7 results on '"Kim, Shin"'
Search Results
2. Dexamethasone Inhibits TRAIL-Induced Apoptosis through c-FLIP(L) Upregulation and DR5 Downregulation by GSK3β Activation in Cancer Cells.
- Author
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Jeon, Mi-Yeon, Woo, Seon Min, Seo, Seung Un, Kim, Sang Hyun, Nam, Ju-Ock, Kim, Shin, Park, Jong-Wook, Kubatka, Peter, Min, Kyoung-jin, and Kwon, Taeg Kyu
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ANTINEOPLASTIC agents ,APOPTOSIS ,CELL lines ,CELL receptors ,CELLULAR signal transduction ,GENE expression ,PROTEIN kinases ,TUMOR necrosis factors ,TUMORS ,TREATMENT effectiveness ,DEXAMETHASONE ,SIGNAL peptides ,PHARMACODYNAMICS - Abstract
Simple Summary: Dexamethasone (DEX) is commonly used as immunosuppressive and chemotherapeutic agent. The effects of DEX on cell death is different, depending on cell types and stimuli. Here, we found that DEX inhibited tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell death in cancer cells. Upregulation of c-FLIP(L) and downregulation of death receptor 5 (DR5) play a critical role in anti-apoptotic effects of DEX in TRAIL-induced apoptosis. DEX upregulated c-FLIP(L) expression at the transcriptional levels through the GSK-3β signaling pathway. Furthermore, DEX also modulated protein stability of DR5 via the GSK-3β/Cbl axis-mediated ubiquitin–proteasome system. Therefore, DEX-induced GSK3β activation plays a critical role in the modulation of c-FLIP(L) and DR5. This finding suggests that DEX reduced effects of anti-cancer drugs in cancer cells. Dexamethasone (DEX), a synthetic glucocorticoid, is commonly used as immunosuppressive and chemotherapeutic agent. This study was undertaken to investigate the effects of DEX on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in cancer cells. We found that upregulation of c-FLIP(L) and downregulation of death receptor 5 (DR5; receptor for TRAIL ligand) contribute to the anti-apoptotic effect of DEX on TRAIL-induced apoptosis. DEX increased c-FLIP(L) expression at the transcriptional levels through the GSK-3β signaling pathway. The pharmacological inhibitor and catalytic mutant of GSK-3β suppressed DEX-induced upregulation of c-FLIP(L) expression. Furthermore, GSK-3β specific inhibitor markedly abolished DEX-mediated reduction of TRAIL-induced apoptosis in human renal cancer cells (Caki-1 and A498), human lung cancer cells (A549), and human breast cancer cells (MDA-MB361). In addition, DEX decreased protein stability of DR5 via GSK-3β-mediated upregulation of Cbl, an E3 ligase of DR5. Knockdown of Cbl by siRNA markedly inhibited DEX-induced DR5 downregulation. Taken together, these results suggest that DEX inhibits TRAIL-mediated apoptosis via GSK-3β-mediated DR5 downregulation and c-FLIP(L) upregulation in cancer cells. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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3. Eicosapentaenoic Acid (EPA) Modulates Glucose Metabolism by Targeting AMP-Activated Protein Kinase (AMPK) Pathway.
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Kim, Nami, Kang, Mi Sun, Nam, Miso, Kim, Shin Ae, Hwang, Geum-Sook, and Kim, Hyeon Soo
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PROTEIN kinases ,EICOSAPENTAENOIC acid ,MITOGEN-activated protein kinases ,GLUCOSE metabolism ,GLUCOSE transporters ,OMEGA-3 fatty acids ,FISH oils ,MUSCLE proteins - Abstract
EPA, an omega-3 polyunsaturated fatty acid, exerts beneficial effects on human health. However, the molecular mechanisms underlying EPA function are poorly understood. The object was to illuminate molecular mechanism underlying EPA's role. Here,
1 H-NMR-based metabolic analysis showed enhanced branched-chain amino acids (BCAAs) and lactate following EPA treatment in skeletal muscle cells. EPA regulated mitochondrial oxygen consumption rate. Furthermore, EPA induced calcium/calmodulin-dependent protein kinase kinase (CaMKK) through the generation of intracellular calcium. This induced the phosphorylation of AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (p38 MAPK) that led to glucose uptake, and the translocation of glucose transporter type 4 (GLUT4) in muscles. In conclusion, EPA exerts benign effects on glucose through the activation of AMPK-p38 MAPK signaling pathways in skeletal muscles. [ABSTRACT FROM AUTHOR]- Published
- 2019
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4. Smad7 and Smad6 bind to discrete regions of Pellino-1 via their MH2 domains to mediate TGF-β1-induced negative regulation of IL-1R/TLR signaling
- Author
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Lee, Youn Sook, Kim, Jun Hwan, Kim, Shin-Tae, Kwon, Jae Young, Hong, Suntaek, Kim, Seong-Jin, and Park, Seok Hee
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TRANSFORMING growth factors-beta , *ANTI-inflammatory agents , *MEMBRANE proteins , *CELLULAR signal transduction , *INTERLEUKIN-1 , *SMALL interfering RNA , *PROTEIN kinases , *GENE expression - Abstract
Abstract: Transforming growth factor-β1 (TGF-β1) performs diverse cellular functions, including anti-inflammatory activity. The inhibitory Smad (I-Smad) Smad6 was previously shown to play an important role in TGF-β1-induced negative regulation of Interleukin-1/Toll-like receptor (IL-1R/TLR) signaling through binding to Pellino-1, an adaptor protein of interleukin-1 receptor associated kinase 1(IRAK1). However, it is unknown whether Smad7, the other inhibitory Smad, also has a role in regulating IL-1R/TLR signaling. Here, we demonstrate that endogeneous Smad7 and Smad6 simultaneously bind to discrete regions of Pellino-1 upon TGF-β1 treatment, via distinct regions of the Smad MH2 domains. In addition, the Smad7-Pellino-1 interaction abrogated NF-κB activity by blocking formation of the IRAK1-mediated IL-1R/TLR signaling complex, subsequently causing reduced expression of pro-inflammatory genes. Double knock-down of endogenous Smad6 and Smad7 genes by RNA interference further reduced the anti-inflammatory activity of TGF-β1 than when compared with single knock-down of Smad7. These results provide evidence that the I-Smads, Smad6 and Smad7, act as critical mediators for effective TGF-β1-mediated suppression of IL-1R/TLR signaling, by simultaneous binding to discrete regions of Pellino-1. [Copyright &y& Elsevier]
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- 2010
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5. Kalirin, a GEF for Rac1, plays an important role in FSTL-1-mediated glucose uptake in skeletal muscle cells.
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Lee, Hye Jeong, Lee, Jung Ok, Lee, Yong Woo, Kim, Shin Ae, Park, Sun Hwa, and Kim, Hyeon Soo
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SKELETAL muscle , *PROTEIN kinases , *PHOSPHORYLATION , *GUANOSINE triphosphatase , *GUANINE nucleotide exchange factors - Abstract
Follistatin-like 1 (FSTL-1) is a novel myokine; however, little is known about its metabolic role. Here, FSTL-1 stimulated glucose uptake in an AMP-activated protein kinase (AMPK)-dependent manner in L6 rat skeletal muscle cells. FSTL-1 increased intracellular calcium concentration. Calcium/calmodulin-dependent protein kinase kinase (CaMKK) inhibition blocked FSTL-1-induced AMPK phosphorylation and glucose uptake. In addition, FSTL-1 stimulated the phosphorylation of p21-activated kinase 1 (PAK1), a small GTPase Rac1 downstream protein. PAK1 knockdown or inhibition of Rac1 blocked FSTL-1-induced glucose uptake; moreover, kalirin, a Rac1 guanine nucleotide exchange factor (GEF), was induced by FSTL-1. Kalirin knockdown with siRNA blocked FSTL-1-induced PAK1 phosphorylation and glucose uptake. Consistent with the induction of Rac1 GEF kalirin, the GTP-bound form of Rac1 was increased by FSTL-1. FSTL-1 increased the production of glucose transporter type 4 (GLUT4) protein and also stimulated the translocation of GLUT4 to the plasma membrane. Translocation of GLUT4 was not observed in cells pre-treated with AMPK inhibitor, Rac1 inhibitor, or kalirin siRNA. In primary myoblast cell culture, FSTL-1 increased glucose uptake in an AMPK-dependent manner. A CaMKK inhibitor or kalirin knockdown blocked FSTL-1-induced glucose uptake. These results suggest that kalirin and Rac1 GEF play important roles in FSTL-1-mediated glucose regulation in skeletal muscle cells. [ABSTRACT FROM AUTHOR]
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- 2017
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6. Acupuncture-mediated inhibition of inflammation facilitates significant functional recovery after spinal cord injury
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Choi, Doo C., Lee, Jee Y., Moon, Youn J., Kim, Shin W., Oh, Tae H., and Yune, Tae Y.
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ACUPUNCTURE , *THERAPEUTICS , *SPINAL cord injuries , *INFLAMMATORY mediators , *NEURONS , *CELL death , *PROTEIN kinases , *MICROGLIA , *APOPTOSIS , *METALLOPROTEINASES - Abstract
Abstract: Here, we first demonstrated the neuroprotective effect of acupuncture after SCI. Acupuncture applied at two specific acupoints, Shuigou (GV26) and Yanglingquan (GB34) significantly alleviated apoptotic cell death of neurons and oligodendrocytes, thereby leading to improved functional recovery after SCI. Acupuncture also inhibited caspase-3 activation and reduced the size of lesion cavity and extent of loss of axons. We also found that the activation of both p38 mitogen-activated protein kinase and resident microglia after injury are significantly attenuated by acupuncture. In addition, acupuncture significantly reduced the expression or activation of pro-nerve growth factor, proinflammatory factors such as tumor necrosis factor-α, interleukin-1β, interleukin-6, nitric oxide synthase, cycloxygenase-2, and matrix metalloprotease-9 after SCI. Thus, our results suggest that the neuroprotection by acupuncture may be partly mediated via inhibition of inflammation and microglial activation after SCI and acupuncture can be used as a potential therapeutic tool for treating acute spinal injury in human. [Copyright &y& Elsevier]
- Published
- 2010
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7. Furosin, an ellagitannin, suppresses RANKL-induced osteoclast differentiation and function through inhibition of MAP kinase activation and actin ring formation
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Park, Eui Kyun, Kim, Myung Sunny, Lee, Seung Ho, Kim, Kyung Hee, Park, Ju-Young, Kim, Tae-Ho, Lee, In-Seon, Woo, Je-Tae, Jung, Jae-Chang, Shin, Hong-In, Choi, Je-Yong, and Kim, Shin-Yoon
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TANNINS , *GALLIC acid , *IMMUNE system , *PROTEIN kinases - Abstract
Abstract: Phenolic compounds including tannins and flavonoids have been implicated in suppression of osteoclast differentiation/function and prevention of bone diseases. However, the effects of hydrolysable tannins on bone metabolism remain to be elucidated. In this study, we found that furosin, a hydrolysable tannin, markedly decreased the differentiation of both murine bone marrow mononuclear cells and Raw264.7 cells into osteoclasts, as revealed by the reduced number of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells and decreased TRAP activity. Furosin appears to target at the early stage of osteoclastic differentiation while having no cytotoxic effect on osteoclast precursors. Analysis of the inhibitory mechanisms of furosin revealed that it inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced activation of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK)/activating protein-1 (AP-1). Furthermore, furosin reduced resorption pit formation in osteoclasts, which was accompanied by disruption of the actin rings. Taken together, these results demonstrate that naturally occurring furosin has an inhibitory activity on both osteoclast differentiation and function through mechanisms involving inhibition of the RANKL-induced p38MAPK and JNK/AP-1 activation as well as actin ring formation. [Copyright &y& Elsevier]
- Published
- 2004
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