Umbilical Cord Mesenchymal Stromal Cells Affected by Gestational Diabetes Mellitus Display Premature Aging and Mitochondrial Dysfunction

Kim, Jooyeon,Piao, Ying,Pak, Youngmi Kim,Chung, Dalhee,Han, Yu Mi,Hong, Joon Seok,Jun, Eun Jeong,Shim, Jae-Yoon,Choi, Jene,Kim, Chong Jai Mary Ann Liebert 2015 STEM CELLS AND DEVELOPMENT Vol.24 No.5

<P>Human umbilical cord mesenchymal stromal cells (hUC-MSCs) of Wharton's jelly origin undergo adipogenic, osteogenic, and chondrogenic differentiation in vitro. Recent studies have consistently shown their therapeutic potential in various human disease models. However, the biological effects of major pregnancy complications on the cellular properties of hUC-MSCs remain to be studied. In this study, we compared the basic properties of hUC-MSCs obtained from gestational diabetes mellitus (GDM) patients (GDM-UC-MSCs) and normal pregnant women (N-UC-MSCs). Assessments of cumulative cell growth, MSC marker expression, cellular senescence, and mitochondrial function-related gene expression were performed using a cell count assay, senescence-associated β-galactosidase staining, quantitative real-time reverse transcription-polymerase chain reaction, immunoblotting, and cell-based mitochondrial functional assay system. When compared with N-UC-MSCs, GDM-UC-MSCs showed decreased cell growth and earlier cellular senescence with accumulation of p16 and p53, even though they expressed similar levels of CD105, CD90, and CD73 MSC marker proteins. GDM-UC-MSCs also displayed significantly lower osteogenic and adipogenic differentiation potentials than N-UC-MSCs. Furthermore, GDM-UC-MSCs exhibited a low mitochondrial activity and significantly reduced expression of the mitochondrial function regulatory genes ND2, ND9, COX1, PGC-1α, and TFAM. Here, we report intriguing and novel evidence that maternal metabolic derangement during gestation affects the biological properties of fetal cells, which may be a component of fetal programming. Our findings also underscore the importance of the critical assessment of the biological impact of maternal-fetal conditions in biological studies and clinical applications of hUC-MSCs.</P>

Role of hypothalamic Foxo1 in the regulation of food intake and energy homeostasis

Kim, Min-Seon,Pak, Youngmi K,Jang, Pil-Geum,Namkoong, Cherl,Choi, Yon-Sik,Won, Jong-Chul,Kim, Kyung-Sup,Kim, Seung-Whan,Kim, Hyo-Soo,Park, Joong-Yeol,Kim, Young-Bum,Lee, Ki-Up Nature Publishing Group 2006 NATURE NEUROSCIENCE Vol.9 No.7

Insulin signaling in the hypothalamus plays a role in maintaining body weight. Studies suggest that the forkhead transcription factor Foxo1 is an important mediator of insulin signaling in peripheral tissues. Here we demonstrate that in normal mice, hypothalamic Foxo1 expression is reduced by the anorexigenic hormones insulin and leptin. These hormones' effects on feeding are inhibited when hypothalamic Foxo1 is activated, establishing a new signaling pathway through which insulin and leptin regulate food intake in hypothalamic neurons. Moreover, activation of Foxo1 in the hypothalamus increases food intake and body weight, whereas inhibition of Foxo1 decreases both. Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway, but suppresses the transcription of anorexigenic proopiomelanocortin by antagonizing the activity of signal transducer–activated transcript-3 (STAT3). Our data suggest that hypothalamic Foxo1 is an important regulator of food intake and energy balance.

Serum arylhydrocarbon receptor transactivating activity is elevated in type 2 diabetic patients with diabetic nephropathy

Kim, Jin Taek,Kim, Sang Soo,Jun, Dae Won,Hwang, Young Hwan,Park, Wook‐,Ha,Pak, Youngmi Kim,Lee, Hong Kyu Wiley-Blackwell 2013 Journal of diabetes investigation Vol.4 No.5

<P><B>Abstract</B></P><P><B>Aims/Introduction</B></P><P>Evidence is emerging that exposure to persistent organic pollutants (POPs) is a risk factor for obesity‐related diseases and for diabetes mellitus (DM). We found that POPs could be measured by a cell‐based arylhydrocarbon receptor (AhR)‐dependent reporter assay. We tested if serum AhR transactivating (AHRT) activities are a risk factor for diabetic nephropathy in people with type 2 diabetes.</P><P><B>Materials and Methods</B></P><P>We enrolled diabetic patients with normoalbuminuria (<I>n </I>= 36), microalbuminuria (<I>n </I>= 29), macroalbuminuria (<I>n </I>= 8) and end‐stage renal disease (<I>n </I>= 31). Sera were tested for their AHRT activities, which were standardized by an AhR ligand, 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) and expressed as TCDD equivalents (TCDDeq pmol/L).</P><P><B>Results</B></P><P>Mean serum AHRT activities were higher in patients with microalbuminuria (40.1 ± 7.1 pmol/L), macroalbuminuria (37.4 ± 5.5 pmol/L) and end‐stage renal disease (59.1 ± 20.0 pmol/L) than in subjects with normoalbuminuria (12.7 ± 5.4 pmol/L; <I>P </I>< 0.05 for all comparisons). Serum AhR ligands showed a correlation with estimated glomerular filtration rate (eGFR;<I> r </I>= −0.663, <I>P </I>< 0.001), serum creatinine level (<I>r </I>= 0.635, <I>P </I>< 0.001), systolic blood pressure (<I>r </I>= 0.223, <I>P </I>= 0.026), glycated hemoglobim (<I>r </I>= 0.339, <I>P </I>< 0.001) and diabetic duration (<I>r </I>= 0.394, <I>P </I>< 0.001). In a multiple regression analysis, diabetic nephropathy was found to be an independent risk factor for higher AHRT activity after controlling for the confounding factors.</P><P><B>Conclusions</B></P><P>The present findings suggest serum AHRT activity, thus serum AhR ligands, is a risk factor for diabetic nephropathy. Further studies are required to clarify if an accumulation of POPs in the body is causally related to diabetic nephropathy.</P>

고지방식이와 에스트로겐이 콜레스테롤 항상성에 관련된 유전자의 발현에 미치는 영향

김준우,송지현,김영미 한국지질학회 2000 韓國脂質學會誌 Vol.10 No.2

Poster Presentation : Recruitment of Protein Kinase B/Akt by OxLDL into Lipid Raft Inactivates IRE-responsive Gene Expression in Rat Aortic Vascular Smooth Muscle Cells

( Yuna Kim ),( Bo Kyung Ryu ),( Jung Man Hong ),( Youngmi Kim Pak ) 한국지질동맥경화학회 ( 구 한국지질학회 ) 2005 한국지질동맥경화학회 추계학술발표논문집 Vol.1 No.-

Preparation and application of graphene-poly (diallyldimethylammoniumchloride)-iron oxide nanoparticles buckypaper for hydrogen peroxide detection.

You, Xueque,Kim, Jeejung,Pak, Youngmi Kim,Pak, James Jungho American Scientific Publishers 2013 Journal of Nanoscience and Nanotechnology Vol.13 No.11

<P>We have reported the preparation and characterization of a novel, freestanding, paper-like graphene (G)-poly(diallyldimethylammoniumchloride) (PDDA)-Fe3O4 nanoparticles (NPs) composite. This G-based flexible buckypaper (BP) composed of stacked G-PDDA-NP platelets exhibited excellent mechanical properties, superior electrical properties, and enzyme mimetic activity, making it potentially suitable for in electrochemical sensor applications. The negatively charged NPs were immobilized on positively charged G-PDDA through the electrostatic interaction to form nanoscale G-PDDA-NP platelets, which were further assembled by flow-directed assembly to form BP. The resulting BP has macroscopic flexibility and stiffness due to the van der Waals forces between nanoscale G-PDDA-NP platelets and interlocking-tile arrangement of the platelets. The morphology and structure of the individual G-PDDA-NP platelets and the resulting BP were analyzed by using AFM, SEM and EDX. The BP was attached to an Au or Pt electrode to construct a non-enzyme H2O2 chemical sensor. The NPs acted as a 'spacer' to increase the distance between the G sheets and decrease the chances of formation of a stacked graphitic structure, thereby increasing the surface area of the G electrode. The Fe3O4 NPs immobilized and embedded in the BP have intrinsic enzyme mimetic activity like natural peroxidase. The high surface area and excellent electrical conductivity of G improved the catalytic properties of NPs. The obtained H2O2, chemical sensor exhibited prominent electrocatalytic activity towards H2O2, with a wide linear range from 10 ppm (approximately 0.3 mM) to 800 ppm (approximately 23 mM), correlation coefficient of 0.986, and a high sensitivity of 218 microA mM(-1) x cm(-2). Such low-cost G-PDDA-NP composite BPs prepared by facile methods pave way towards novel sensors with better performance.</P>

Immunosensor Based on the ZnO Nanorod Networks for the Detection of H1N1 Swine Influenza Virus

Jang, Yunseok,Park, Jungil,Pak, Youngmi Kim,Pak, James Jungho American Scientific Publishers 2012 Journal of Nanoscience and Nanotechnology Vol.12 No.7

<P>This paper presents an immunosensor fabricated on patterned zinc oxide nanorod networks (ZNNs) for detecting the H1N1 swine influenza virus (H1N1 SIV). Nanostructured ZnO with a high isoelectric point (IEP, similar to 9.5) possesses good absorbability for proteins with low IEPs. Hydrothermally grown ZNNs were fabricated on a patterned Au electrode (0.02 cm(2)) through a lift-off process. To detect the H1N1 SIV, the sandwich enzyme-linked immunosorbent assay (ELISA) method was employed in the immunosensor. The immunosensor was evaluated in an acetate buffer solution containing 3,3',5,5'-tetramethylbenzidine (TMB) via cyclic voltammetry at various H1N1 SIV concentrations (1 pg/mL-5 ng/mL). The measurement results of the fabricated immunosensor showed that the reduction currents of TMB at 0.25 V logarithmically increased from 259.37 to 577.98 nA as the H1N1 SIV concentration changed from 1 pg/mL to 5 ng/mL. An H1N1 SIV immunosensor, based on the patterned ZNNs, was successfully realized for detecting 1 pg/mL-5 ng/mL H1N1 SIV concentrations, with a detection limit of 1 pg/mL for H1N1 SIV.</P>

Aptamer-Based Immunosensor on the ZnO Nanorods Networks

Nam, Yoonkyung,Park, Jungil,Pak, Youngmi Kim,Pak, James Jungho American Scientific Publishers 2012 Journal of Nanoscience and Nanotechnology Vol.12 No.7

<P>This paper presents the fabrication and characteristics of a new aptamer-based electrochemical immunosensor on the patterned zinc oxide nanorod networks (ZNNs) for detecting thrombin. Aptamers are single-stranded RNA or DNA sequence that binds to target materials with high specificity and affinity. An antibody-antigen-aptamer sandwich structure was employed to this immunosensor for detecting thrombin. First, hydrothermally grown ZNNs were patterned on the patterned 0.02 cm2 Au/Ti electrodes on a glass substrate by lift-off process. The high isoelectric point (IEP, approximately 9.5) of nanostructured ZnO makes it suitable for immobilizing proteins with low IEP. Then 5 microL of the 500 nM antibody was immobilized on the ZNNs electrode. 5 micro/L of the mixture of 1 microM aptamer labeled by ferrocene (Fc) and thrombin was dropped on the electrode for antibody-antigen binding. The peak oxidation currents of the immunosensors at various thrombin concentrations were measured by using cyclic voltammetry. The peak oxidation current was observed at 340 mV versus Ag/AgCl electrode, and the peak oxidation current increased linearly from 62.26 nA to 354.13 nA with the logarithmic concentration of thrombin in the range from 100 pM to 250 nM. Fabrication of an aptamer-based immunosensor for thrombin detection is a new attempt and the characteristics of the fabricated immunosensors showed that the fabricated aptamer-baded immunosensor worked electrochemically well and had a low detection limit (approximately 91.04 pM) and good selectivity.</P>

Organelle stress-induced activating transcription factor-3 downregulates low-density lipoprotein receptor expression in Sk-Hep1 human liver cells

Lim, Joo Hyun,Lee, Hyo Jung,Pak, Youngmi Kim,Kim, Won-Ho,Song, Jihyun Walter de Gruyter GmbH 2011 Biological chemistry Vol.392 No.4

Clinical Value of Serum Mitochondria-Inhibiting Substances in Assessing Renal Hazards: A Community-Based Prospective Study in Korea

최훈성,김진택,이홍규,Wook-Ha Park,Youngmi Kim Pak,이성우 대한내분비학회 2021 Endocrinology and metabolism Vol.36 No.6

Background: Mitochondrial dysfunction is strongly associated with several kidney diseases. However, no studies have evaluated the potential renal hazards of serum mitochondria-inhibiting substance (MIS) and aryl hydrocarbon receptor ligand (AhRL) levels. Methods: We used serum level of MIS and AhRL and clinical renal outcomes from 1,511 participants of a prospective communitybased cohort in Ansung. MIS was evaluated based on intracellular adenosine triphosphate (MIS-ATP) or reactive oxygen species (MIS-ROS) generation measured using cell-based assays. Results: During a mean 6.9-year follow-up, 84 participants (5.6%) developed a rapid decline in kidney function. In the lowest quartile group of MIS-ATP, patients were older and had metabolically deleterious parameters. In multivariate logistic regression analysis, higher MIS-ATP was associated with decreased odds for rapid decline: the odds ratio (OR) of 1% increase was 0.977 (95% confidence interval [CI], 0.957 to 0.998; P=0.031), while higher MIS-ROS was marginally associated with increased odds for rapid decline (OR, 1.014; 95% CI, 0.999 to 1.028; P=0.055). However, serum AhRL was not associated with the rapid decline in kidney function. In subgroup analysis, the renal hazard of MIS was particularly evident in people with hypertension and low baseline kidney function. Conclusion: Serum MIS was independently associated with a rapid decline in kidney function, while serum AhRL was not. The clinical implication of renal hazard on serum MIS requires further evaluation in future studies.