• Title/Summary/Keyword: Cellular IP

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Ginseng Gintonin Activates the Human Cardiac Delayed Rectifier K+ Channel: Involvement of Ca2+/Calmodulin Binding Sites

  • Choi, Sun-Hye;Lee, Byung-Hwan;Kim, Hyeon-Joong;Jung, Seok-Won;Kim, Hyun-Sook;Shin, Ho-Chul;Lee, Jun-Hee;Kim, Hyoung-Chun;Rhim, Hyewhon;Hwang, Sung-Hee;Ha, Tal Soo;Kim, Hyun-Ji;Cho, Hana;Nah, Seung-Yeol
    • Molecules and Cells
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    • v.37 no.9
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    • pp.656-663
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    • 2014
  • Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits $[Ca^{2+}]_i$ transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier $K^+$ ($I_{Ks}$) channel is a cardiac $K^+$ channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating $I_{Ks}$ channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human $I_{Ks}$ channel activity by expressing human $I_{Ks}$ channels in Xenopus oocytes. We found that gintonin enhances $I_{Ks}$ channel currents in concentration- and voltage-dependent manners. The $EC_{50}$ for the $I_{Ks}$ channel was $0.05{\pm}0.01{\mu}g/ml$. Gintonin-mediated activation 1 of the $I_{Ks}$ channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an $IP_3$ receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the $I_{Ks}$ channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 $[Ca^{2+}]_i$/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on $I_{Ks}$ channel. However, gintonin had no effect on hERG $K^+$ channel activity. These results show that gintonin-mediated enhancement of $I_{Ks}$ channel currents is achieved through binding of the $[Ca^{2+}]_i$/CaM complex to the C terminus of KCNQ1 subunit.

Ventx1.1 as a Direct Repressor of Early Neural Gene zic3 in Xenopus laevis

  • Umair, Zobia;Kumar, Shiv;Kim, Daniel H.;Rafiq, Khezina;Kumar, Vijay;Kim, SungChan;Park, Jae-Bong;Lee, Jae-Yong;Lee, Unjoo;Kim, Jaebong
    • Molecules and Cells
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    • v.41 no.12
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    • pp.1061-1071
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    • 2018
  • From Xenopus embryo studies, the BMP4/Smad1-targeted gene circuit is a key signaling pathway for specifying the cell fate between the ectoderm and neuro-ectoderm as well as the ventral and dorsal mesoderm. In this context, several BMP4/Smad1 target transcriptional factors have been identified as repressors of the neuro-ectoderm. However, none of these direct target transcription factors in this pathway, including GATA1b, Msx1 and Ventx1.1 have yet been proven as direct repressors of early neuro-ectodermal gene expression. In order to demonstrate that Ventx1.1 is a direct repressor of neuro-ectoderm genes, a genome-wide Xenopus ChIP-Seq of Ventx1.1 was performed. In this study, we demonstrated that Ventx1.1 bound to the Ventx1.1 response cis-acting element 1 and 2 (VRE1 and VRE2) on the promoter for zic3, which is a key early neuro-ectoderm gene, and this Ventx1.1 binding led to repression of zic3 transcription. Site-directed mutagenesis of VRE1 and VRE2 within zic3 promoter completely abolished the repression caused by Ventx1.1. In addition, we found both the positive and negative regulation of zic3 promoter activity by FoxD5b and Xcad2, respectively, and that these occur through the VREs and via modulation of Ventx1.1 levels. Taken together, the results demonstrate that the BMP4/Smad1 target gene, Ventx1.1, is a direct repressor of neuro-ectodermal gene zic3 during early Xenopus embryogenesis.

Histone Methylation Regulates Retinoic Acid-induced Hoxc Gene Expression in F9 EC Cells (F9 EC 세포에서 레티노산에 의해 유도되는 Hoxc 유전자의 발현에 히스톤 메틸화가 미치는 영향)

  • Min, Hyehyun;Kim, Myoung Hee
    • Journal of Life Science
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    • v.25 no.6
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    • pp.703-708
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    • 2015
  • Hox genes encode a highly conserved family of homeodomain-containing transcription factors controlling vertebrate pattern formation along the anteroposterior body axis during embryogenesis. Retinoic acid (RA) is a key morphogen in embryogenesis and a critical regulator of both adult and embryonic cellular activity. Specifically, RA regulates Hox gene expression in mouse- or human-derived embryonic carcinoma (EC) cells. Histone modification has been reported to play a pivotal role in the process of RA-induced gene expression and cell differentiation. As histone modification is thought to play an essential role in RA-induced Hox gene expression, we examined RA-induced initiation of collinear expression of Hox genes and the corresponding histone modifications in F9 murine embryonic teratocarcinoma (EC) cells. Hox expression patterns and histone modifications were analyzed by semiquantitative RT-PCR, RNA-sequencing, and chromatin immuno-precipitation (ChIP)-PCR analyses. The Hoxc4 gene (D0) was initiated earlier than the Hoxc5 to –c10 genes (D3) upon RA treatment (day 0 [D0], day 1 [D1], and day 3 [D3]). The Hox nonexpressing D0 sample had a strong repressive marker, H3K27me3, than the D1 and D3 samples. In the D1 and D3 samples, reduced enrichment of the H3K27me3 marker was observed in the whole cluster. The active H3K4me3 marker was closely associated with the collinear expression of Hoxc genes. Thus, the Hoxc4 gene (D1) and all Hoxc genes (D3) expressed H3K4me3 upon transcription activation. In conclusion, these data indicated that removing H3K27me3 and acquiring H3K4me3 regulated RA-induced Hoxc gene collinearity in F9 cells.

The Design of Mobile Medical Image Communication System based on CDMA 1X-EVDO for Emergency Care (CDMA2000 1X-EVDO망을 이용한 이동형 응급 의료영상 전송시스템의 설계)

  • Kang, Won-Suk;Yong, Kun-Ho;Jang, Bong-Mun;Namkoong, Wook;Jung, Hai-Jo;Yoo, Sun-Kook;Kim, Hee-Joung
    • Proceedings of the Korean Society of Medical Physics Conference
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    • 2004.11a
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    • pp.53-55
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    • 2004
  • In emergency cases, such as the severe trauma involving the fracture of skull, spine, or cervical bone, from auto accident or a fall, and/or pneumothorax which can not be diagnosed exactly by the eye examination, it is necessary the radiological examination during transferring to the hospital for emergency care. The aim of this study was to design and evaluate the prototype of mobile medical image communication system based on CDMA 1X EVDO. The system consists of a laptop computer used as a transmit DICOM client, linked with cellular phone which support to the CDMA 1X EVDO communication service, and a receiving DICOM server installed in the hospital. The DR images were stored with DICOM format in the storage of transmit client. Those images were compressed into JPEG2000 format and transmitted from transmit client to the receiving server. All of those images were progressively transmitted to the receiving server and displayed on the server monitor. To evaluate the image quality, PSNR of compressed image was measured. Also, several field tests had been performed using commercial CDMA2000 1X-EVDO reverse link with the TCP/IP data segments. The test had been taken under several velocity of vehicle in seoul areas.

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