• Title/Summary/Keyword: p38 inhibitor

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Celecoxib inhibits phorbol ester-induced expression of cyclooxygenase-2 and skin-tumor promotion in mouse skin: p38 and AP-1 as possible molecular targets

  • Chun, Kyung-Soo;Park, Kwang-Kyun;Chung, Won-Yoon;Kim, Su-Hyeong;Song, Yong-Sang;Surh, Young-Joon
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.70.1-70.1
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    • 2003
  • Celecoxib, the selective cyclooxygenase-2 (COX-2) inhibitor, has recently been reported to reduce the formation of polyps in patients with familial adenomatous polyposis. This specific COX-2 inhibitor also protects against experimentally induced carcinogenesis, but molecular mechanisms underlying its chemopreventive activities remain largely unresolved. In the present work, we found that celecoxib inhibited 12-O- tetradecanoylphorbol-13-acetate (TPA)-induced expression of COX-2 in female ICR mouse skin when applied topically 30 min prior to TPA as determined by both immunoblot and immunohistochemical analyses. (omitted)

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Expression of $p21^{WAFl/Cip1}$ by $TGF-{\beta}$ Requires ERK Signaling Pathway

  • Kim, Yong-Kee;Bae, Gyu-Un;Cho, Eun-Jung;Lee, Hoi-Young;Lee, Hyang-Won;Han, Jeung-Whan
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.152.2-153
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    • 2003
  • ${\beta}Although$ it has been demonstrated that $p2l^{WAFl/Cip1}$, a well known cell cycle inhibitor, could be induced by $TGF-{\beta}$ in a p53-independent manner, the detailed signal transduction pathways still remain poorly understood. In this study, we show that ERK is required for $TGF-{\beta}$ induction of $p21^{WAF1/Cip1}$, but JNK or p38 MAPK is not. ERK activation by $TGF-{\beta}$ significantly attenuated by treatment with ROS scavenger such as NAC or catalase, indicating that ROS, mainly $H_2O_2$, generation by $TGF-{\beta}$ might stimulate ERK signaling pathway to require the induction of $p21^{WAF1/Cip1}$. (omitted)

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Experimental study on the electrochemical properties of zwitterion and phosphate-based hybrid inhibitors in reinforced concrete (양쪽성 이온 및 인산염 기반 하이브리드 방청제의 전기화학적 특성에 관한 실험적 연구)

  • Tran, Duc Thanh;Jeong, Min-goo;Lee, Han-seung;Yang, Hyun-min;Singh, Jitendra Kumar
    • Proceedings of the Korean Institute of Building Construction Conference
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    • 2022.11a
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    • pp.37-38
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    • 2022
  • During the past decades, the corrosion of the steel rebar embedded in concrete structure surrounding marine environment is actually problematic and required the suitable preventive method. An eco-friendly corrosion inhibitor mix is investigated to stifle the active corrosion in comparison with other commercial corrosion inhibitors. The hybrid inhibitor enhances the corrosion resistance and the workability of concrete. However, it reduces the compressive strength slightly after 28-day-age. The electrochemical studies and mechanical studies are pointed out the corrosion resistance property, corrosion kinetics, and the mechanical properties of all concrete samples. H-3 is the optimum dose of hybrid inhbitor that meets the demand of both electrochemical property and mechanical property. It performs the noble features due to the formation of optimum amount of P-Zwitterions-(Cl)-Fe complex onto the steel rebar surface.

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DEPRENYL INHIBITS POTENTIATED ARSENIC-INDUCED CYTOTOXICITY VIA THE INHIBITION OF C-JUN N- TERMINAL KINASE ACTIVATION

  • Park, Jeong-Weon;Kim, Sang-Geon
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.147-147
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    • 2001
  • A previous study showed that sulfur amino acid deprivation (SAAD) potentiated cytotoxicity induced by arsenic (As) and that activation of ERKl/2, p38 kinase and JNK1 was responsible for the potentiation of As toxicity. In the present study, we found for the first time that deprenyl a selective monoamine oxidase B inhibitor prevented potentiation of As toxicity by SAAD in a dose-dependent manner.(omitted)

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CELECOXIB INHIBITS PHORBOL ESTER-INDUCED PGE$_2$ PRODUCTION AND COX-2 EXPRESSION BY TARGETING OF p38 MAP KINASE AND AP-1 IN MOUSE SKIN

  • Chun, Kyung-Soo;Surh, Young-Joon
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.175-175
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    • 2002
  • Celecoxib, a selective COX-2 inhibitor, has been reported to prevent experimentally induced colon, breast, bladder, and skin carcinogenesis. Moreover, daily intake of celecoxib resulted in significant reduction of polyps in patients with familial adenomatous polyposis.(omitted)

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Hexane Fraction of Melandrium firmum Extract Induces Laminin-332 Expression in Human Keratinocyte (각질형성세포에서 왕불유행 헥산 분획물이 Laminin-332 발현에 미치는 효과)

  • Song, Hye Jin;Kim, Mi-Sun;Lee, Hong Gu;Jin, Mu Hyun;Lee, Sang Hwa
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.2
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    • pp.173-181
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    • 2016
  • Skin basement membrane (BM) is a specialized structure that binds dermis and epidermis of the skin and plays an important role in maintaining skin structure. Structural change and destruction of BM is reported to appear due to UV exposure and aging, which may contribute to skin aging including wrinkle formation and a decrease in elasticity of the skin. One of the key components of the BM is laminin-332 (LN-332), and is a major contributor to epidermal-dermal attachment. In this study, we elucidated the effects of Meladrium firmum hexane fraction (MFHF) on LN-332 expression in HaCaT, a human keratinocyte cell line. Quantitative real-time PCR (RT-PCR) and immunoblot analysis revealed that MFHF induced upregulation of LN-332 gene and protein expression. Next, cells were treated with p38 MAPK inhibitor (SB202190) prior to MFHF treatment to analyze the signaling pathway contributing to LN-332 expression. The mRNA and protein levels of LN-332 expression were suppressed completely by pretreatment with p38 MAPK inhibitor. Furthermore, MFHF also increased the mRNA level of collagen type VII and integrin ${\alpha}6$ of skin BM component. These results collectively suggest that MFHF may have potential as an effective agent to stimulate the synthesis of BM components, and could be used to improve phenomenon of skin aging ascribed to the structural and functional impairments of BM in aged human skin.

Manufacture and Characteristics of Food Additives, Phellineus linteus Powder-containing Anti-obesity Lipase Inhibitor (항비만성 Lipase 저해물질을 함유한 식품첨가용 상황버섯 분말의 제조 및 특성)

  • Lee, Jong-Kug;Jang, Jeong-Hoon;Seo, Geon-Sik;Lee, Jong-Soo
    • The Korean Journal of Mycology
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    • v.38 no.1
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    • pp.54-56
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    • 2010
  • This study was performed to develop anti-obesity Phellineus linteus powder for application as food additives. P. linteus powders which contained anti-obesity lipase inhibitor were prepared by freeze drying and spray drying. Effects of various additives on the quality of their powders were investigated. 10% over addition of dextrin and gum-arabia was good in the rheological properties of their powders and optimal spray temperature was near $130^{\circ}C$. When their powders were sealed and storaged at room temperature for 6 months, its characteristics were not changed. Especially, changes of its colors was repressed by addition of 0.3 M oxalic acid, citric acid and ascorbic acid than those by non-treatment.

Pan-Caspase Inhibitor zVAD Induces Necroptotic and Autophagic Cell Death in TLR3/4-Stimulated Macrophages

  • Chen, Yuan-Shen;Chuang, Wei-Chu;Kung, Hsiu-Ni;Cheng, Ching-Yuan;Huang, Duen-Yi;Sekar, Ponarulselvam;Lin, Wan-Wan
    • Molecules and Cells
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    • v.45 no.4
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    • pp.257-272
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    • 2022
  • In addition to inducing apoptosis, caspase inhibition contributes to necroptosis and/or autophagy depending on the cell type and cellular context. In macrophages, necroptosis can be induced by co-treatment with Toll-like receptor (TLR) ligands (lipopolysaccharide [LPS] for TLR4 and polyinosinic-polycytidylic acid [poly I:C] for TLR3) and a cell-permeable pan-caspase inhibitor zVAD. Here, we elucidated the signaling pathways and molecular mechanisms of cell death. We showed that LPS/zVAD- and poly I:C/zVAD-induced cell death in bone marrow-derived macrophages (BMDMs) was inhibited by receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 and autophagy inhibitor 3-methyladenine. Electron microscopic images displayed autophagosome/autolysosomes, and immunoblotting data revealed increased LC3II expression. Although zVAD did not affect LPS- or poly I:C-induced activation of IKK, JNK, and p38, it enhanced IRF3 and STAT1 activation as well as type I interferon (IFN) expression. In addition, zVAD inhibited ERK and Akt phosphorylation induced by LPS and poly I:C. Of note, zVAD-induced enhancement of the IRF3/IFN/STAT1 axis was abolished by necrostatin-1, while zVAD-induced inhibition of ERK and Akt was not. Our data further support the involvement of autocrine IFNs action in reactive oxygen species (ROS)-dependent necroptosis, LPS/zVAD-elicited ROS production was inhibited by necrostatin-1, neutralizing antibody of IFN receptor (IFNR) and JAK inhibitor AZD1480. Accordingly, both cell death and ROS production induced by TLR ligands plus zVAD were abrogated in STAT1 knockout macrophages. We conclude that enhanced TRIF-RIP1-dependent autocrine action of IFNβ, rather than inhibition of ERK or Akt, is involved in TLRs/zVAD-induced autophagic and necroptotic cell death via the JAK/STAT1/ROS pathway.

Phenolic acids in Panax ginseng inhibit melanin production through bidirectional regulation of melanin synthase transcription via different signaling pathways

  • Jianzeng Liu ;Xiaohao Xu ;Jingyuan Zhou;Guang Sun ;Zhenzhuo Li;Lu Zhai ;Jing Wang ;Rui Ma ;Daqing Zhao;Rui Jiang ;Liwei Sun
    • Journal of Ginseng Research
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    • v.47 no.6
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    • pp.714-725
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    • 2023
  • Background: Our previous investigation indicated that the preparation of Panax ginseng Meyer (P. ginseng) inhibited melanogenesis. It comprised salicylic acid (SA), protocatechuic acid (PA), p-coumaric acid (p-CA), vanillic acid (VA), and caffeic acid (CA). In this investigation, the regulatory effects of P. ginseng phenolic acid monomers on melanin production were assessed. Methods: In vitro and in vivo impact of phenolic acid monomers were assessed. Results: SA, PA, p-CA and VA inhibited tyrosinase (TYR) to reduce melanin production, whereas CA had the opposite effects. SA, PA, p-CA and VA significantly downregulated the melanocortin 1 receptor (MC1R), cycle AMP (cAMP), protein kinase A (PKA), cycle AMP-response element-binding protein (CREB), microphthalmia-associated transcription factor (MITF) pathway, reducing mRNA and protein levels of TYR, tyrosinase-related protein 1 (TYRP1), and TYRP2. Moreover, CA treatment enhanced the cAMP, PKA, and CREB pathways to promote MITF mRNA level and phosphorylation. It also alleviated MITF protein level in α-MSH-stimulated B16F10 cells, comparable to untreated B16F10, increasing the expression of phosphorylation glycogen synthase kinase 3β (p-GSK3β), β-catenin, p-ERK/ERK, and p-p38/p38. Furthermore, the GSK3β inhibitor promoted p-GSK3β and p-MITF expression, as observed in CA-treated cells. Moreover, p38 and ERK inhibitors inhibited CA-stimulated p-p38/p38, p-ERK/ERK, and p-MITF increase, which had negative binding energies with MC1R, as depicted by molecular docking. Conclusion: P. ginseng roots' phenolic acid monomers can safely inhibit melanin production by bidirectionally regulating melanin synthase transcription. Furthermore, they reduced MITF expression via MC1R/cAMP/PKA signaling pathway and enhanced MITF post-translational modification via Wnt/mitogen-activated protein kinase signaling pathway.

The Effect of Sodium Chloride on the Serine-type Fibrinolytic Enzymes and the Thermostability of Extracellular Protease from Bacillus amyloliquefaciens DJ-4

  • Choi, Nack-Shick;Kim, Seung-Ho
    • BMB Reports
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    • v.34 no.2
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    • pp.134-138
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    • 2001
  • By adding sodium chloride (2.5%) into a Bacillus amyloliquefaciens DJ-4 culture broth, two serine-type fibrinolytic proteases with a molecular weight of 29 (subtilisin DJ-4) and 38-kDa were stimulated on the SDS-fibrin zymogram or inhibitor gels. B. amyloliquefaciens DJ-4 showed the highest proteolytic activity (5.52 plasmin NIH unit/ml) on the fibrin plate based on the molar ratio when cells were subjected to the 2.5% NaCl. Using a fibrin plate, the secreted protease from this strain in the presence of 5% NaCl showed that about 49% of the enzyme's activity remained after incubation at $60^{\circ}C$ for 30 min, but as the salt concentration was increased (10% NaCl) the activity nearly disappeared (0.14 plasmin NIH unit/ml). However, through a fibrin zymography assay, three fibrinolytic enzymes (38, 53 and 80-kDa) from the cells in the presence of 10% NaCl were detected. Also, two salt-activated serine-type fibrinolytic professes (29 and 38kDa) showed thermostability from 65 to $70^{\circ}C$ for 30 min. Furthermore, these professes also showed stability, pH 6-11. In particular, 29-kDa (subtilisin DJ-4) was very stable in the pH range of 4-11 at $4^{\circ}C$ for 48 h.

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