• 운동영양학회지
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• 제16권2호
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• pp.73-84
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• 2012

Thyroid hormones are important for the development of the brain including the cerebellum. In the present study, we investigated the effect of treadmill exercise on the survival of Purkinje neurons and the activation of astrocytes in the cerebellar vermis of hypothyroidism-induced rat pups. On the day of perinatal 14, pregnant rats were divided into two groups (n = 5 in each group): the pregnant control group and the pregnantmethimazole (MMI)-treated group. For the induction of hypothyroidism in the rat pups, MMI was added to the drinking water (0.02% wt/vol), from the day of perinatal 14 to postnatal 49. After delivery, male rat pups born from the pregnant control group were assigned to the control group. Male rat pups born from the MMI-treated group were divided into the hypothyroidism-induction group, the hypothyroidism-induction with treadmill exercise group, and the hypothyroidism-induction with thyroxine (T4) treatment group (n = 10 in each group). The rat pups in the exercise group were forced to run on a treadmill for 30 min once a day for 4 weeks, starting on postnatal day 22. In the hypothyroidism-induced rat pups, motor coordination was reduced and Purkinje cell death and reactive astrocytes in the cerebellar vermis were increased. Treadmill exercise enhanced motor coordination, increased the survival of Purkinje neurons, down-regulated reactive astrocytes, and enhanced brain-derived neurotrophic factor (BDNF) and receptor tyrosine kinase B (TrkB) expressions in the hypothyroidism-induced rat pups. These results suggest that treadmill exercise has beneficial effects in terms of protecting against thyroid dysfunction by increasing T3 and T4 and the related protein, BDNF, as well as TrkB, inhibition on astrocyte activation and the reduction of Purkinje cell loss regarding the cerebellum in hypothyroidism rat pups.

• The Korean Journal of Physiology and Pharmacology
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• 제16권1호
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• pp.43-48
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• 2012

Glutamate excitotoxicity is emerging as a contributor to degeneration of spinal cord motoneurons in amyotrophic lateral sclerosis (ALS). Recently, we have reported that ghrelin protects motoneurons against chronic glutamate excitotoxicity through the activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol-3-kinase/Akt/glycogen synthase kinase-$3{\beta}$ pathways. Previous studies suggest that activated microglia actively participate in the pathogenesis of ALS motoneuron degeneration. However, it is still unknown whether ghrelin exerts its protective effect on motoneurons via inhibition of microglial activation. In this study, we investigate organotypic spinal cord cultures (OSCCs) exposed to threohydroxyaspartate (THA), as a model of excitotoxic motoneuron degeneration, to determine if ghrelin prevents microglial activation. Exposure of OSCCs to THA for 3 weeks produced typical motoneuron death, and treatment of ghrelin significantly attenuated THA-induced motoneuron loss, as previously reported. Ghrelin prevented THA-induced microglial activation in the spinal cord and the expression of pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ and interleukin-$1{\beta}$. Our data indicate that ghrelin may act as a survival factor for motoneurons by functioning as a microglia-deactivating factor and suggest that ghrelin may have therapeutic potential for the treatment of ALS and other neurodegenerative disorders where inflammatory responses play a critical role.

• Korean Journal of Acupuncture
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• 제24권1호
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• pp.131-144
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• 2007

Objectives : Although the cause of neuronal death of Parkinson's disease remains unclear, increasing evidence points to the role of inflammatory processes. And the hallmark of brain inflammation is the activation of microglia. This study was performed to prove the effect of acupuncture on inhibiting microglial activation. Methods : The rat models which were injected with 6-hydroxydopamine were treated with acupuncture once a day on LR3 (太衝) and GB34 (陽陵泉). To prove the effect of inhibiting microglial activation, we examined the tyrosine hydroxylase (TH) immunopositive neurons and CD11b immunohistochemistry in the substantia nigra. Results : There were 18% (third day), 32% (seventh day) loss of TH-positive cell bodies in the control group and 23% (third day), 26% (seventh day) in the acupuncture group, whereas 3% (third day), 10% (seventh day) in vehicle group. The difference of optical density in substantia nigra was evaluated by subtracting log inverse gray value of contralateral side from that of ipsilateral side. With regards to the result of CD11b immunohistochemistry, acupuncture group showed significantly inhibited microglial activation compared with control group (p<0.01) on the seventh day. Conclusions : Acupuncture showed the effect of inhibition of microglial activation in seventh day. However, the effect of protection of TH positive cell bodies was not shown. So we need longer investigation of the effect of acupuncture on Parkinson's disease.

• 한국식품영양과학회지
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• 제13권2호
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• pp.181-187
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• 1984

Lysine is known as a limiting amino acid in rice. In addition, it is considered to be important in that it is easily non-activated by the browning reaction during processing or storage. The present study was designed to utilize a kinetic approach to analyse the effect of temperature and water activity on available lysine loss in rice. Simplified kinetic models were used to obtain the various kinetic parameters for available lysine loss in rice subjected to accelerated shelf-life tests (ASLT). These kinetic parameters were then used to predict protein quality loss under the non-steady state storage. The predicted losses were compared to the actual losses. As expected, available lysine loss was increased with increased temperature and water activity. The activation energies and $Q_{10}$ values for available lysine loss ranged from 4.03 to 5.10 Kcal/ mole and 1.22 to 1.27, respectively, The shelf-lives at $25^{\circ}C$, the time to reach 25% loss of the available lysine, which was derived from the accelerated shelf-life tests showed 67 to 107 days according to $a_w$'s. The amount of loss for the fluctuating condition was greater than that occurring at the mean temperature of $45^{\circ}C$. Actually, the differences in effective temperature for the fluctuating storage were between about 4 and $6^{\circ}C$. In predicting the extent of loss using constant state data, the predicted shelf-lives were 2 to 7 days shorter than the actual storage values.

• Carbon letters
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• 제24권
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• pp.62-72
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• 2017

The aim of this work was to evaluate the dielectric properties of impregnated and activated palm kernel shells (PKSs) samples using two activating agents, potassium carbonate ($K_2CO_3$) and sodium hydroxide (NaOH), at three impregnation ratios. The materials were characterized by moisture content, carbon content, ash content, thermal profile and functional groups. The dielectric properties were examined using an open-ended coaxial probe method at various microwave frequencies (1-6 GHz) and temperatures (25, 35, and $45^{\circ}C$). The results show that the dielectric properties varied with frequency, temperature, moisture content, carbon content and mass ratio of the ionic solids. PKSK1.75 (PKS impregnated with $K_2CO_3$ at a mass ratio of 1.75) and PKSN1.5 (PKS impregnated with NaOH at a mass ratio of 1.5) exhibited a high loss tangent ($tan{\delta}$) indicating the effectiveness of these materials to be heated by microwaves. $K_2CO_3$ and NaOH can act as a microwave absorber to enhance the efficiency of microwave heating for low loss PKSs. Materials with a high moisture content exhibit a high loss tangent but low penetration depth. The interplay of multiple operating frequencies is suggested to promote better microwave heating by considering the changes in the materials characteristics.

• 대한한방내과학회지
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• 제35권3호
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• pp.317-331
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• 2014

Objectives: The root of Platycodon grandiflorum (PG) has been known to possess a range of pharmacological activities including anti-cancer, anti-inflammatory, and anti-oxidant effects. The present study was designed to investigate whether or not PG-induced cell death was connected with autophagy and apoptosis in NCI-H460 human lung cancer cells. Methods: Effects on the cell viability and apoptotic activity were quantified using MTT assays and flow cytometry analysis, respectively. Protein activation was measured by immunoblotting. Autophagy was measured by LC3 immunofluorescence and immunoblotting. ROS production and loss of mitochondria membrane potential (MMP) were checked with flow cytometry analysis. Results: Following exposure to PG, NCI-H460 cell proliferation decreased simultaneously inducing autophagic vacuoles and up-regulation of microtubule-associated protein 1 light chain 3 and beclin-1 protein expressions. Interestingly, pre-treated with autophagy inhibitors, 3-methyladenin or bafilomycin A1 further triggered reduction of cell viability. PG treatment also induced apoptosis that was related modulation of Bcl-2 family proteins, death receptors and activation of caspases. In addition, PG stimulation clearly enhanced loss of MMP and reactive oxygen species (ROS) generation. Conclusions: Our results suggest that PG elicited both autophagy and apoptosis by increasing loss of MMP and ROS production. PG induced-autophagy may play a cell protective role.

• Biomolecules & Therapeutics
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• 제28권4호
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• pp.337-343
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• 2020

Activation of osteoclast and inactivation of osteoblast result in loss of bone mass with bone resorption, leading to the pathological progression of osteoporosis. The receptor activator of NF-κB ligand (RANKL) is a member of the TNF superfamily, and is a key mediator of osteoclast differentiation. A flavanone glycoside isolated from the fruit of Poncirus trifoliata, poncirin has anti-allergic, hypocholesterolemic, anti-inflammatory and anti-platelet activities. The present study investigates the effect of poncirin on osteoclast differentiation of RANKL-stimulated RAW264.7 cells. We observed reduced formation of RANKL-stimulated TRAP-positive multinucleated cells (a morphological feature of osteoclasts) after poncirin exposure. Real-time qPCR analysis showed suppression of the RANKL-mediated induction of key osteoclastogenic molecules such as NFATc1, TRAP, c-Fos, MMP9 and cathepsin K after poncirin treatment. Poncirin also inhibited the RANKL-mediated activation of NF-κB and, notably, JNK, without changes in ERK and p38 expression in RAW264.7 cells. Furthermore, we assessed the in vivo efficacy of poncirin in the lipopolysaccharide (LPS)-induced bone erosion model. Evaluating the micro-CT of femurs revealed that bone erosion in poncirin treated mice was markedly attenuated. Our results indicate that poncirin exerts anti-osteoclastic effects in vitro and in vivo by suppressing osteoclast differentiation. We believe that poncirin is a promising candidate for inflammatory bone loss therapeutics.

• Molecules and Cells
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• 제24권1호
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• pp.95-104
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• 2007

The mechanism of acacetin-induced apoptosis of human breast cancer MCF-7 cells was investigated. Acacetin caused 50% growth inhibition ($IC_{50}$) of MCF-7 cells at $26.4{\pm}0.7{\mu}M$ over 24 h in the MTT assay. Apoptosis was characterized by DNA fragmentation and an increase of sub-G1 cells and involved activation of caspase-7 and PARP (poly-ADP-ribose polymerase). Maximum caspase 7 activity was observed with $100{\mu}M$ acacetin for 24 h. Caspase 8 and 9 activation cascades mediated the activation of caspase 7. Acacetin caused a reduction of Bcl-2 expression leading to an increase of the Bax:Bcl-2 ratio. It also caused a loss of mitochondrial membrane potential that induced release of cytochrome c and apoptosis inducing factor (AIF) into the cytoplasm, enhancing ROS generation and subsequently resulting in apoptosis. Pretreatment of cells with N-acetylcysteine (NAC) reduced ROS generation and cell growth inhibition, and pretreatment with NAC or a caspase 8 inhibitor (Z-IETD-FMK) inhibited the acacetin-induced loss of mitochondrial membrane potential and release of cytochrome c and AIF. Stress-activated protein kinase/c-Jun $NH_4$-terminal kinase 1/2 (SAPK/JNK1/2) and c-Jun were activated by acacetin but extracellular-regulated kinase 1/2 (Erk1/2) nor p38 mitogen-activated protein kinase (MAPK) were not. Our results show that acacetin-induced apoptosis of MCF-7 cells is mediated by caspase activation cascades, ROS generation, mitochondria-mediated cell death signaling and the SAPK/JNK1/2-c-Jun signaling pathway, activated by acacetin-induced ROS generation.

• Journal of Plant Biotechnology
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• 제34권4호
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• pp.285-291
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• 2007

본 연구는 아그로박테리움 공동배양법을 이용한 기능획득 인삼 모상근의 대량생산을 위한 조건 확립에 대한 것이다. 일반적으로, 인삼과 같이 형질전환을 통한종자의 확보가 어려운 식물에서는 loss-of-function을 이용한 기능유전체 연구에 한계가 있다. 한편, 유전자의 기능을 활성화시키는 방법 (gain-of-function)인 activation tagging 기술은 이러한 문제점을 극복할 수 있는 대안이 될 수 있으며, Agrobacterium rhizogenes를 이용한 모상근 생산 시스템은 대량의 돌연변이체를 안정적으로 용이하게 얻을 수 있다는 점에서 최적의 시스템이라고 할 수 있다. 본 연구에서는 activation-tagging된 효율적인 형질전환 모상근 생산에 있어서의 최적의 아그로박테리움 균주 및 인삼조직, 배지조성 등에 대한 조건을 확립하였으며, 다양한 배지에서의 형질전환 모상근의 생장률 및 분지율, 표현형 등을 조사하였다. 엽병 절편을 activation-tagging vector pKH01을 가지고 있는 A. rhizogenes R1000와 공동배양하였을 때 배양 4주후 85.9%의 빈도로 모상근이 생산되었다. 모상근의 최대 생장과 분지도를 나타내는 배양조건을 조사한 바 엽병절편을 1/2 SH 배지에서 4주 배양하였을 때 왕성하게 생장하였으며 2.6의 분지도를 보여주었다. 최종적으로 1,989개체의 독립적인 형질전환 모상근 line을 생산하였으며, 이들 모상근 line은 인삼 진세노사이드 생합성 관련 유전자의 발굴 및 기능해석에 유용하게 쓰일 것이다.

• Animal cells and systems
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• 제6권2호
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• pp.171-180
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• 2002

Nitric oxide has high affinity for iron, and thus it can cause intracellular iron loss. We tested the idea that intracellular iron can be the primary target of NO toxicity by comparing the signaling mechanisms involved in cell death caused by iron depletion and that caused by NO. Treatment of HL-60 cells with a NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), decreased the intracellular iron level rapidly as that observed with the iron chelator deferoxamine (DFO). Iron chelators such as DFO and mimosine could induce death of human leukemic HL-60 cells by a mechanism requiring activation of p38 kinase, c-Jun N-terminal kinase, caspase-3 and caspase-8. DFO and SNAP also caused release of cytochrome c from mitochondria. Inhibition of p38 kinase by a selective inhibitor, SB203580, abolished the NO and DFO-induced cell death, release of cytochrome c, and activation of caspase-3 and caspase-8, thus indicating that p38 kinase lies upstream in the cell death processes. In a parallel situation, the cells that are sensitive to NO showed similar sensitivity to DFO. Moreover, simultaneous addition of ferric citrate, an iron-containing compound, inhibited the SNAP and DFO-induced activation of caspases and also blocked the NO-mediated cell cycle arrest at $G_1$ phase. Collectively, our data implicate that the NO-induced cell death of tumor cells including HL-60 cells is mediated by depletion of iron and further suggest that activation of p38 kinase lies upstream of cytochrome c release and caspase activation involved in this apoptotic process.