• Title/Summary/Keyword: ERKs

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Black rice extract protected HepG2 cells from oxidative stress-induced cell death via ERK1/2 and Akt activation

  • Yoon, Jaemin;Ham, Hyeonmi;Sung, Jeehye;Kim, Younghwa;Choi, Youngmin;Lee, Jeom-Sig;Jeong, Heon-Sang;Lee, Junsoo;Kim, Daeil
    • Nutrition Research and Practice
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    • v.8 no.2
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    • pp.125-131
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    • 2014
  • BACKGROUND/OBJECTIVES: The objective of this study was to evaluate the protective effect of black rice extract (BRE) on tert-butyl hydroperoxide (TBHP)-induced oxidative injury in HepG2 cells. MATERIALS/METHODS: Methanolic extract from black rice was evaluated for the protective effect on TBHP-induced oxidative injury in HepG2 cells. Several biomarkers that modulate cell survival and death including reactive oxygen species (ROS), caspase-3 activity, and related cellular kinases were determined. RESULTS: TBHP induced cell death and apoptosis by a rapid increase in ROS generation and caspase-3 activity. Moreover, TBHP-induced oxidative stress resulted in a transient ERK1/2 activation and a sustained increase of JNK1/2 activation. While, BRE pretreatment protects the cells against oxidative stress by reducing cell death, caspase-3 activity, and ROS generation and also by preventing ERKs deactivation and the prolonged JNKs activation. Moreover, pretreatment of BRE increased the activation of ERKs and Akt which are pro-survival signal proteins. However, this effect was blunted in the presence of ERKs and Akt inhibitors. CONCLUSIONS: These results suggest that activation of ERKs and Akt pathway might be involved in the cytoprotective effect of BRE against oxidative stress. Our findings provide new insights into the cytoprotective effects and its possible mechanism of black rice against oxidative stress.

PREVENTION OF CANCER BY DIETARY FACTORS: TARGETING MAP KINASE/AP-1 SIGNAL TRANSDUCTION PATHWAYS

  • Dong, Zigang
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.10a
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    • pp.29-30
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    • 2001
  • MAP kinase/ AP-1 signal transduction components are rapidly initiated by many extracellular stimuli, especially environmental carcinogens. We have investigated the role of MAP kinases (Erks, JNKs, and p38 kinases) and AP-1 signal transduction pathways in the process of cell transformation and carcinogenesis. Incubation of Cl 41 cells with tumor promoters such as TPA, EGF, arsenic, or TNF-$\alpha$ led to cell transformation and activation of MAP kinases.(omitted)

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EGF Reverses Multi-drug Resistance via the p-ERK Pathway in HepG2/ADM and SMMC7721/ADM Hepatocellular Carcinoma Models

  • Yan, Feng;Bai, Li-Ping;Gao, Hua;Zhu, Chang-Ming;Lin, Li;Kang, Xiang-Peng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2619-2623
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    • 2014
  • Aim: To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) in hepatocellular carcinoma (HCC) models. Materials and Methods: HCC MDR cell strain HepG2/adriamycin (ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADM between low and high concentration with gradually increasing concentration. Drug sensitivity and reversal of multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzed by flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Western blotting. Results: The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only to ADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADM and SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis and G0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKs and up-regulated expression of BimEL. Conclusions: EGF might enhance the chemosensitivity of HepG2/ADM and SMMC7721/ADM cells via up-regulating p-ERKs and BimEL protein.

Lycopene Inhibits Proliferation, Invasion and Migration of Human Breast Cancer Cells

  • Koh, Min-Soo;Hwang, Jin-Sun;Moon, A-Ree
    • Biomolecules & Therapeutics
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    • v.18 no.1
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    • pp.92-98
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    • 2010
  • Breast cancer has been estimated as one of the most common causes of cancer death among women. The major cause of death from breast cancer is the metastatic spread of the disease from the primary tumor to distant sites in the body. Lycopene is one of the major carotenoids in fruits and vegetables including tomatoes. Epidemiological studies have shown that the dietary intake of lycopene is associated with decreased risk of cancer. Although mounting evidence shows the chemopreventive effect of lycopene, the role of lycopene in the prevention of metastatic potential of breast cancer has not been determined yet. In the present study, we investigated the inhibitory effect of lycopene on invasive and migratory phenotypes of two highly aggressive breast cancer cell lines, H-Ras-transformed MCF10A human breast epithelial cells (H-Ras MCF10A) and MDA-MB-231 human breast cancer cells. Here, we report that lycopene significantly inhibits invasion and migration as well as proliferation of H-Ras MCF10A and MDA-MB-231 cells. This study suggested an in vitro anti-cancer and anti-metastatic potential of lycopene. We also showed that activations of ERKs and Akt were inhibited by lycopene in H-Ras MCF10A cells, suggesting that the ERKs and Akt signaling pathways may be involved in lycopene-induced anti-proliferative and/or anti-invasive/migratory effects in these cells. Taken in conjunction with the fact that breast cancer metastasis is one of the most lethal malignancies in women, our findings may provide useful information for the application of lycopene in establishing strategy to prevent the metastatic breast cancer.

Curcumin Stimulates Proliferation of Spinal Cord Neural Progenitor Cells via a Mitogen-Activated Protein Kinase Signaling Pathway

  • Son, Sihoon;Kim, Kyoung-Tae;Cho, Dae-Chul;Kim, Hye-Jeong;Sung, Joo-Kyung;Bae, Jae-Sung
    • Journal of Korean Neurosurgical Society
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    • v.56 no.1
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    • pp.1-4
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    • 2014
  • Objective : The aims of our study are to evaluate the effect of curcumin on spinal cord neural progenitor cell (SC-NPC) proliferation and to clarify the mechanisms of mitogen-activated protein (MAP) kinase signaling pathways in SC-NPCs. Methods : We established cultures of SC-NPCs, extracted from the spinal cord of Sprague-Dawley rats weighing 250 g to 350 g. We measured proliferation rates of SC-NPCs after curcumin treatment at different dosage. The immuno-blotting method was used to evaluate the MAP kinase signaling protein that contains extracellular signal-regulated kinases (ERKs), p38, c-Jun $NH_2$-terminal kinases (JNKs) and ${\beta}$-actin as the control group. Results : Curcumin has a biphasic effect on SC-NPC proliferation. Lower dosage (0.1, 0.5, $1{\mu}M$) of curcumin increased SC-NPC proliferation. However, higher dosage decreased SC-NPC proliferation. Also, curcumin stimulates proliferation of SC-NPCs via the MAP kinase signaling pathway, especially involving the p-ERK and p-38 protein. The p-ERK protein and p38 protein levels varied depending on curcumin dosage (0.5 and $1{\mu}M$, p<0.05). Conclusion : Curcumin can stimulate proliferation of SC-NPCs via ERKs and the p38 signaling pathway in low concentrations.

Anti-stress Effects of Ethanol Extract of Ziziphus jujuba Against Corticosterone-Induced Apoptosis in PC12 Cells

  • Da Hye Song;Yu Jin Choi
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2022.09a
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    • pp.119-119
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    • 2022
  • The coronavirus disease 2019 (COVID-19) pandemic may be stressful for people. Public health actions, such as social distancing, can make people feel isolated and lonely and can increase stress and anxiety. As a result, there is a growing interest towards various materials to relieve stress. Thus, the present study aimed to investigate the anti-stress effects of ethanol extract of Ziziphus jujuba in PC12 cells treated with corticosterone and its underling mechanisms. Furthermore, the viability of the cells, the apoptosis of the cells, the level of phosphorylation of extracellular signal-regulated kinases (p-ERKs) expression were measured by MTT assay, LDH assay, Hoechst staining assay and western blotting. Our results showed that the extract of Ziziphus jujuba reversed corticosterone-induced damage in PC12 cells, which increased cell viability, decreased LDH release, and attenuated corticosterone-induced apoptosis as compared with the corticosterone-treated group. Therefore, these data suggest that the extract of Ziziphus jujuba could be a good candidate for development as a functional food supplement in the improve the anti-stress effect.

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A Study on the Scope and Determinants of Electronic Collaboration based on IT in Interorganizational Relationships (기업간 거래에서 정보기술을 활용한 전자적 협력의 범위와 선행요인에 관한 연구)

  • Choi, Su-Jeong
    • Journal of Information Technology Applications and Management
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    • v.15 no.4
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    • pp.159-188
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    • 2008
  • This study suggests strategies which can enable to creation of new opportunities of competitive advantages while operating a long lasting and consistent business with major trading partners, based on interorganizational information systems (IOISs) specially established and installed for interorganizational transactions. Nowadays, IOISs based mechanism having been widely expanded as a conventional business infrastructure for the interorganizational transactions and/or exchanges, it is customary difficult to obtain any strongly sound advantage over the competitors who have adopted even the simplest deployment of the IOIS mechanisms. In this connection, this study intends to investigate the interorganizational collaborative activities conducted by under the auspicious of IOISs, focused on the prospect of the exploitation of IOISs rather than the implementation of the IOISs. In this study, we, firstly, suggest the concept of Electronic Collaboration which can be defined by the collaborative activities conducted by IOISs, compared to the ones conducted on off-line. In addition, we suggest the Electronic Collaboration as a multi-dimensional concept, constituted by three sub-constructs, the Electronic Information Sharing (EIS), the Electronic Joint Activity (EJA), and the construction of the Electronic Relational Knowledge Store (ERKS). Secondly, we empirically verify the effects of relational and environmental determinants on the Electronic Collaboration. In this study, the relational determinants relate to the variables created in interorganizational relationship like Trust, Influence, Relational Specific Asset-asset invested for the transaction-, and Continuity of the relationship. On the other hand, the environmental determinants relate to the variables surrounding the relationship which are difficult to control. We consider Product Complexity, Technological Uncertainty, and Market Variability as the domain of the environmental determinants. To test our hypotheses, we conducted both paper-based survey and online-based survey. After refining the data with missing responses, a total of 150 data was used for analysis. The results were as follows : Firstly, it is statistically significant that the Electronic Collaboration is composed of EIS, EJA, and ERKS. In particular, the results imply that the firms are able to accumulate relational knowledge base as well as to exchange information or knowledge, and to conduct joint activities through effort to further expand the Electronic Collaboration. Secondly, we have verified the individual effects of the relational and the environmental determinants on the Electronic Collaboration. Product Complexity has been revealed as the most influential variable affecting the Electronic Collaboration. Next, Interorganizational Trust and Technological Uncertainty, in that order, have been seen to have significant effects on the Electronic Collaboration. In other words, when products or services seem to be difficult to standardize, and the core technologies seem to rapidly change, the need for the Electronic Collaboration increase. In addition, the observation dictates that the interorganizational trust turns out to be a critical variable in building a relationship and in seeking further collaboration. The results, further, illustrate that the environmental determinants are relatively more effective than the relational determinants, which is not consistent with a few prior researches relational determinants emphasized. It is because this study doesn't consider the size of the firm. A few researchers have given an emphasis on the relational determinants like trust and influence, especially from the perspective of small firms in interorganizational relationship. However, in our study, where all the sizes of the firms are contained, electronic collaboration is considerably affected by the environmental determinants.

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MAPK Activation and Cell Viability after $H_2O_2$ Stimulation in Cultured Feline Ileal Smooth Muscle Cells

  • Song, Hyun-Ju;Jeong, Ji-Hoon;Lee, Dong-Kyu;Lee, Tai-Sang;Min, Young-Sil;Sohn, Uy-Dong
    • The Korean Journal of Physiology and Pharmacology
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    • v.8 no.6
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    • pp.339-344
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    • 2004
  • Recent data have shown the importance of oxidative stresses in the pathogenesis of inflammatory bowel disease, crohn's disease and ulcerative colitis. $H_2O_2$, reactive oxygen species (ROS) donor, has been reported to act as a signaling molecule involved in a variety of cellular functions such as apo/ptosis and proliferation. In the present study, we investigated viability of cultured ileal smooth muscle cells (ISMC) after stimulation with $H_2O_2$. Trypan blue method revealed that the cell viability of ISMC treated with 1 mM $H_2O_2$ was not different from that of controls at up to 2 h time point, while treatment of ISMC with 1 mM $H_2O_2$ for 48 h finally induced significant decrease in the cell viability. Therefore, we evaluated whether $H_2O_2$ was capable of ERKs activation in ISMC for the short-term exposure and examined whether tyrosine kinase was involved in the process of ERK activation by $H_2O_2$ in ISMC. We also investigated the effects of $H_2O_2$ on activation of SAPK/JNK and p38 MAP kinase in ISMC. Thus, ISMC were cultured and exposed to $H_2O_2$, and western blot analysis was performed with phosphospecific MAP kinase antibodies. Robust activation of ERK occurred within 30 min of 1 mM $H_2O_2$ treatment. $H_2O_2-induced$ ERK activation was attenuated by a tyrosine kinase inhibitor, genistein, indicating that tyrosine kinase was probably involved in the ERK activation by $H_2O_2$. $H_2O_2$ was a moderate activator of SAPK/JNK, while p38 MAP kinase was not activated by $H_2O_2$. We suggest that ERK activation induced by short-term $H_2O_2$ treatment plays a critical role in cellular protection in the early stage of response to oxidative stress. The present study suggests the necessity of identification of MAPK signaling pathways affected by ROS, since it could ultimately elucidate cellular consequences involved in initiation and perpetuation of intestinal tissue damage in the diseases such as crohn's disease and ulcerative colitis, resulted from excessive ROS.

A Role of Mitogen Activated Protein Kinases and Inflammatory Responses in Gender Differences in Kidney Ischemia Injury

  • Park, Kwon-Moo;Han, Ho-Jae
    • The Korean Journal of Physiology and Pharmacology
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    • v.6 no.3
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    • pp.155-160
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    • 2002
  • It is not known whether gender differences play a role in susceptibility to ischemic acute renal failure. Thus, we examined if there were any differences in susceptibility between male and female mice to kidney ischemic injury, and if so, whether it is due to differences in mitogen activated protein kinases (MAPKs) or inflammatory responses to ischemia. Female mice were protected against kidney ischemia when compared with males. Thirty minutes of bilateral ischemia resulted in marked functional and morphological damages in males, but not in females. The ischemia-induced phosphorylation of c-jun N-terminal stress-activated protein kinases (JNKs) was higher in males than in females. Phosphorylation of extracellular signal-regulated kinases (ERKs) was lower in males than in females. Post- ischemia medullary infiltration of RAW 264.7 cell, a monocyte-macrophage cell, and intercellular adhesion molecule-1 (ICAM-1) were greater in males than in females. In conclusion, males were much more susceptible to ischemia than females. The enhanced propensity to ischemic injury in males was correlated with greater activation of JNKs, greater expression of ICAM-1, and greater trapping of leukocytes in the medulla.

Role of Exogenous Nitric Oxide Generated through Microwave Plasma Activate the Oxidative Signaling Components in Differentiation of Myoblast cells into Myotube

  • Kumar, Naresh;Shaw, Priyanka;Attri, Pankaj;Uhm, Han Sup;Choi, Eun Ha
    • Proceedings of the Korean Vacuum Society Conference
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    • 2015.08a
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    • pp.158-158
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    • 2015
  • Myoblast are myogenic precursors that proliferate, activate, and differentiate on muscle injury to sustain the regenerative capacity of skeletal muscle; The neuronal isoform of nitric oxide synthase (nNOS, termed also NOS-I) is expressed in normal adult skeletal muscle, suggesting important functions for Nitric oxide (NO) in muscle biology1,2,3. However, the expression and subcellular localization of NO in muscle development and myoblast differentiation are largely unknown. In this study, we examined effects of the nitric oxide generated by a microwave plasma torch, on proliferation/differentiation of rat myoblastic L6 cells. Experimental data pertaining to nitric oxide production are presented in terms of the oxygen input in units of cubic centimetres per minute. The various levels of nitric oxide are observed depending on the flow rate of nitrogen gas, the ratio of oxygen gas, and the microwave power4. In order to evaluate the potential of nitric oxide as an activator of cell differentiation, we applied nitric oxide generated from the microwave plasma torch to L6 skeletal muscles. Differentiation of L6 cells into myotubes was significantly enhanced the differentiation after nitric oxide treatment. Nitric oxide treatment also increase the expression of myogenesis marker proteins and mRNA level, such as myogenin and myosin heavy chain (MHC), as well as cyclic guanosine monophosphate (cGMP), However during the myotube differentiation we found that NO activate oxidative stress signaling erks expression. Therefore, these results establish a role of NO and cGMP in regulating myoblast differentiation and elucidate their mechanism of action, providing a direct link with oxidative stress signalling, which is a key player in myogenesis. Based on these findings, nitric oxide generated by plasma can be used as a possible activator of cell differentiation and tissue regeneration.

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