• Title/Summary/Keyword: JAK3

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SOCS1 counteracts ROS-mediated survival signals and promotes apoptosis by modulating cell cycle to increase radiosensitivity of colorectal cancer cells

  • Ryu, Ji-Yoon;Oh, Jiyoung;Kim, Su-Min;Kim, Won-Gi;Jeong, Hana;Ahn, Shin-Ae;Kim, Seol-Hee;Jang, Ji-Young;Yoo, Byong Chul;Kim, Chul Woo;Lee, Choong-Eun
    • BMB Reports
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    • v.55 no.4
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    • pp.198-203
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    • 2022
  • As negative regulators of cytokine signaling pathways, suppressors of cytokine signaling (SOCS) proteins have been reported to possess both pro-tumor and anti-tumor functions. Our recent studies have demonstrated suppressive effects of SOCS1 on epithelial to mesenchymal signaling in colorectal cancer cells in response to fractionated ionizing radiation or oxidative stress. The objective of the present study was to determine the radiosensitizing action of SOCS1 as an anti-tumor mechanism in colorectal cancer cell model. In HCT116 cells exposed to ionizing radiation, SOCS1 over-expression shifted cell cycle arrest from G2/M to G1 and promoted radiation-induced apoptosis in a p53-dependent manner with down-regulation of cyclin B and up-regulation of p21. On the other hand, SOCS1 knock-down resulted in a reduced apoptosis with a decrease in G1 arrest. The regulatory action of SOCS1 on the radiation response was mediated by inhibition of radiation-induced Jak3/STAT3 and Erk activities, thereby blocking G1 to S transition. Radiation-induced early ROS signal was responsible for the activation of Jak3/Erk/STAT3 that led to cell survival response. Our data collectively indicate that SOCS1 can promote radiosensitivity of colorectal cancer cells by counteracting ROS-mediated survival signal, thereby blocking cell cycle progression from G1 to S. The resulting increase in G1 arrest with p53 activation then contributes to the promotion of apoptotic response upon radiation. Thus, induction of SOCS1 expression may increase therapeutic efficacy of radiation in tumors with low SOCS1 levels.

Analysis of Polycyclic Aromatic Hydrocarbons in Agricultural Soils by Gas Chromatography-Ion Trap Tandem Mass Spectrometry

  • Nam, Jae-Jak;Lee, Sang-Hak
    • Proceedings of the Korean Environmental Sciences Society Conference
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    • 2003.11a
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    • pp.113-118
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    • 2003
  • An investigation has been carried out on collision-induced dissociation (CID) in the development of an analytical protocol for the determination of polycyclic aromatic hydrocarbons (PARs) by ion trap tandem mass spectrometry. Two different considerations were used to choose the optimal CID conditions for complex matrix environmental samples, namely, to determine the highest signal-to-noise (SIN) ratio and the other to eliminate the background interferences originated from complex matrix samples. The PAR content of agricultural soil was measured to estimate overall distribution of PAR in throughout the country, we collected and analyzed 226 soil samples from paddy and upland soil. The average content of total PAR in all samples was 236 ${\mu}g$ $kg^{-1}$, and the range was from 23.3 to 2, 834 ${\mu}g$ $kg^{-1}$. The overall distribution of PAR was found to be closely related to the pollution sources, the size of city and the type of industry.

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Mechanisms of Type-I Interferon Signal Transduction

  • Uddin, Shahab;Platanias, Leonidas C.
    • BMB Reports
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    • v.37 no.6
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    • pp.635-641
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    • 2004
  • Interferons regulate a number of biological functions including control of cell proliferation, generation of antiviral activities and immumodulation in human cells. Studies by several investigators have identified a number of cellular signaling cascades that are activated during engagement of interferon receptors. The activation of multiple signaling cascades by the interferon receptors appears to be critical for the generation of interferon mediated biological functions and immune surveillance. The present review summarizes the existing knowledge on the multiple signaling cascades activated by Type I interferons. Recent developments in this research area are emphasized and the implications of these new discoveries on our understanding of interferon actions are discussed.

First Record of the Stichaeid Fish Chirolophis saitone (Perciformes: Stichaeidae) from Korea

  • Kim, Maeng Jin;Choi, Jung Hwa;Lee, Dong Woo;Kim, Jung Yun;Choi, Kwang Ho
    • Fisheries and Aquatic Sciences
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    • v.16 no.3
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    • pp.195-197
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    • 2013
  • One specimen of Chirolophis saitone, belonging to the family Stichaeidae, was collected by a bottom trawl in the southern area of the Yellow Sea. The present specimen was characterized by 52 dorsal fin spines, 38 anal fin spines, a caudal fin with four vertical dark bands and an orbital region with three pairs of branched cirri. We propose a new Korean name, "Jak-eun-goe-do-ra-chi', for C. saitone.

Effect of all-trans retinoic acid on casein and fatty acid synthesis in MAC-T cells

  • Liao, Xian-Dong;Zhou, Chang-Hai;Zhang, Jing;Shen, Jing-Lin;Wang, Ya-Jing;Jin, Yong-Cheng;Li, Sheng-Li
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.6
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    • pp.1012-1022
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    • 2020
  • Objective: Caseins and fatty acids of milk are synthesized and secreted by the epithelial cells of the mammary gland. All-trans retinoic acid (ATRA), an active metabolite of vitamin A, has been shown to promote mammary development. This study was conducted to determine the effect of ATRA on casein synthesis and fatty acid composition in MAC-T cells. Methods: MAC-T cells were allowed to differentiate for 4 d, treated with ATRA (0, 1.0, 1.5, and 2.0 μM), and incubated for 3 d. We analyzed the fatty acid composition, the mRNA expression of casein and fatty acid synthesis-related genes, and the phosphorylation of casein synthesis-related proteins of MAC-T cells by gas chromatography, quantitative polymerase chain reaction, and western blotting, respectively. Results: In MAC-T cells, ATRA increased the mRNA levels of αS1-casein and β-casein, janus kinase 2 (JAK2) and E74-like factor 5 of the signal transducer and activator of transcription 5 β (STAT5-β) pathway, ribosomal protein S6 kinase beta-1 (S6K1) and eukaryotic translation initiation factor 4E binding protein 1 of the mammalian target of rapamycin (mTOR) pathway, inhibited the mRNA expression of phosphoinositide 3-kinase and eukaryotic initiation factor 4E of the mTOR pathway, and promoted the phosphorylation of STAT5-β and S6K1 proteins. Additionally, ATRA increased the de novo synthesis of fatty acids, reduced the content of long-chain fatty acids, the ratio of monounsaturated fatty acids to saturated fatty acids (SFA), the ratio of polyunsaturated fatty acids (PUFA) to SFA, and the ratio of ω-6 to ω-3 PUFA. The mRNA levels of acetyl-CoA carboxylase 1, fatty acid synthase, lipoprotein lipase, stearoyl-CoA desaturase, peroxisome proliferator-activated receptor gamma, and sterol regulatory element-binding protein 1 (SREBP1) were enhanced by ATRA. Conclusion: ATRA promotes the synthesis of casein by regulating JAK2/STAT5 pathway and downstream mTOR signaling pathway, and it improves the fatty acid composition of MAC-T cells by regulating SREBP1-related genes.

Anti-cancer Effects and Molecular Mechanisms of Withaferin A (Withaferin A의 다양한 항암 효과 및 분자생화학적 기전)

  • Woo, Seon Min;Min, Kyoung-Jin;Kwon, Taeg Kyu
    • Journal of Life Science
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    • v.23 no.3
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    • pp.462-469
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    • 2013
  • Withaferin A is a steroidal lactone purified from the Indian medicinal plant Withania somnifera. It exhibits a wide variety of activities, including anti-tumor, anti-inflammation, and immunomodulation properties. In this review, we focused on the anti-cancer effects of withaferin A. Withaferin A inhibits cell proliferation, metastasis, invasion, and angiogenesis in cancer cells. Furthermore, it sensitized irradiation, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-, and doxorubicin-mediated apoptosis. The results showed that multiple mechanisms were involved in withaferin A-mediated anti-cancer effects. First, withaferin A increased intracellular reactive oxygen species (ROS) production and induced ER stress- and mitochondria-mediated apoptosis. Second, withaferin A inhibited the signaling pathways (Jak/STAT, Akt, Notch, and c-Met), which are important in cell survival, proliferation, and metastasis. Third, it induced apoptosis and inhibited cancer cell migration through the up-regulation of prostate apoptosis protein-4 (Par-4). Finally, withaferin A up-regulated pro-apoptotic protein expression levels through the inhibition of proteasome activity. Our findings suggested that withaferin A is a potential, potent therapeutic agent.

The origin and development process of laver culture industry in Korea -1. Laver culture history till the end of Chosun dynasty- (우리나라 김양식업의 발상과 발달과정 -1. 조선왕조말엽까지의 김양식사-)

  • BAE Su-Hwan
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.24 no.3
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    • pp.153-166
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    • 1991
  • Laver is sea weeds that might have been eaten by Korean people since ancient times. The begining of laver culture is not known exactly, but it appears to be prehistoric age. Some laver culture complexes have been built in southern coastal sea of Korea around 1910. This paper was considered about the origin and development process of Korean laver culture industry by investigating Korean and Asian old books concerned. The results are as follows. 1. According to the Korean old books ralated, the name of laver is classified into 10kinds. Gim and Hae-I were called by Korean. Gim means weeds and Hae-I means the manufactured laver by cutting and drying like paper sheet. Ja-Chae and Hae-Tae are come from Chinese, however they are commonly called by Korean, Japanese and Chinese. Rest six names are come from Chinese botany. 2. As Chinese used laver as medicine for wen, scrofula, fever, vomiting, diarrhoea and. so on, they didn't regard it as foods and took into account an warning by Chinese botany that they could take ill when overeating it. On the other as Korean people have eaten it with pleasure nevertheless the Chinese warning, various foods using laver have been developed. The typical food is rice covering laver sheet. It is also popular to Japanese. 3. Laver culture can be carried out in all coastal seas around Korean peninsula, the best sea area for it is the middle west of south sea. 4. Seopkkoji type is a laver culture method that when branches of tree are put in tidal flat laver sporules are attached and gronm on them. It was begun by Hae-Jak Kun(a group of fishery slaves) on Kwang-Yang bay the most suitable for. laver growth at the beginning of King $Sung-long(1469{\~}1481)$. It is assumed that when Hae-Jak Kun set Oe-Jeon(a sort of fixing fishing gear) to catch tributary fish for king, they could find grown laver attached on Oe-Jeon and invent Seopkkoji type for exclusive laver culture. That was carried out 200 fears earlier than in Japan. Dde-Bal type is more advanced and productive laver culture method with thinly spilt bamboo tied like screen(one end fixed on bottom and other end set free in water), It is assumed that Dde-Bal type was begun in Wan-Do county in King Chull-Jong(1830). All laver culture methods developed were transfered to Japan.

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Improvement of Leptin Resistance (렙틴 저항성의 개선)

  • Kim, Yong Woon
    • Journal of Yeungnam Medical Science
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    • v.30 no.1
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    • pp.4-9
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    • 2013
  • Leptin, a 16-kDa cytokine, is secreted by adipose tissue in response to the surplus of fat store. Thereby, the brain is informed about the body's energy status. In the hypothalamus, leptin triggers specific neuronal subpopulations (e.g., POMC and NPY neurons) and activates several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway, which eventually translates into decreased food intake and increased energy expenditure. Leptin signal is inhibited by a feedback inhibitory pathway mediated by SOCS3. PTP1B involves another inhibitory pathway of leptin. Leptin potently promotes fat mass loss and body weight reduction in lean subjects. However, it is not widely used in the clinical field because of leptin resistance, which is a common feature of obesity characterized by hyperleptinemia and the failure of exogenous leptin administration to provide therapeutic benefit in rodents and humans. The potential mechanisms of leptin resistance include the following: 1) increases in circulating leptin-binding proteins, 2) reduced transport of leptin across the blood-brain barrier, 3) decreased leptin receptor-B (LRB), and/or 4) the provocation of processes that diminish cellular leptin signaling (inflammation, endoplasmic reticulum stress, feedback inhibition, etc.). Thus, interference of the cellular mechanisms that attenuate leptin signaling improves leptin action in cells and animal models, suggesting the potential utility of these processes as points of therapeutic intervention. Various experimental trials and compounds that improve leptin resistance are introduced in this paper.

Systems Biological Approaches Reveal Non-additive Responses and Multiple Crosstalk Mechanisms between TLR and GPCR Signaling

  • Krishnan, Jayalakshmi;Choi, Sang-Dun
    • Genomics & Informatics
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    • v.10 no.3
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    • pp.153-166
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    • 2012
  • A variety of ligands differ in their capacity to bind the receptor, elicit gene expression, and modulate physiological responses. Such receptors include Toll-like receptors (TLRs), which recognize various patterns of pathogens and lead to primary innate immune activation against invaders, and G-protein coupled receptors (GPCRs), whose interaction with their cognate ligands activates heterotrimeric G proteins and regulates specific downstream effectors, including immuno-stimulating molecules. Once TLRs are activated, they lead to the expression of hundreds of genes together and bridge the arm of innate and adaptive immune responses. We characterized the gene expression profile of Toll-like receptor 4 (TLR4) in RAW 264.7 cells when it bound with its ligand, 2-keto-3-deoxyoctonate (KDO), the active part of lipopolysaccharide. In addition, to determine the network communications among the TLR, Janus kinase (JAK)/signal transducer and activator of transcription (STAT), and GPCR, we tested RAW 264.7 cells with KDO, interferon-${\beta}$, or cAMP analog 8-Br. The ligands were also administered as a pair of double and triple combinations.

Kahweol inhibits lipid accumulation and induces Glucose-uptake through activation of AMP-activated protein kinase (AMPK)

  • Baek, Jung-Hwan;Kim, Nam-Jun;Song, Jun-Kyu;Chun, Kyung-Hee
    • BMB Reports
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    • v.50 no.11
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    • pp.566-571
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    • 2017
  • Weight loss ${\geq}5$ percent is sufficient to significantly reduce health risks for obese people; therefore, development of novel weight loss compounds with reduced toxicity is urgently required. After screening of natural compounds with anti-adipogenesis properties in 3T3-L1 cells, we determined that kahweol, a coffee-specific diterpene, inhibited adipogenesis. Kahweol reduced lipid accumulation and expression levels of adipogenesis and lipid accumulation-related factors. Levels of phosphorylated AKT and phosphorylated JAK2, that induce lipid accumulation, decreased in kahweol-treated cells. Particularly, kahweol treatment significantly increased AMP-activated protein kinase (AMPK) activation. We revealed that depletion of AMPK alleviated reduction in lipid accumulation from kahweol treatment, suggesting that inhibition of lipid accumulation by kahweol is dependent on AMPK activation. We detected more rapid reduction in blood glucose levels in mice administrated kahweol than in control mice. We suggest that kahweol has anti-obesity effects and should be studied further for possible therapeutic applications.