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Overexpression of Rcan1-1L Inhibits Hypoxia-Induced Cell Apoptosis through Induction of Mitophagy

  • Sun, Lijun;Hao, Yuewen;An, Rui;Li, Haixun;Xi, Cong;Shen, Guohong
    • Molecules and Cells
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    • v.37 no.11
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    • pp.785-794
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    • 2014
  • Mitophagy, a cellular process that selectively targets dysfunctional mitochondria for degradation, is currently a hot topic in research into the pathogenesis and treatment of many human diseases. Considering that hypoxia causes mitochondrial dysfunction, which results in cell death, we speculated that selective activation of mitophagy might promote cell survival under hypoxic conditions. In the present study, we introduced the Regulator of calcineurin 1-1L (Rcan1-1L) to initiate the mitophagy pathway and aimed to evaluate the effect of Rcan1-1L-induced mitophagy on cell survival under hypoxic conditions. Recombinant adenovirus vectors carrying Rcan1-1L were transfected into human umbilical vein endothelial cells and human adult cardiac myocytes. Using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay and Trypan blue exclusion assay, Rcan1-1L overexpression was found to markedly reverse cell growth inhibition induced by hypoxia. Additionally, Rcan1-1L overexpression inhibited cell apoptosis under hypoxic conditions, as detected by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) apoptosis assay. Meanwhile, the mitochondria-mediated cell apoptotic pathway was inhibited by Rcan1-1L. In contrast, knockdown of Rcan1-1L accelerated hypoxia-induced cell apoptosis. Moreover, Rcan1-1L overexpression significantly reduced mitochondrial mass, decreased depolarized mitochondria, and downregulated ATP and reactive oxygen species production. We further delineated that the loss of mitochondrial mass was due to the activation of mitophagy induced by Rcan1-1L. Rcan1-1L overexpression activated autophagy flux and promoted translocation of the specific mitophagy receptor Parkin into mitochondria from the cytosol, whereas inhibition of autophagy flux resulted in the accumulation of Parkin-loaded mitochondria. Finally, we demonstrated that mitochondrial 1permeability transition pore opening was significantly increased by Rcan1-1L overexpression, which suggested that Rcan1-1L might evoke mitophagy through regulating mitochondrial permeability transition pores. Taken together, we provide evidence that Rcan1-1L overexpression induces mitophagy, which in turn contributes to cell survival under hypoxic conditions, revealing for the first time that Rcan1-1L-induced mitophagy may be used for cardioprotection.

Ca2+/calmodulin-dependent regulation of polycystic kidney disease 2-like-1 by binding at C-terminal domain

  • Baik, Julia Young;Park, Eunice Yon June;So, Insuk
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.3
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    • pp.277-286
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    • 2020
  • Polycystic kidney disease 2-like-1 (PKD2L1), also known as polycystin-L or TRPP3, is a non-selective cation channel that regulates intracellular calcium concentration. Calmodulin (CaM) is a calcium binding protein, consisting of N-lobe and C-lobe with two calcium binding EF-hands in each lobe. In previous study, we confirmed that CaM is associated with desensitization of PKD2L1 and that CaM N-lobe and PKD2L1 EF-hand specifically are involved. However, the CaM-binding domain (CaMBD) and its inhibitory mechanism of PKD2L1 have not been identified. In order to identify CaM-binding anchor residue of PKD2L1, single mutants of putative CaMBD and EF-hand deletion mutants were generated. The current changes of the mutants were recorded with whole-cell patch clamp. The calmidazolium (CMZ), a calmodulin inhibitor, was used under different concentrations of intracellular. Among the mutants that showed similar or higher basal currents with that of the PKD2L1 wild type, L593A showed little change in current induced by CMZ. Co-expression of L593A with CaM attenuated the inhibitory effect of PKD2L1 by CaM. In the previous study it was inferred that CaM C-lobe inhibits channels by binding to PKD2L1 at 16 nM calcium concentration and CaM N-lobe at 100 nM. Based on the results at 16 nM calcium concentration condition, this study suggests that CaM C-lobe binds to Leu-593, which can be a CaM C-lobe anchor residue, to regulate channel activity. Taken together, our results provide a model for the regulation of PKD2L1 channel activity by CaM.

The relationship between uric acid and anemia in Korean adults with chronic kidney disease (국내 만성신장질환자에서 나타나는 요산과 빈혈과의 관련성)

  • Seung Bum Yang
    • Journal of the Health Care and Life Science
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    • v.11 no.1
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    • pp.141-147
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    • 2023
  • The present study was conducted to assess the relationship between hyperuricemia and anemia in Korean adults with chronic kidney disease (CKD). Data from 557 adults (age ≥ 20 years) in the Eighth Korean National Health and Nutrition Examination Survey (2019-2021) were analyzed. Several key findings were identified. First, after adjusting for the related variables, the odds ratio (OR) of anemia (hemoglobin [Hb] < 13.0 mg/dL in men or < 12 mg/dL in women), using the normouricemia group (uric acid [UA] < 7.0 mg/dL in men or < 6.0 mg/dL in women) as a reference, was positively significant for the hyperuricemia group (uric acid [UA] ≥ 7.0 mg/dL in men or ≥ 6.0 mg/dL in women) in overall population (odds ratio [OR], 1.719; 95% confidence interval [CI], 1.371-2.942), men (OR, 2.008; 95% CI, 1.013-3.165), and women (OR, 2.246; 95% CI, 1.315-3.835). In conclusions, hyperuricemia was associated with an increase in anemia in both Korean men and women with chronic kidney disease.

A Study on Quantity and Quality of Collected Rainwater by Collected Materials (우수 이용을 위한 포집재료별 포집수량과 수질에 관한 연구)

  • Lee, Young-Bok;Lee, Seung-Keun;Wang, Chang-Keun
    • Journal of Korean Society of Water and Wastewater
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    • v.18 no.1
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    • pp.66-72
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    • 2004
  • In this study, quantity and quality of collected rainwater by sand, gravel, soil, lawn and concrete surface, as collection materials were investigated and Rainwater Collection Prediction Model was developed to predict the amount of collected rainwater. The quantity of collected rainwater in concrete surface, gravel, sand, soil and lawn collection system was 1,067L(93.2%), 1,006L(87.8%), 902L(78.8%), 800L(69.9%), 788.5L(68.8%) for 8 months period, respectively. The average turbidity of collected rainwater in concrete surface, gravel, sand, soil and lawn collection system was 3.2NTU, 2.2NTU, 1.9NTU, 1.7NTU, 1.5NTU for 8 months period, respectively. For sand collection material, predicted amount by the Model and actual collected amount were 931.5L and 902L, which were very closed. For gravel collection material, predicted amount by Model and actual collected amount were 1,028.21. and 1,006L, which were very closed. To simulate the optimal rainwater storage volume, the rainfall and evaporation data in Dae-jeon city were used. For sand collection system with 30m2 area, the maximum storage volume was $17m^3$ and 62% of the year was secured for use of 240L/day.

Water Environmental Factors and Trophic States in Lake Daecheong (대청호의 수질 환경요인과 영양단계 평가)

  • Park, Jong-Geun
    • Korean Journal of Ecology and Environment
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    • v.38 no.3 s.113
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    • pp.382-392
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    • 2005
  • Data were collected in Lake Daecheong from March 1997 to October 2002 and used to understand an annual change of water environmental factors and trophic states. The surface water temperature was ranged from $3.2^{\circ}C$ to $33.1^{\circ}C$ In the middle of February, water temperature was the lowest. Turbidity was ranged from 0.1 to 203.5 NTU, but the values of above 30 NTU were only measured at site 1. The total mean values of COD and Chl a were $3.6{\pm}1.4\;mg\;O_2\;L^{-1}$, $9.3{\pm}12.8\;{\mu}g\;L^{-1}$respectively. The concentrations of TP and TN were ranged from 0.14 to 5.09 mg N $L^{-1}$, 1 to $247\;{\mu}g\;P\;L^{-1}$ respectively. The total mean value of TN/TP ratio was $98.7{\pm}56.2$. The trophic states were ranged from mesotrophic to eutrophic in Lake Daecheong.

Effect of Growth Regulators on the Organ Differentiation and the Growth from the Axillary Bud of Sweetpotatoes in Vitro Culture (고구마의 액아배양에서 생장조절물질이 기관분화 및 생장에 미치는 영향)

  • Byong-Ho Chang
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.29 no.4
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    • pp.401-408
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    • 1984
  • This study was conducted to determine the optimum concentrations of growth regulators and their responses on the clonal propagation in axillary bud culture. Cultivars, Hongmi and Shinmi, responded differently to the levels of growth regulators, proliferation rate and shoot growth. The shoot and root of Hongmi cultivar in axillary bud culture were conspicuously induced by combination of NAA(0.1mg/l) and Kinetin(1mg/l) while Shinmi cultivar were affected by the single concentration of Kinetin(1mg/l) and BA(0.1mg/l), and also by the combination of NAA(0.1mg/l) and Kinetin(1mg/l). Better shoot growth and root initiation were obtained in the combination of NAA(0.1mg/l) and Kinetin(1mg/l) regardless of cultivars used when 5mm axillary buds were cultured. The shoots regenerated at the high levels of BA(1-5mg/l) were abnormally thicker and narrower leaves than normal plants and short in shoot height. Frequencies of abnormal plants were higher than that of the low level (0.1mg/l) of BA.

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Choline and Betaine Concentrations in Breast Milk of Korean Lactating Women and the Choline and Betaine Intakes of Their Infants (한국 수유부 유즙의 콜린과 베타인 농도 및 영아의 콜린과 베타인 섭취량)

  • Jeong, Han-Ok;Suh, Yoon-Suk;Chung, Young-Jin
    • Journal of Nutrition and Health
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    • v.43 no.6
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    • pp.588-596
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    • 2010
  • Most nutrients taken by pregnant women are secreted into their breast milk. Food contains choline together with betaine, and in human body choline is oxidized to betaine which transfer methyl group. The aim of the study was to estimate the concentrations of choline and betaine in breast milk of Korean lactating women and the choline and betaine intakes of their infants. Total choline, free choline and betaine concentrations in breast milk of some lactating women living in Daejon Metropolitan city were analyzed every month by using HPLC-MS and enzymatic method during the first five months. Total choline concentrations of breast milks were 157.64 mg/L (1.52 mmol/L), 157.83 mg/L (1.52 mmol/L), 165.99 mg/L (1.60 mmol/L), 153.67 mg/L (1.48 mmol/L), 145.05 mg/L (1.39 mmol/L) by month after delivery for five months. The concentrations of total choline and free choline in breast milks were not significantly changed for the five months while the betaine concentrations gradually decreased. Daily intake of total choline of the infants appears to be adequate for the infant's requirement according to the US DRI; 124.6 mg/d, 120.9 mg/d, 126.5 mg/d 104.1 mg/d from 2nd to 5th month after birth. Free choline and betaine intakes of the infants were not significantly changed during the four months except showing decrease in betaine intake per kg body weight. Choline intakes of the infants more correlated with choline concentrations of the breast milks (r = 0.982, p = 0.000) than intake amount of the breast milk (r = 0.414, p = 0.028). These results suggest that the choline intake of Korean breast-fed infants appears to be adequate and the intake could be affected by the choline concentration of the breast milk.

ULTRAPRODUCTS OF LOCALLY CONVEX SPACES

  • Kang, Si-Ho
    • Bulletin of the Korean Mathematical Society
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    • v.27 no.2
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    • pp.189-196
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    • 1990
  • In this paper, we try to generalize ultraproducts in the category of locally convex spaces. To do so, we introduce D-ultracolimits. It is known [7] that the topology on a non-trivial ultraproduct in the category T $V^{ec}$ of topological vector spaces and continuous linear maps is trivial. To generalize the category Ba $n_{1}$ of Banach spaces and linear contractions, we introduce the category L $C_{1}$ of vector spaces endowed with families of semi-norms closed underfinite joints and linear contractions (see Definition 1.1) and its subcategory, L $C_{2}$ determined by Hausdorff objects of L $C_{1}$. It is shown that L $C_{1}$ contains the category LC of locally convex spaces and continuous linear maps as a coreflective subcategory and that L $C_{2}$ contains the category Nor $m_{1}$ of normed linear spaces and linear contractions as a coreflective subcategory. Thus L $C_{1}$ is a suitable category for the study of locally convex spaces. In L $C_{2}$, we introduce $l_{\infty}$(I. $E_{i}$ ) for a family ( $E_{i}$ )$_{i.mem.I}$ of objects in L $C_{2}$ and then for an ultrafilter u on I. we have a closed subspace $N_{u}$ . Using this, we construct ultraproducts in L $C_{2}$. Using the relationship between Nor $m_{1}$ and L $C_{2}$ and that between Nor $m_{1}$ and Ba $n_{1}$, we show thatour ultraproducts in Nor $m_{1}$ and Ba $n_{1}$ are exactly those in the literatures. For the terminology, we refer to [6] for the category theory and to [8] for ultraproducts in Ba $n_{1}$..

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Behavior of Listeria monocytogenes in skin milk during fermentation by Lactobacillus bulgaricus and Streptococcus lactis (Lactobacillus bulgaricus와 Streptococcus lactis 발효탈지유에서의 Listeria monocytogenes의 생존추이)

  • 박경식
    • Journal of environmental and Sanitary engineering
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    • v.12 no.1
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    • pp.85-95
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    • 1997
  • Behavior of Listeria monocytogenes in Skim milk during fermentation by Lactobacillus bulgaricus YI-2 and Streptococcus lactis FYI-1 were determined. Autoclaved skim milk was inoculated with ca. 10$^{3}$ L. monocytogenes (Strain LM91-1 or LM 96-2) cells/ml, and with 5.0, 1.0, 0.5 or 0.1% of a milk culture of either L. bulgaricus TI-2 or S. lactis FYI-1. Skim milk containing ca. 10$^{3}$ L. monocytogenes was incubated at 37 or 42$\circ $C for 15 h with L. bulgaricus YI-2, and at 21 or 30$\circ $C for 15 h with S. lactis FYI-1. Cultured skim milks were stored at 4$\circ $C in the refrigerater. Samples were plated on Oxford Agar with oxford antimicrobic supplement to enumerate L. monocytogenes and on either modified MRS agar to enumerate lactic acid bacteria. L. monocytogenes survived the 15-h fermentation with S. lactis FYI-1 in all combinations of level of inoculum and temperature of incubation, but inhibition of growth ranged from 94 to 100%. When incubated with over the 1.0% of L. bulgaricus, L. monocytogenes inhibited or disappeared in fermented skim milk from 9 h after incubation. Especially, incubation at 42$\circ $C with 5.0% L. bulgaricus YI-2 as inoculum appeared to be the most effective inhibitory combination for strain LM 91-1, causing 100% inhibition in growth based on maximum papulation attained. In most instances of incubated with L. bulgaricus YI-2, growth of the pathogene appeared to be completely inhibited when the pH dropped below 4.38.

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