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( Min Kyun Na ),( Yong Tae Jeong ),( Xian Li ),( Fansi Jin ),( Seung Lark Hwang ),( Geum Jin Kim ),( Ju Hye Yang ),( Young Chae Chang ),( Dong Soo Kim ),( Cheorl Ho Kim ),( Hyeun Wook Chang ) 영남대학교 약품개발연구소 2015 영남대학교 약품개발연구소 연구업적집 Vol.25 No.-
The effect of butanol extracts of the skin of Anguilla japonica (BESA) on endoplasmic reticulum (ER) stress-induced insulin resistance in L6 myotubes was investigated. Western blotting revealed that BESA increased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and stimulated glucose uptake in L6 myotubes. Stimulation of AMPK and glucose uptake by BESA were significantly (p<0.05) reduced by siRNA LKB1 or siRNA AMPK, compared with controls, suggesting that enhanced glucose uptake by BESA was predominantly accomplished via an LKB1-mediated AMPK activation pathway. In addition, BESA effectively reduced phosphorylation of ER stress markers, RNA-activated protein kinaselike ER resident kinase, JNK, and significantly (p<0.01) increased glucose uptake via AMPK activation in tunicamycin-treated L6 myotubes, compared with controls. Improvement of insulin sensitivity under ER stress conditions by BESA is predominantly accomplished via an LKB1- AMPK-dependent pathway.
Epigenetic memory in gene regulation and immune response
( Min Young Kim ),( Ji Eun Lee ),( Lark Kyun Kim ),( Taesoo Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2019 BMB Reports Vol.52 No.2
Cells must fine-tune their gene expression programs for optimal cellular activities in their natural growth conditions. Transcriptional memory, a unique transcriptional response, plays a pivotal role in faster reactivation of genes upon environmental changes, and is facilitated if genes were previously in an active state. Hyper-activation of gene expression by transcriptional memory is critical for cellular differentiation, development, and adaptation. TREM (Transcriptional REpression Memory), a distinct type of transcriptional memory, promoting hyper-repression of unnecessary genes, upon environmental changes has been recently reported. These two transcriptional responses may optimize specific gene expression patterns, in rapidly changing environments. Emerging evidence suggests that they are also critical for immune responses. In addition to memory B and T cells, innate immune cells are transcriptionally hyperactivated by restimulation, with the same or different pathogens known as trained immunity. In this review, we briefly summarize recent progress in chromatin-based regulation of transcriptional memory, and its potential role in immune responses. [BMB Reports 2019; 52(2): 127-132]
Seo, Hyang-Hee,Lee, Se-Yeon,Lee, Chang Youn,Kim, Ran,Kim, Pilseog,Oh, Sekyung,Lee, Hojin,Lee, Min Young,Kim, Jongmin,Kim, Lark Kyun,Hwang, Ki-Chul,Chang, Woochul S. Karger 2017 Journal of vascular research Vol.54 No.2
<P>Adult stem cells have been studied as a promising therapeutic modality for the functional restoration of the damaged heart. In the present study, a strategy for enhancing the angiogenic efficacy of human mesenchymal stem cells (hMSCs) using micro-RNA was examined. We investigated whether micro-RNA-146a (miR-146a) influences the secretion of vascular endothelial growth factor (VEGF) and angiogenesis of MSCs. Our data indicated that miR-146a-transfected hMSCs (hMSC<SUP>miR-146a</SUP>) decreased the expression of neurofibromin 2, an inhibitor of p21-activated kinase-1 (PAK1). miR-146a also increased the expression of Ras-related C3 botulinum toxin substrate 1 and PAK1, which are known to induce VEGF expression, and the formation of vascular branches was increased in hMSC<SUP>miR-146a</SUP> compared to hMSCs treated with VEGF. VEGF and p-Akt were increased in hMSC<SUP>miR-146a</SUP>. Furthermore, injection of hMSC<SUP>miR-146a</SUP> after ischemia/reperfusion (I/R) injury led to a reduction of fibrosis area and increased VEGF expression, confirming the regenerative capacity such as reparative angiogenesis in the infarcted area. Cardiac functions in I/R injury were improved following injection of hMSC<SUP>miR-146a</SUP> compared to the I/R group. Taken together, these data suggest that miR-146 is a novel microRNA that regulates VEGF expression, and its use may be an effective strategy for enhancing the therapeutic efficacy of hMSC transplantation into the I/R-injured heart.</P>
OASL1 Traps Viral RNAs in Stress Granules to Promote Antiviral Responses
Kang, Ji-Seon,Hwang, Yune-Sahng,Kim, Lark Kyun,Lee, Sujung,Lee, Wook-Bin,Kim-Ha, Jeongsil,Kim, Young-Joon Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.3
Oligoadenylate synthetase (OAS) protein family is the major interferon (IFN)-stimulated genes responsible for the activation of RNase L pathway upon viral infection. OAS-like (OASL) is also required for inhibition of viral growth in human cells, but the loss of one of its mouse homolog, OASL1, causes a severe defect in termination of type I interferon production. To further investigate the antiviral activity of OASL1, we examined its subcellular localization and regulatory roles in IFN production in the early and late stages of viral infection. We found OASL1, but not OASL2, formed stress granules trapping viral RNAs and promoted efficient RLR signaling in early stages of infection. Stress granule formation was dependent on RNA binding activity of OASL1. But in the late stages of infection, OASL1 interacted with IRF7 transcripts to inhibit translation resulting in down regulation of IFN production. These results implicate that OASL1 plays context dependent functions in the antiviral response for the clearance and resolution of viral infections.