. AMPK activation was measured by Western blot analysis and cell proliferation was measured by MTT assay and flowcytometry. Losartan dose- and time-dependently increased the phosphorylation of AMPK and its downstream target, acetyl-CoA carboxylase (ACC) in VSMCs. Losartan also significantly decreased the Ang II- or 15% FBS-induced VSMC proliferation by inhibiting the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. Compound C, a specific inhibitor of AMPK, or AMPK siRNA blocked the losartan-induced inhibition of cell proliferation and the $G_0/G_1$ cell cycle arrest. These data suggest that losartan-induced AMPK activation might attenuate Ang II-induced VSMC proliferation through the inhibition of cell cycle progression.

• Physical Therapy Korea
• /
• v.16 no.2
• /
• pp.31-39
• /
• 2009

This study is performed to investigate the difference of the spinal stability system with and without low back pain. There were 9 participants with low back pain and 9 asymptomatic subjects to be recruited, they were measured thoracic and lumbar curvature, trunk muscle activation in upright sitting postures and slump sitting, back muscle endurance, and lumbar proprioception. Spinal curvature and surface electromyography of 4 trunk muscles were measured in an upright sitting postures and slump sitting in 18 subjects. The result of the study was that there were significant differences between the groups in spinal curvature (p<.05), significantly higher external oblique activity and less internal oblique in the low back pain group than the healthy subjects (p<.05), and significantly less proprioception in the low back pain group (p<.05). But there was not a significant difference between the trunk muscle endurance groups. According to the result, the low back pain group had greater thoracic extension and higher global muscle activity in the upright sitting posture and less proprioception. This study was useful to suggest postural training for normal muscle activation, selective muscle strengthening to prevent chronic deterioration, and helpful in making a treatment plan to indicate a synthetic care method that includes increasing proprioception.

• Radiation Oncology Journal
• /
• v.34 no.4
• /
• pp.239-249
• /
• 2016

Tumor hypoxia, a common feature occurring in nearly all human solid tumors is a major contributing factor for failures of anticancer therapies. Because ionizing radiation depends heavily on the presence of molecular oxygen to produce cytotoxic effect, the negative impact of tumor hypoxia had long been recognized. In this review, we will highlight some of the past attempts to overcome tumor hypoxia including hypoxic radiosensitizers and hypoxia-selective cytotoxin. Although they were (still are) a very clever idea, they lacked clinical efficacy largely because of 'reoxygenation' phenomenon occurring in the conventional low dose hyperfractionation radiotherapy prevented proper activation of these compounds. Recent meta-analysis and imaging studies do however indicate that there may be a significant clinical benefit in lowering the locoregional failures by using these compounds. Latest technological advancement in radiotherapy has allowed to deliver high doses of radiation conformally to the tumor volume. Although this technology has brought superb clinical responses for many types of cancer, recent modeling studies have predicted that tumor hypoxia is even more serious because 'reoxygenation' is low thereby leaving a large portion of hypoxic tumor cells behind. Wouldn't it be then reasonable to combine hypoxic radiosensitizers and/or hypoxia-selective cytotoxin with the latest radiotherapy? We will provide some preclinical and clinical evidence to support this idea hoping to revamp an enthusiasm for hypoxic radiosensitizers or hypoxia-selective cytotoxins as an adjunct therapy for radiotherapy.

• Journal of the Korean Recycled Construction Resources Institute
• /
• v.11 no.3
• /
• pp.251-259
• /
• 2023

In this study, as a foundational research aimed at promoting the efficient recycling and environmentally friendly disposal of construction waste through the activation of a selective dismantling system, our primary objective was to analyze the economic feasibility of implementing selective dismantling. To achieve this, we conducted an assessment on a 5-story residential building with a construction area of 2,400 m² as a case study. When considering the additional cost of dismantling construction ① the reduction in waste disposal costs due to decreased mixed waste, ② and the potential revenue from recycling through the separation and sorting of waste materials, and ③ we were able to comprehensively confirm that there is an expected cost-saving effect totaling 34,727,000 KRW when compared to conventional demolition methods.

• The Korean Journal of Physiology and Pharmacology
• /
• v.6 no.3
• /
• pp.165-169
• /
• 2002

We have previously demonstrated that phytoestrogens isolated from safflower seeds significantly attenuated bone loss in ovariectomized rats, and directly stimulated proliferation and differentiation of cultured osteoblastic cells. In an attempt to elucidate underlying cellular mechanisms, in the present study we investigated effects of $17{\beta}-estradiol\;(E_2)$ and phytoestrogens such as matairesinol and acacetin, a type of lignan and flavonoid, respectively, on activation of mitogen activated protein (MAP) kinases, extracellular signal-regulated kinase 1 (ERK1) and ERK2, in cultured osteoblastic ROS 17/2.8 cells. Western blot analysis with anti-MAP kinase antibody showed that a wide range concentrations $(10^{-14}\;to\;10^{-6}\;M)\;of\;E_2$ as well as both phytoestrogens induced rapid and transient activation of ERK1/2 through phosphorylation within minutes. Maximum activation of MAP kinases by $E_2$ and phytoestrogens were observed at 10 and 15 min, respectively. $E_2-induced$ phosphorylation of ERK1/2 returned to the control level at 30 min, whereas phytoestrogen-induced phosphorylation was maintained at high level until 30 min. PD-98059, a highly selective inhibitor of MAP kinase, prevented phosphorylation of ERK1/2 in the cells treated either with $E_2$ or phytoestrogens. To examine a possible involvement of estrogen receptor in the activation process of MAP kinase, Western blot analysis was performed in the presence and absence of the estrogen receptor antagonists, ICI 182,780 and tamoxifen. These antagonists blocked MAP kinase phosphorylation induced not only by $E_2,$ but also by the phytoestrogens. To the best our knowledge, this study is the first to demonstrate that phytoestrogens such as flavonoid and lignan extracted from safflower seeds produce a rapid activation of MAP kinase, at least partially via membrane estrogen receptor of the cultured osteoblastic cells.

• The Korean Journal of Physiology and Pharmacology
• /
• v.12 no.2
• /
• pp.37-41
• /
• 2008

Melatonin has been reported to protect neurons from a variety of neurotoxicity. However, the underlying mechanism by which melatonin exerts its neuroprotective property has not yet been clearly understood. We previously demonstrated that melatonin protected kainic acid-induced neuronal cell death in mouse hippocampus, accompanied by sustained activation of Akt, a critical mediator of neuronal survival. To further elucidate the neuroprotective action of melatonin, we examined in the present study the causal mechanism how Akt signaling pathway is regulated by melatonin in a rat primary astrocyte culture model. Melatonin resulted in increased astrocytic Akt phosphorylation, which was significantly decreased with wortmannin, a specific inhibitor of PI3K, suggesting that activation of Akt by melatonin is mediated through the PI3K-Akt signaling pathway. Furthermore, increased Akt activation was also significantly decreased with luzindole, a non-selective melatonin receptor antagonist. As downstream signaling pathway of Akt activation, increased levels of CREB phoshorylation and GDNF expression were observed, which were also attenuated with wortmannin and luzindole. These results strongly suggest that melatonin exerts its neuroprotective property in astrocytes through the activation of plasma membrane receptors and then PI3K-Akt signaling pathway.

• The Korean Journal of Physiology and Pharmacology
• /
• v.17 no.1
• /
• pp.51-56
• /
• 2013

Many intracellular proteins and signaling cascades contribute to the sensitivity of N-methyl-D-aspartate receptors (NMDARs). One such putative contributor is the serine/threonine kinase, protein kinase C (PKC). Activation of PKC by phorbol 12-myristate 13-acetate (PMA) causes activation of extracellular signal-regulated kinase (ERK) and promotes the formation of new spines in cultured hippocampal neurons. The purpose of this study was to examine which PKC isoforms are responsible for the PMA-induced augmentation of long-term potentiation (LTP) in the CA1 stratum radiatum of the hippocampus in vitro and verify that this facilitation requires NMDAR activation. We found that PMA enhanced the induction of LTP by a single episode of theta-burst stimulation in a concentration-dependent manner without affecting to magnitude of baseline field excitatory postsynaptic potentials. Facilitation of LTP by PMA (200 nM) was blocked by the nonspecific PKC inhibitor, Ro 31-8220 ($10{\mu}M$); the selective $PKC{\delta}$ inhibitor, rottlerin ($1{\mu}M$); and the $PKC{\varepsilon}$ inhibitor, TAT-${\varepsilon}V1$-2 peptide (500 nM). Moreover, the NMDAR blocker DL-APV ($50{\mu}M$) prevented enhancement of LTP by PMA. Our results suggest that PMA contributes to synaptic plasticity in the nervous system via activation of $PKC{\delta}$ and/or $PKC{\varepsilon}$, and confirm that NMDAR activity is required for this effect.

• Environmental Analysis Health and Toxicology
• /
• v.18 no.2
• /
• pp.121-129
• /
• 2003

The genotoxicity of pendimethalin [N-(l-ethylpropyl)-2, 6-dinitro-3, 4-xylidine, C$\_$13/H$\_$19/N$_3$O$_4$, M.W.=281.3, CAS No. 40487-42-1], one of selective herbicide, was evaluated in bacterial gene mutation system, chromosome aberration in mammalian cell system and in vivo micronucleus assay with rodent. In bacterial gene mutation assay, pendimethalin revealed dose-dependent mutagenic potential in 313 ∼ 5,000 ${\mu}$g/plate of Salmonella typhimurium TA 98 and TA 1537 both in the absence and presence of S-9 metabolic activation system, and TA 100 only in the absence of S-9 mixture. In the TA 1535, slight increase of revertant was also observed in the presence of S-9 metabolic activation system. No mutagenic potential was observed in the TA 1535 without metabolic activation system and TA l00 in the presence of S-9 mixture. In mammalian cell system using Chinese hamster lung (CHL) fibroblast, no clastogenicity of pendimethalin was observed both in the absence and presence of S-9 metabolic activation system in the concentration range of 2.32∼9.28 ${\mu}$g/ml. And also, in vivo bone marrow micronucleus assay, pendimethalin revealed no clastogenic potential in the dose range of 203∼810 mg/kg body weight after oral administration in mice. Consequently, in vitro chromosome aberration with mammalian cells and in vivo bone marrow micronucleus assay revealed no clastogenic potential of pendimethalin. However, pendimethalin revealed mutagenic potential in bacterial gene mutation assay.