• 제목/요약/키워드: selective activation

검색결과 348건 처리시간 0.026초

A Correlative Study on Amyloid β-Induced Cell Death Independent of Caspase Activation

  • Tuyet, Pham Thi Dieu
    • Journal of Integrative Natural Science
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    • 제7권2호
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    • pp.87-91
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    • 2014
  • Amyloid beta ($A{\beta}$) peptide has been implicated in the pathogenesis of Alzheimer's disease and has been reported to induce apoptotic death in cell culture. Cysteine Proteases, a family of enzymes known as caspases, mediate cell death in many models of apoptosis. In the present study, we examined the caspase activity and cell death in $A{\beta}$-treated SHSY5Y cells, as an attempt to elucidate the relationship between the type of caspase and $A{\beta}$-induced cell death. $A{\beta}$ at 20 ${\mu}M$ induce activation of caspase-3, 8 and 9 activity, but not the caspase-1. Caspase-3, 8 and 9 were processed by Ab treatment, consistent with the activity assay. Inhibition of the caspase activities by the selective inhibitors, however, marginally affected the cell death induced by $A{\beta}$. Taken together, the results indicate that $A{\beta}$-induced cell death may be independent of caspase activity and rather, the enzymes might be activated as a result of the cell death.

Transient receptor potential melastatin type 7 channels are involved in zinc-induced apoptosis in gastric cancer

  • Kim, Byung-Joo
    • Animal cells and systems
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    • 제15권2호
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    • pp.123-130
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    • 2011
  • Transient receptor potential melastatin 7 (TRPM7) channels are novel $Ca^{2+}$-permeable non-selective cation channels that are ubiquitously expressed. Activation of TRPM7 channels has been shown to be involved in the survival of gastric cancer cells. Here we show evidence suggesting that TRPM7 channels play an important role in $Zn^{2+}$- mediated cellular injury. Using a combination of electrophysiology, pharmacological analysis, small interfering RNA (siRNA) methods and cell death assays, we showed that activation of TRPM7 channels augmented $Zn^{2+}$-induced apoptosis of AGS cells, the most common human gastric adenocarcinoma cell line. The $Zn^{2+}$-mediated cytotoxicity was inhibited by the non-specific TRPM7 blockers $Gd^{3+}$ or 2 aminoethoxydiphenyl borate (2-APB) and TRPM7 specific siRNA. In addition, we showed that overexpression of TRPM7 channels in HEK293 cells increased $Zn^{2+}$- induced cell injury. Thus, TRPM7 channels may represent a novel target for physiological disorders where $Zn^{2+}$ toxicity plays an important role.

Natural Killer Cell and Cancer Immunotherapy (자연살해세포와 항암면역치료)

  • Kim, Hun Sik
    • Hanyang Medical Reviews
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    • 제33권1호
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    • pp.59-64
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    • 2013
  • Cancer remains the leading cause of death worldwide despite intense efforts in developing innovative treatments. Current approaches in cancer therapy are mainly directed to a selective targeting of cancer cells to avoid potential side effects associated with conventional therapy. In this respect, Natural killer (NK) cells have gained growing attention and are now being considered as promising therapeutic tools for cancer therapy owing to their intrinsic ability to rapidly recognize and kill cancer cells, while sparing normal healthy cells. NK cells play a key role in the first line of defense against transformed and virus-infected cells. NK cells sense their target through a whole array of receptors, both activating and inhibitory. Functional outcome of NK cell against target cells is determined by the balance of signals transmitted from diverse activating and inhibiting receptors. Despite significant progress made in the role of NK cells attack as a pivotal sentinel in tumor surveillance, the molecular has been that regulate NK cell responses remain unclear, which restricts the use of NK cells as a therapeutic measure. Accordingly, current efforts for NK cell-based cancer therapy have largely relied on the strategies that are based on the manipulation of inhibitory receptor function. However, if we better understand the mechanisms governing NK cell activation, including those mediated by diverse activating receptors, this knowledge can be applied to the development of optimal design for cancer immunotherapy by targeting NK cells.

Comparison Among Shoulder Diagonal Pattern of Exercises Considering Phase of Contraction Based on Muscle Activity (상지의 대각선 운동형태와 수축형태에 따른 근활성도 비교연구)

  • Soo-Han Kim;Se-Yeon Park
    • PNF and Movement
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    • 제22권1호
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    • pp.151-158
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    • 2024
  • Purpose: The present study investigated how variations in diagonal exercises affect shoulder muscle activity, examining changes in neuromuscular activation during scapular and shoulder diagonal patterns of exercises. Furthermore, we explored whether the exercise phase affects muscle activation. Methods: Sixteen asymptomatic male participants were recruited. Four diagonal pattern exercises (scapular anterior elevation, posterior elevation, flexion-adduction-external rotation, flexion, abduction-external rotation), and two exercise phases (concentric and eccentric) were administered. Surface electromyography data were collected. Results: Upper trapezius activity was significantly higher during the concentric phase of scapular posterior elevation exercises compared with the others (p<0.05). The serratus anterior, anterior deltoid, and infraspinatus activities were significantly higher during shoulder diagonal pattern exercises compared with the scapular diagonal pattern exercises (p<0.05). Except for the lower trapezius, muscular activities during the concentric phase were significantly greater compared with the eccentric phase (p<0.05). Conclusion: The current study suggests that the diagonal pattern of exercise may contribute to selective strengthening of the shoulder complex muscles and that the form of exercise should be tailored to the subject. It also suggests that diagonal exercises with concentric contractions tend to be more beneficial than eccentric contractions for overall muscle recruitment, but the effects vary for specific diagonal patterns.

The Adsorption Characteristics by the Optimun Activation Process of PAN-based Carbon Fiber and SO2 Adsorption Characteristics by the Impregnated Nanoparticles (PAN계 ACF의 최적 활성화 공정에 따른 흡착특성과 나노입자 첨착에 의한 SO2 흡착특성)

  • Lee, Jin-Jae;Kim, Young-Chai
    • Applied Chemistry for Engineering
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    • 제17권5호
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    • pp.532-538
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    • 2006
  • The carbonization and activation conditions for the PAN-based ACF of various grade were investigated to obtain the optimun activation condition with high surface area. And the surface properties and the absorption performance of toxic gas for terror were examined toward the PAN-ACF with the highest surface area. In the test results the surface area increased with increase of the activation temperature, but decreased with increase of the carbonization temperature. After carbonization condition ($900^{\circ}C$-15min) and activation condition ($900^{\circ}C$-30 min), we got the ACF with the highest surface area of $1204m^2/g$. In the absorption test of iodine and toxic gas for terror, this ACF showed more excellent absorption performance than the existing carbon-based adsorbent. Also, in order to give the function characteristic for a selective absorption, the stable nanoparticles of the Ag, Pt, Cu, Pd were prepared and impregnated on the PAN-based ACF in replacement of the existing method supporting metal catalysis. And were analyzed the surface characteristics and the $SO_{2}$ adsorption characteristics. In the $SO_{2}$ absorption performance test of the PAN-ACF with the impregnated nanoparticles, it wasn't change breakthrough time of Ag, Pt, Cu nanoparticle supported the PAN-ACF comparing with breakthrough time (326 sec) of the non supported PAN-ACF but Pd nanoparticle supported the PAN-ACF achieved excellent $SO_{2}$ absorption performance which has break-through time 925 sec.

Effect of Glenohumeral Joint Rotation on Serratus Anterior, Pectoralis Major and Upper Trapezius EMG Activity during Push-up Plus Exercise

  • Shim, Young-Hun;Nam, Ki-Seok;Park, Ji-Won
    • The Journal of Korean Physical Therapy
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    • 제28권2호
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    • pp.106-111
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    • 2016
  • Purpose: The aim of this study is to determine the effect of glenohumeral (GH) rotation position in modified knee push-up plus exercise (MKPUP) by examining the surface electromyography (EMG) amplitude in serratus anterior (SA), pectoralis major (PM), and upper trapezius (UTz) and the activity ratio of each muscle. Methods: A total of 22 healthy subjects volunteered for the study. Each subject performed the MKPUP at $0^{\circ}$, $45^{\circ}$, and $90^{\circ}$ of GH joint internal rotation. EMG of the SA and PM, UTz was compared between GH rotation positions and each muscle activity ratio. EMG was used to measure the muscle activity in terms of ratios to maximal voluntary isometric contraction (MVIC). Results: The difference in EMG activity during the exercise in three GH joint internal rotation positions was observed with the SA and the PM. The greater the GH joint internal rotation angle was, the lower the activity of the PM. In contrast, the SA showed higher activity. However, the activity of UT was similar under all conditions. The ratio of the SA and the PM was considerably greater at $90^{\circ}$ GH joint internal rotation than at $0^{\circ}$ and $45^{\circ}$. Conclusion: When excessive activation of the PM or imbalanced activation between the PM and the SA occurs, the MKPUP exercise is most effective at $90^{\circ}$ of GH joint internal rotation. Use of this position would be a beneficial strategy for selective strengthening of the SA and minimizing PM activation.

NMDA Receptor Activation Mediates Neuropathic Pain States Induced by Calcium Channel α2δ1 Subunit (신경병증성 통증과정의 NMDA 수용체 활성과 칼슘통로 α2δ1 Subunit의 영향)

  • Yu, Soo Bong;Lim, Young Soo;Kim, Doo Sik
    • The Korean Journal of Pain
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    • 제22권3호
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    • pp.210-215
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    • 2009
  • Background: Several studies have indicated that a nerve injury enhances the expression of the voltage-gated calcium channel ${\alpha}2{\delta}1$ subunit (Cav ${\alpha}2{\delta}1$) in sensory neurons and the dorsal spinal cord. This study examined whether NMDA receptor activation is essential for Cav ${\alpha}2{\delta}1$-mediated tactile allodynia in Cav ${\alpha}2{\delta}1$ overexpressing transgenic mice and L5/6 spinal nerve ligated rats (SNL). These two models show similar Cav ${\alpha}2{\delta}1$ upregulation and behavioral hypersensitivity, without and with the presence of other injury factors, respectively. Methods: The transgenic (TG) mice were generated as described elsewhere (Feng et al., 2000). The left L5/6 spinal nerves in the Harlan Sprague Dawley rats were ligated tightly (SNL) to induce neuropathic pain, as described by Kim et al. (1992). Memantine 2 mg/kg (10 ul) was injected directly into the L5/6 spinal region followed by $10{\mu}l$ saline. Tactile allodynia was tested for any mechanical hypersensitivity. Results: The tactile allodynia in the SNL rats could be reversed by an intrathecal injection of memantine 2 mg/kg at 1.5 hours. The tactile allodynia in the Cav ${\alpha}2{\delta}1$ over-expressing TG mice could be reversed by an intrathecal injection of memantine 2 mg/kg at 1.5, 2.0 and 2.5 hours. Conclusions: The behavioral hypersensitivity was similar in the TG mice and nerve injury pain model, supporting the hypothesis that elevated Cav ${\alpha}2{\delta}1$ mediates similar pathways that underlie the pain states in both models. The selective activation of spinal NMDA receptors plays a key role in mediating the pain states in both the nerve-injury rats and TG mice.

Cilostazol Inhibits Vascular Smooth Muscle Cell Proliferation and Reactive Oxygen Species Production through Activation of AMP-activated Protein Kinase Induced by Heme Oxygenase-1

  • Kim, Jung-Eun;Sung, Jin-Young;Woo, Chang-Hoon;Kang, Young-Jin;Lee, Kwang-Youn;Kim, Hee-Sun;Kwun, Woo-Hyung;Choi, Hyoung-Chul
    • The Korean Journal of Physiology and Pharmacology
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    • 제15권4호
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    • pp.203-210
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    • 2011
  • Cilostazol is a selective inhibitor of phosphodiesterase 3 that increases intracellular cAMP levels and activates protein kinase A, thereby inhibiting vascular smooth muscle cell (VSMC) proliferation. We investigated whether AMP-activated protein kinase (AMPK) activation induced by heme oxygenase-1 (HO-1) is a mediator of the beneficial effects of cilostazol and whether cilostazol may prevent cell proliferation and reactive oxygen species (ROS) production by activating AMPK in VSMC. In the present study, we investigated VSMC with various concentrations of cilostazol. Treatment with cilostazol increased HO-1 expression and phosphorylation of AMPK in a dose- and time-dependent manner. Cilostazol also significantly decreased platelet-derived growth factor (PDGF)-induced VSMC proliferation and ROS production by activating AMPK induced by HO-1. Pharmacological and genetic inhibition of HO-1 and AMPK blocked the cilostazol-induced inhibition of cell proliferation and ROS production.These data suggest that cilostazol-induced HO-1 expression and AMPK activation might attenuate PDGF-induced VSMC proliferation and ROS production.

Nitric Oxide Prevents the Bovine Cerebral Endothelial Cell Death Induced by Serum-Deprivation

  • Kim, Chul-Hoon;Ahn, Young-Soo
    • The Korean Journal of Physiology and Pharmacology
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    • 제1권5호
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    • pp.515-521
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    • 1997
  • Endothelial cells play a central role in the inflammatory processes, and activation of nuclear factor kappa B ($NF-_{\kappa}B$) is a key component in that inflammatory processes. Previously, we reported that tumor necrosis factor alpha($TNF{\alpha}$) had protective effect of cell death induced by serum deprivation and this protection was related to $NF-_{\kappa}B$ activation. Inducible nitric oxide synthase (iNOS) is a member of the molecules which transcription is regulated mainly by $NF-_{\kappa}B$. And the role of nitric oxide (NO) generated by iNOS on cell viability is still controversial. To elucidate the mechanism of $TNF{\alpha}$ and $NF-_{\kappa}B$ activation on cell death protection, we investigate the effect of NO on the cell death induced by serum- deprivation in bovine cerebral endothelial cells in this study. Addition of $TNF{\alpha}$, which are inducer of iNOS, prevented serum-deprivation induced cell death. Increased expression of iNOS was confirmed indirectly by nitrite measurement. When selective iNOS inhibitors were treated, the protective effect of $TNF{\alpha}$ on cell death was partially blocked, suggesting that iNOS expression was involved in controlling cell death. Exogenously added NO substrate (L-arginine) and NO donors (sodium nitroprusside and S-nitroso-N-acetylpenicillamine) also inhibited the cell death induced by serum deprivation. These results suggest that NO has protective effect on bovine cerebral endothelial cell death induced by serum-deprivation and that iNOS is one of the possible target molecules by which $NF-_{\kappa}B$ exerts its cytoprotective effect.

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TI-I-174, a Synthetic Chalcone Derivative, Suppresses Nitric Oxide Production in Murine Macrophages via Heme Oxygenase-1 Induction and Inhibition of AP-1

  • Kim, Mi Jin;Kadayat, Taraman;Kim, Da Eun;Lee, Eung-Seok;Park, Pil-Hoon
    • Biomolecules & Therapeutics
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    • 제22권5호
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    • pp.390-399
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    • 2014
  • Chalcones (1,3-diaryl-2-propen-1-ones), a flavonoid subfamily, are widely known for their anti-inflammatory properties. Propenone moiety in chalcones is known to play an important role in generating biological responses by chalcones. In the present study, we synthesized chalcone derivatives structurally modified in propenone moiety and examined inhibitory effect on nitric oxide (NO) production and its potential mechanisms. Among the chalcone derivatives used for this study, TI-I-174 (3-(2-Hydroxyphenyl)-1-(thiophen-3-yl)prop-2-en-1-one) most potently inhibited lipopolysaccharide (LPS)-stimulated nitrite production in RAW 264.7 macrophages. TI-I-174 treatment also markedly inhibited inducible nitric oxide synthase (iNOS) expression. However, TI-I-174 did not significantly affect production of IL-6, cyclooxygenase-2 (COX-2) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), implying that TI-I-174 inhibits production of inflammatory mediators in a selective manner. Treatment of macrophages with TI-I-174 significantly inhibited transcriptional activity of activator protein-1 (AP-1) as determined by luciferase reporter gene assay, whereas nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity was not affected by TI-I-1744. In addition, TI-I-174 significantly inhibited activation of c-Jun-N-Terminal kinase (JNK) without affecting ERK1/2 and p38MAPK, indicating that down-regulation of iNOS gene expression by TI-I-174 is mainly attributed by blockade of JNK/AP-1 activation. We also demonstrated that TI-I-174 treatment led to an increase in heme oxygenase-1 (HO-1) expression both at mRNA and protein level. Transfection of siRNA targeting HO-1 reversed TI-I-174-mediated inhibition of nitrite production. Taken together, these results indicate that TI-I-174 suppresses NO production in LPS-stimulated RAW 264.7 macrophages via induction of HO-1 and blockade of AP-1 activation.