• 제목/요약/키워드: pathway extension

검색결과 46건 처리시간 0.035초

Expression of peroxisome proliferator activated receptor gamma in the neuronal cells and modulation of their differentiation by PPAR gamma agonists

  • Hong, Jin-Tae
    • 한국환경성돌연변이발암원학회:학술대회논문집
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    • 한국환경성돌연변이발암원학회 2002년도 Molecular and Cellular Response to Toxic Substances
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    • pp.14-40
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    • 2002
  • 15-Deoxy-${\Delta}^{12, 14}$-prostaglandin $J_2$ (15-deoxy-$PGJ_2$), a naturally occurring ligand activates the peroxisome proliferator-activated $receptor-{\gamma}(PPAR-{\gamma}$). Activation of $PPAR-{\gamma}$ has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-$PGJ_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-$PGJ_2$ (0.2 to 1.6 ${\mu}M$) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/ml). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-$PGJ_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-$PGJ_2$(0.8 ${\mu}M$) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-$PGJ_2$ on the expression of p38 MAP kinase and activation of AP-1, The promoting ability of 15-deoxy-$PGJ_2$ did not occur through $PPAR-{\gamma}$, as synthetic PPAR-${\gamma}$ agonist andantagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), $PPAR-{\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and $PGE_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of f 5-deoxy-$PGJ_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-$PGJ_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 single pathway may be important in the promoting activity of 15-deoxy-$PGJ_2$ cells.

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Expression of peroxisome proliferator activated receptor gamma in the neuronal cells and modulation of their differentiation by PPAR gamma agonists

  • Hong, Jin-Tae
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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    • pp.14-40
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    • 2002
  • 15-Deoxy- Δ$\^$12,14/-prostaglandin J$_2$ (15-deoxy-PGJ$_2$), a naturally occurring ligand activates the peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$). Activation of PPAR-y has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-PGJ$_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-PGJ$_2$ (0.2 to 1.6 ${\mu}$M) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/$m\ell$). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-PGJ$_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-PGJ$_2$ (0.8 ${\mu}$M) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-PGJ$_2$ on the expression of p38 MAP kinase and activation of AP-1. The promoting ability of 15-deoxy-PGJ$_2$ did not occur through PPAR-${\gamma}$, as synthetic PPAR-${\gamma}$ agonist and antagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), PPAR-${\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and PGE$_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of 15-deoxy-PGJ$_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-PGJ$_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 signal pathway may be important in the promoting activity of 15-deoxy-PGJ$_2$ on the differentiation of PC12 cells.

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Innate Immune-Enhancing Effect of Pinus densiflora Pollen Extract via NF-κB Pathway Activation

  • Sehyeon Jang;San Kim;Se Jeong Kim;Jun Young Kim;Da Hye Gu;Bo Ram So;Jung A Ryu;Jeong Min Park;Sung Ran Yoon;Sung Keun Jung
    • Journal of Microbiology and Biotechnology
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    • 제34권3호
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    • pp.644-653
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    • 2024
  • Considering the emergence of various infectious diseases, including the coronavirus disease 2019 (COVID-19), people's attention has shifted towards immune health. Consequently, immune-enhancing functional foods have been increasingly consumed. Hence, developing new immune-enhancing functional food products is needed. Pinus densiflora pollen can be collected from the male red pine tree, which is commonly found in Korea. P. densiflora pollen extract (PDE), obtained by water extraction, contained polyphenols (216.29 ± 0.22 mg GAE/100 g) and flavonoids (35.14 ± 0.04 mg CE/100 g). PDE significantly increased the production of nitric oxide (NO) and reactive oxygen species (ROS) but, did not exhibit cytotoxicity in RAW 264.7 cells. Western blot results indicated that PDE induced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. PDE also significantly increased the mRNA and protein levels of cytokines and the phosphorylation of IKKα/β and p65, as well as the activation and degradation of IκBα. Additionally, western blot analysis of cytosolic and nuclear fractions and immunofluorescence assay confirmed that the translocation of p65 to the nucleus after PDE treatment. These results confirmed that PDE increases the production of cytokines, NO, and ROS by activating NF-κB. Therefore, PDE is a promising nutraceutical candidate for immune-enhancing functional foods.

Combined BOLD fMRI and Transcranial Magnetic Stimulation Study: Evaluation of Ipsilateral Motor Pathway of Stroke Patients

  • 배성진;장용민;장성호;변우목;강덕식
    • 대한자기공명의과학회:학술대회논문집
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    • 대한자기공명의과학회 2001년도 제6차 학술대회 초록집
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    • pp.104-104
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    • 2001
  • Purpose: In this study, we investigated the possible motor pathways of hemiplegic stroke patients usin combined TMS and BOLD fMRI approach and evaluated the correlation between TMS a fMRI methods. Method: Four subjects, who demonstrated left hemiplegia after stroke, are included. TMS was performed using a Dantec Mag2 stimulator (Dantec Company, USA) in single puls mode with figure eight-shaped coil. Following TMS localization, The BOLD T2*-weight images were acquired with echo planar imaging sequence (TR = 1.2 sec, TE = 60 msec, and flip angle = 90). Motor activation was studied by means of a repetitive fing flexion-extension task. The stimulation protocol comprised 10 cycles of alternating activati and rest (10 images per cycle). Total 60 cycles were performed and each cycle take abou 1.5 sec. The resulting images were then analyzed with STIMULATE (CMRR, U, o Minnesota) to generate functional maps using a student t-test (p < 0.0005) and cluste analysis.

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Caloric restriction and its mimetics

  • Lee, Shin-Hae;Min, Kyung-Jin
    • BMB Reports
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    • 제46권4호
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    • pp.181-187
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    • 2013
  • Caloric restriction is the most reliable intervention to prevent age-related disorders and extend lifespan. The reduction of calories by 10-30% compared to an ad libitum diet is known to extend the longevity of various species from yeast to rodents. The underlying mechanisms by which the benefits of caloric restriction occur have not yet been clearly defined. However, many studies are being conducted in an attempt to elucidate these mechanisms, and there are indications that the benefits of caloric restriction are related to alteration of the metabolic rate and the accumulation of reactive oxygen species. During molecular signaling, insulin/insulin-like growth factor signaling, target of rapamycin pathway, adenosine monophosphate activated protein kinase signaling, and Sirtuin are focused as underlying pathways that mediate the benefits of caloric restriction. Here, we will review the current status of caloric restriction.

Efficient One-Step Synthesis of 2-Arylfurans by Ceric Ammonium Nitrate (CAN)-Mediated Cycloaddition of 1,3-Dicarbonyl Compounds to Alkynes

  • 이용록;변명환;김병소
    • Bulletin of the Korean Chemical Society
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    • 제19권10호
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    • pp.1080-1083
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    • 1998
  • An efficient method for construction of 2-arylfiirans has been developed by ceric(IV) ammonium nitratemediated oxidative cycloaddition of cyclic and acyclic 1,3-dicarbonyl compounds to several alkynes. Reactions of 1,3-cyclohexanedione, 1,3-cyclopentanedione, and 2,4-pentanedione with several alkynes furnish 2-arylfurans in 26-75% yields. Extension of this technology to more complex 4-hydroxy-2-quinolone and 3-hydroxy-lH-phenalen-l-one with phenylacetylene also affords furoquinolinone and ftirophenalenone derivative in moderate yields. Reaction of 4-hydroxycoumarins with phenylacetylene give linear and angular furocoumarin derivatives as a mixture of regioisomer in good yields. The mechanistic pathway for the formation of 2-arylfurans has been also described.

Oroxylin A Induces BDNF Expression on Cortical Neurons through Adenosine A2A Receptor Stimulation: A Possible Role in Neuroprotection

  • Jeon, Se-Jin;Bak, Hae-Rang;Seo, Jung-Eun;Han, So-Min;Lee, Sung-Hoon;Han, Seol-Heui;Kwon, Kyoung-Ja;Ryu, Jong-Hoon;Cheong, Jae-Hoon;Ko, Kwang-Ho;Yang, Sung-Il;Choi, Ji-Woong;Park, Seung-Hwa;Shin, Chan-Young
    • Biomolecules & Therapeutics
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    • 제20권1호
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    • pp.27-35
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    • 2012
  • Oroxylin A is a flavone isolated from a medicinal herb reported to be effective in reducing the inflammatory and oxidative stresses. It also modulates the production of brain derived neurotrophic factor (BDNF) in cortical neurons by the transactivation of cAMP response element-binding protein (CREB). As a neurotrophin, BDNF plays roles in neuronal development, differentiation, synaptogenesis, and neural protection from the harmful stimuli. Adenosine $A2_A$ receptor colocalized with BDNF in brain and the functional interaction between $A2_A$ receptor stimulation and BDNF action has been suggested. In this study, we investigated the possibility that oroxylin A modulates BDNF production in cortical neuron through the regulation of $A2_A$ receptor system. As expected, CGS21680 ($A2_A$ receptor agonist) induced BDNF expression and release, however, an antagonist, ZM241385, prevented oroxylin A-induced increase in BDNF production. Oroxylin A activated the PI3K-Akt-GSK-$3{\beta}$ signaling pathway, which is inhibited by ZM241385 and the blockade of the signaling pathway abolished the increase in BDNF production. The physiological roles of oroxylin A-induced BDNF production were demonstrated by the increased neurite extension as well as synapse formation from neurons. Overall, oroxylin A might regulate BDNF production in cortical neuron through $A2_A$ receptor stimulation, which promotes cellular survival, synapse formation and neurite extension.

근위축 마우스 모델에서 한국산 겨우살이 추출물에 의한 단백질 합성 신호전달 경로의 활성화 (Activation of Signaling Pathways for Protein Synthesis by Korean Mistletoe (Viscum album coloratum) Extract in a Mouse Model of Muscle Atrophy)

  • 정주성;박춘호;김인보;김종배
    • 한국식품영양학회지
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    • 제30권2호
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    • pp.371-377
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    • 2017
  • Muscle atrophy is characterized by a decrease in the mass of the muscle. With an increase in life expectancy and chronic illnesses, the incidence of muscle atrophy is increasing and the quality of life of patients is decreasing. Thus, reducing muscle atrophy is of high clinical and socio-economic importance. Mistletoe is a semi-parasitic plant that has been used as a traditional medicine in many countries to treat various human illnesses. It has been reported that Korean mistletoe extract (KME) has diverse biological functions including anti-tumor, anti-oxidant, anti-diabetic, anti-obesity properties, and extension of lifespan. Especially, we have recently reported that KME improves exercise endurance in mice, indicating its beneficial roles in enhancing the capacity of skeletal muscle. In this study, we investigated whether KME could activate the signaling pathway related to protein synthesis in a mouse model of muscle atrophy. Interestingly, KME efficiently activated the Akt/mTOR pathway, and Akt and mTOR are important signaling hub molecules for the acceleration of protein synthesis in muscle cells. In addition, KME also increased the activity of S6 kinase which is involved in the regulation of muscle cell size. Moreover, the ERK activity, required for transcription of ribosomal RNA for protein synthesis, was also enhanced in KME-treated mouse muscle. These data support the idea that KME increases muscle mass via increased protein synthesis. Our findings also suggest that Korean mistletoe might be a promising candidate for the development of functional foods that are beneficial for preventing muscle atrophy.

Adaptive V1-MT model for motion perception

  • Li, Shuai;Fan, Xiaoguang;Xu, Yuelei;Huang, Jinke
    • KSII Transactions on Internet and Information Systems (TIIS)
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    • 제13권1호
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    • pp.371-384
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    • 2019
  • Motion perception has been tremendously improved in neuroscience and computer vision. The baseline motion perception model is mediated by the dorsal visual pathway involving the cortex areas the primary visual cortex (V1) and the middle temporal (V5 or MT) visual area. However, few works have been done on the extension of neural models to improve the efficacy and robustness of motion perception of real sequences. To overcome shortcomings in situations, such as varying illumination and large displacement, an adaptive V1-MT motion perception (Ad-V1MTMP) algorithm enriched to deal with real sequences is proposed and analyzed. First, the total variation semi-norm model based on Gabor functions (TV-Gabor) for structure-texture decomposition is performed to manage the illumination and color changes. And then, we study the impact of image local context, which is processed in extra-striate visual areas II (V2), on spatial motion integration by MT neurons, and propose a V1-V2 method to extract the image contrast information at a given location. Furthermore, we take feedback inputs from V2 into account during the polling stage. To use the algorithm on natural scenes, finally, multi-scale approach has been used to handle the frequency range, and adaptive pyramidal decomposition and decomposed spatio-temporal filters have been used to diminish computational cost. Theoretical analysis and experimental results suggest the new Ad-V1MTMP algorithm which mimics human primary motion pathway has universal, effective and robust performance.

RAW 264.7 대식세포에서 연자육 추출물(Nelumbo nucifera Gaertner Seed Extract, NSE)의 면역 증강 효과 (The immune enhancement effect of Nelumbo nucifera Gaertner Seed Extract (NSE) in murine macrophage RAW 264.7 cells)

  • 김세정;김산;장세현;윤성란;소보람;박정민;류정아;정성근
    • Journal of Applied Biological Chemistry
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    • 제66권
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    • pp.23-28
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    • 2023
  • 코로나바이러스-19로 인한 세계적인 펜데믹 이후 면역력 강화소재에 대한 관심이 급격히 증가하고 있으므로 산업적, 건강적 측면에서 새로운 소재의 개발이 필요하다. 본 연구에서는 연자육 추출물을 소재로 선정하고 RAW 264.7 쥐 대식세포를 이용하여 면역증진 효과를 평가하였다. 연자육 추출물은 RAW 264.7 세포에서 세포 생존력에 독성을 나타내지 않으면서 nitric oxide 및 reactive oxygen species의 생산을 상향 조절하였다. 또한 연자육 추출물은 RAW 264.7 세포에서 inducible nitric oxide synthase 및 cyclooxygenase-2 발현을 크게 증가시켰다. Enzyme-linked immunosorbent assay 결과에서는 연자육 추출물의 처리가 RAW 264.7 세포에서 interleukin 6 및 tumor necrosis factor-α의 생성을 유의미하게 향상시키는 것으로 나타났다. 또한 연자육 추출물이 p65, I kappa B kinase α/β, 및 I kappa B (IκB) α의 인산화를 크게 상향 조절하고, RAW 264.7 세포에서 IκB α의 발현을 하향 조절하였다. 우리의 연구 결과는 연자육 추출물이 Nuclear factor-kappa B 신호전달 경로를 통해 면역력을 향상시킬 수 있는 잠재적인 건강기능식품 소재가 될 수 있음을 나타낸다.