miRNA and cholesterol homeostasis

Jeon, Tae-Il,Osborne, Timothy F. Elsevier 2016 Biochimica et biophysica acta, Molecular and cell Vol.1861 No.12

<P>MicroRNAs (miRNAs) have recently emerged as a novel class of epigenetic regulators of gene expression. They are systemically involved in the control of lipid metabolism through a complex interactive mechanism that involves gene regulatory networks. Hence, they can contribute to defective lipid metabolism and metabolic diseases. Here, we review recent advances in the roles of lipid-sensing transcription factors in regulating miRNA gene networks, as well as miRNA expression and function in the regulation of cholesterol metabolism. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernandez-Hernando and Yajaira Suarez (C) 2016 Published by Elsevier B.V.</P>

DEVELOPING A SMART GRID THAT CUSTOMERS CAN AFFORD

Wooyoung Jeon,Jung Youn Mo,Timothy Mount 한국신재생에너지학회 2015 AFORE Vol.2015 No.11

Developing a Smart Grid that Customers can Afford: The Impact of Deferrable Demand

( Wooyoung Jeon ),( Jung Youn Mo ),( Timothy D. Mount ) 한국환경경제학회, 한국자원경제학회 ( 구 한국환경경제학회 ) 2015 한국환경경제학회 학술발표논문집 Vol.2015 No.하계

With more electricity generated from renewable sources, the importance of effective storage capacity is increasing due to its capability to mitigate the inherent variability of these sources, such as wind and solar power. However, the cost of dedicated storage is high and all customers eventually have to pay. Deferrable demand offers an alternative form of storage that is potentially less expensive because the capital cost is shared between providing an energy service and supporting the grid. This paper presents an empirical analysis to illustrate the beneficial effects of Plug-in Hybrid Electric Vehicles (PHEV) and thermal storage on the total system cost using data for a hot summer day in New York City. The analysis shows how customers can reduce total system costs and their bills by 1) shifting load from expensive peak periods to less expensive off-peak periods, 2) reducing the amount of installed conventional generating capacity needed to maintain System Adequacy, and 3) providing ramping services to mitigate the variability of generation from renewable sources. Moreover, this paper demonstrates economic benefits of different types of customers with different deferrable demand capabilities under two bill payment policies, flat price payment and optimum price payment, and it finally shows how long it takes for customers to fully pay back their initial capital costs of PHEV or thermal storage under two different policies.

Postdoc Colloquium 2 : Implications for Familial Hypercholesterolemia from Structure of the LDL Receptor YWTD-EGF Domain Pair

( Hye Sung Jeon ),( Wu Yi Meng ),( Junichi Takagi ),( Michael J. Eck ),( Timothy A. Springer ),( Stephen C. Blacklow ) 한국생화학분자생물학회 (구 한국생화학회) 2002 생화학분자생물학회 춘계학술발표논문집 Vol.2002 No.-

SREBP-1c Ablation Protects Against ER Stress-induced Hepatic Steatosis by Preventing Impaired Fatty Acid Oxidation

Young-Seung Lee(이영승),Timothy F. Osborne(티모씨 에프 오스본),Young-Kyo Seo(서영교),Tae-Il Jeon(전태일) 한국생명과학회 2021 생명과학회지 Vol.31 No.9

간 소포체(ER) 스트레스는 비알콜성지방간과 인슐린 저항성의 발달에 기여하고, unfolded protein response(UPR)의 구성요소는 지질 대사를 조절한다. 최근 연구에 따르면 ER 스트레스와 비정상적인 세포 지질 대사 사이의 연관성이 보고되었으며, 이 과정에서 지질 대사의 중심 조절자인 sterol regulatory element binding proteins(SREBPs)의 관련성이 확인되었다. 그러나 ER 스트레스 동안 지질 대사를 조절하는 SREBP의 정확한 역할과 비알콜성지방간에 대한 기여는 아직 밝혀지지 않았다. 본 연구에서 SREBP-1c 결핍은 UPR, 염증 및 지방산 산화 조절을 통해 ER 스트레스에 의해 유도된 비알콜성지방간으로부터 생쥐를 보호한다는 것을 보여준다. SREBP-1c는 inositol requiring kinase 1α (IRE1α) 발현을 직접적으로 조절하고 ER 스트레스에 의해 유도된 tumor necrosis factor-α의 활성화를 매개하여 peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1α)의 감소와 그에 따른 지방산 산화의 장애를 유발한다. 그러나, SREBP-1c의 유전적 결핍은 이러한 현상을 보호하여 간 염증과 지방축적을 완화시킨다. SREBP-1c 결핍이 ER 스트레스에 의해 유도된 염증 신호를 방지하는 메커니즘은 아직 밝혀지지 않았지만, SREBP-1c가 결핍된 Kupffer 세포에서 IRE1α 신호의 변화가 염증 신호에 관여할 수 있을 것으로 생각된다. 본 연구결과는 SREBP-1c가 ER 스트레스에 의해 유도된 비알콜성지방간에서 UPR 및 염증의 조절에 중요한 역할을 함을 시사한다. Hepatic endoplasmic reticulum (ER) stress contributes to the development of steatosis and insulin resistance. The components of unfolded protein response (UPR) regulate lipid metabolism. Recent studies have reported an association between ER stress and aberrant cellular lipid control; moreover, research has confirmed the involvement of sterol regulatory element-binding proteins (SREBPs)-the central regulators of lipid metabolism-in the process. However, the exact role of SREBPs in controlling lipid metabolism during ER stress and its contribution to fatty liver disease remain unknown. Here, we show that SREBP-1c deficiency protects against ER stress-induced hepatic steatosis in mice by regulating UPR, inflammation, and fatty acid oxidation. SREBP-1c directly regulated inositol-requiring kinase 1α (IRE1α) expression and mediated ER stress-induced tumor necrosis factor-α activation, leading to a reduction in expression of peroxisome proliferator-activated receptor γ coactivator 1-α and subsequent impairment of fatty acid oxidation. However, the genetic ablation of SREBP-1c prevented these events, alleviating hepatic inflammation and steatosis. Although the mechanism by which SREBP-1c deficiency prevents ER stress-induced inflammatory signaling remains to be elucidated, alteration of the IRE1α signal in SREBP-1c-depleted Kupffer cells might be involved in the signaling. Overall, the results suggest that SREBP-1c plays a crucial role in the regulation of UPR and inflammation in ER stress-induced hepatic steatosis.

Coupled Lattice Polarization and Ferromagnetism in Multiferroic NiTiO₃ Thin Films

Varga, Tamas,Droubay, Timothy C.,Kovarik, Libor,Nandasiri, Manjula I.,Shutthanandan, Vaithiyalingam,Hu, Dehong,Kim, Bumsoo,Jeon, Seokwoo,Hong, Seungbum,Li, Yulan,Chambers, Scott A. American Chemical Society 2017 ACS APPLIED MATERIALS & INTERFACES Vol.9 No.26

<P>Polarization-induced weak ferromagnetism (WFM) was demonstrated a few years back in LiNbO3-type compounds, MTiO3 (M = Fe, Mn, Ni). Although the coexistence of ferroelectric polarization and ferromagnetism has been demonstrated in this rare multiferroic family before, first in bulk FeTiO3, then in thin-film NiTiO3, the coupling of the two order parameters has not been confirmed Here, we report the stabilization of polar, ferromagnetic NiTiO3 by oxide epitaxy on a LiNbO3 substrate utilizing tensile strain and demonstrate the theoretically predicted coupling between its polarization and ferromagnetism by X-ray magnetic circular dichroism under applied fields. The experimentally observed direction of ferroic ordering in the film is supported by simulations using the phase-field approach. Our work validates symmetry-based criteria and first-principles calculations of the coexistence of ferroelectricity and WFM in MTiO3 transition metal titanates crystallizing in the LiNbO3 structure. It also demonstrates the applicability of epitaxial strain as a viable alternative to high-pressure crystal growth to stabilize metastable materials and a valuable tuning parameter to simultaneously control two ferroic order parameters to create a multiferroic. Multiferroic NiTiO3 has potential applications in spintronics where ferroic switching is used, such as new four-stage memories and electromagnetic switches.</P>

Hypoxia-inducible factor-dependent production of profibrotic mediators by hypoxic hepatocytes

Copple, Bryan L.,Bustamante, Juan J.,Welch, Timothy P.,Kim, Nam Deuk,Moon, Jeon-Ok Blackwell Publishing Ltd 2009 Liver International Vol.29 No.7

<P>Abstract</P><P>Background/Aims</P><P>During the development of liver fibrosis, mediators are produced that stimulate cells in the liver to differentiate into myofibroblasts and to produce collagen. Recent studies demonstrated that the transcription factor, hypoxia-inducible factor-1α (HIF-1α), is critical for upregulation of profibrotic mediators, such as platelet-derived growth factor-A (PDGF-A), PDGF-B and plasminogen activator inhibitor-1 (PAI-1) in the liver, during the development of fibrosis. What remains unknown is the cell type-specific regulation of these genes by HIF-1α in liver cell types. Accordingly, the hypothesis was tested that HIF-1α is activated in hypoxic hepatocytes and regulates the production of profibrotic mediators by these cells.</P><P>Methods</P><P>In this study, hepatocytes were isolated from the livers of control and HIF-1α- or HIF-1β-deficient mice and exposed to hypoxia.</P><P>Results</P><P>Exposure of primary mouse hepatocytes to 1% oxygen stimulated nuclear accumulation of HIF-1α and upregulated PAI-1, vascular endothelial cell growth factor and the vasoactive peptides adrenomedullin-1 (ADM-1) and ADM-2. In contrast, the levels of PDGF-A and PDGF-B mRNAs were unaffected in these cells by hypoxia. Exposure of HIF-1α-deficient hepatocytes to 1% oxygen only partially prevented upregulation of these genes, suggesting that other hypoxia-regulated transcription factors, such as HIF-2α, may also regulate these genes. In support of this, HIF-2α was activated in hypoxic hepatocytes, and exposure of HIF-1β-deficient hepatocytes to 1% oxygen completely prevented upregulation of PAI-1, vascular endothelial cell growth factor and ADM-1, suggesting that HIF-2α may also contribute to upregulation of these genes in hypoxic hepatocytes.</P><P>Conclusions</P><P>Collectively, our results suggest that HIFs may be important regulators of profibrotic and vasoactive mediators by hypoxic hepatocytes.</P>

P53 Impairs Endothelium-Dependent Vasomotor Function Through Transcriptional Upregulation of P66shc

Kim, Cuk-Seong,Jung, Saet-Byel,Naqvi, Asma,Hoffman, Timothy A.,DeRicco, Jeremy,Yamamori, Tohru,Cole, Marsha P.,Jeon, Byeong-Hwa,Irani, Kaikobad Ovid Technologies Wolters Kluwer -American Heart A 2008 Circulation research Vol.103 No.12

<P>The transcription factor, p53, and the adaptor protein, p66shc, both play essential roles in promoting oxidative stress in the vascular system. However, the relationship between the two in the context of endothelium-dependent vascular tone is unknown. Here, we report a novel, evolutionarily conserved, p53-mediated transcriptional mechanism that regulates p66shc expression and identify p53 as an important determinant of endothelium-dependent vasomotor function. We provide evidence of a p53 response element in the promoter of p66shc and show that angiotensin II-induced upregulation of p66shc in endothelial cells is dependent on p53. In addition, we demonstrate that downregulation of p66shc expression, as well as inhibition of p53 function in mice, mitigates angiotensin II-induced impairment of endothelium-dependent vasorelaxation, decrease in bioavailable nitric oxide, and hypertension. These findings reveal a novel p53-dependent transcriptional mechanism for the regulation of p66shc expression that is operative in the vascular endothelium and suggest that this mechanism is important in impairing endothelium-dependent vascular relaxation.</P>

Histone Deacetylase 3 Antagonizes Aspirin-Stimulated Endothelial Nitric Oxide Production by Reversing Aspirin-Induced Lysine Acetylation of Endothelial Nitric Oxide Synthase

Jung, Saet-Byel,Kim, Cuk-Seong,Naqvi, Asma,Yamamori, Tohru,Mattagajasingh, Ilwola,Hoffman, Timothy A.,Cole, Marsha P.,Kumar, Ajay,DeRicco, Jeremy S.,Jeon, Byeong-Hwa,Irani, Kaikobad Ovid Technologies Wolters Kluwer -American Heart A 2010 Circulation research Vol.107 No.7

Estrogen-related receptor γ controls sterol regulatory element-binding protein-1c expression and alcoholic fatty liver

Kim, Don-Kyu,Kim, Yong-Hoon,Lee, Jae-Ho,Jung, Yoon Seok,Kim, Jina,Feng, Rilu,Jeon, Tae-Il,Lee, In-Kyu,Cho, Sung Jin,Im, Seung-Soon,Dooley, Steven,Osborne, Timothy F.,Lee, Chul-Ho,Choi, Hueng-Sik Elsevier 2019 Biochimica et biophysica acta, Molecular and cell Vol.1864 No.12

<P><B>Abstract</B></P> <P>Although SREBP-1c regulates key enzymes required for hepatic <I>de novo</I> lipogenesis, the mechanisms underlying transcriptional regulation of SREBP-1c in pathogenesis of alcoholic fatty liver is still incompletely understood. In this study, we investigated the role of ERRγ in alcohol-mediated hepatic lipogenesis and examined the possibility to ameliorate alcoholic fatty liver through its inverse agonist. Hepatic ERRγ and SREBP-1c expression was increased by alcohol-mediated activation of CB<SUB>1</SUB> receptor signaling. Deletion and mutation analyses of the <I>Srebp-1c</I> gene promoter showed that ERRγ directly regulates <I>Srebp-1c</I> gene transcription <I>via</I> binding to an ERR-response element. Overexpression of ERRγ significantly induced SREBP-1c expression and fat accumulation in liver of mice, which were blocked in <I>Srebp-1c</I>-knockout hepatocytes. Conversely, liver-specific ablation of <I>ERRγ</I> gene expression attenuated alcohol-mediated induction of SREBP-1c expression. Finally, an ERRγ inverse agonist, GSK5182, significantly ameliorates fatty liver disease in chronically alcohol-fed mice through inhibition of SREBP-1c-mediated fat accumulation. ERRγ mediates alcohol-induced hepatic lipogenesis by upregulating SREBP-1c expression, which can be blunted by the inverse agonist for ERRγ, which may be an attractive therapeutic strategy for the treatment of alcoholic fatty liver disease in human.</P> <P><B>Highlights</B></P> <P> <UL> <LI> ERRγ is induced by alcohol-mediated activation of CB<SUB>1</SUB> receptor signaling. </LI> <LI> ERRγ increases hepatic SREBP-1c expression and alcohol-mediated hepatic lipogenesis </LI> <LI> An ERRγ inverse agonist inhibits SREBP-1c-induced hepatic <I>de novo</I> lipogenesis. </LI> <LI> An ERRγ inverse agonist ameliorates alcohol fatty liver disease. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>