• Title/Summary/Keyword: mitochondrial proteome

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Proteomic Analysis of the Hydrophobic Fraction of Mesenchymal Stem Cells Derived from Human Umbilical Cord Blood

  • Jeong, Ju Ah;Lee, Yoon;Lee, Woobok;Jung, Sangwon;Lee, Dong-Seong;Jeong, Namcheol;Lee, Hyun Soo;Bae, Yongsoo;Jeon, Choon-Ju;Kim, Hoeon
    • Molecules and Cells
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    • v.22 no.1
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    • pp.36-43
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    • 2006
  • Mesenchymal stem cells (MSCs) are promising candidates for cell therapy and tissue engineering, but their application has been impeded by lack of knowledge of their core biological properties. In order to identify MSC-specific proteins, the hydrophobic protein fraction was individually prepared from two different umbilical cord blood (UCB)-derived MSC populations; these were then subjected to two-dimensional (2D) gel electrophoresis and peptide mass fingerprinting matrix-assisted laser desorption/ionization (MALDI)-time of flight (TOF)-mass spectrometry (MS). Although the 2D gel patterns differed somewhat between the two samples, computer-assisted image analysis identified shared protein spots. 35 spots were reliably identified corresponding to 32 different proteins, many of which were chaperones. Based on their primary sub-cellular locations the proteins could be grouped into 6 categories: extracellular, cell surface, endoplasmic reticular, mitochondrial, cytoplasmic and cytoskeletal proteins. This map of the water-insoluble proteome may provide valuable insights into the biology of the cell surface and other compartments of human MSCs.

The Mitochondrial Warburg Effect: A Cancer Enigma

  • Kim, Hans H.;Joo, Hyun;Kim, Tae-Ho;Kim, Eui-Yong;Park, Seok-Ju;Park, Ji-Kyoung;Kim, Han-Jip
    • Interdisciplinary Bio Central
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    • v.1 no.2
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    • pp.7.1-7.7
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    • 2009
  • "To be, or not to be?" This question is not only Hamlet's agony but also the dilemma of mitochondria in a cancer cell. Cancer cells have a high glycolysis rate even in the presence of oxygen. This feature of cancer cells is known as the Warburg effect, named for the first scientist to observe it, Otto Warburg, who assumed that because of mitochondrial malfunction, cancer cells had to depend on anaerobic glycolysis to generate ATP. It was demonstrated, however, that cancer cells with intact mitochondria also showed evidence of the Warburg effect. Thus, an alternative explanation was proposed: the Warburg effect helps cancer cells harness additional ATP to meet the high energy demand required for their extraordinary growth while providing a basic building block of metabolites for their proliferation. A third view suggests that the Warburg effect is a defense mechanism, protecting cancer cells from the higher than usual oxidative environment in which they survive. Interestingly, the latter view does not conflict with the high-energy production view, as increased glucose metabolism enables cancer cells to produce larger amounts of both antioxidants to fight oxidative stress and ATP and metabolites for growth. The combination of these two different hypotheses may explain the Warburg effect, but critical questions at the mechanistic level remain to be explored. Cancer shows complex and multi-faceted behaviors. Previously, there has been no overall plan or systematic approach to integrate and interpret the complex signaling in cancer cells. A new paradigm of collaboration and a well-designed systemic approach will supply answers to fill the gaps in current cancer knowledge and will accelerate the discovery of the connections behind the Warburg mystery. An integrated understanding of cancer complexity and tumorigenesis is necessary to expand the frontiers of cancer cell biology.

Ginsenoside Rg3 ameliorates myocardial glucose metabolism and insulin resistance via activating the AMPK signaling pathway

  • Ni, Jingyu;Liu, Zhihao;Jiang, Miaomiao;Li, Lan;Deng, Jie;Wang, Xiaodan;Su, Jing;Zhu, Yan;He, Feng;Mao, Jingyuan;Gao, Xiumei;Fan, Guanwei
    • Journal of Ginseng Research
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    • v.46 no.2
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    • pp.235-247
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    • 2022
  • Background: Ginsenoside Rg3 is one of the main active ingredients in ginseng. Here, we aimed to confirm its protective effect on the heart function in transverse aortic coarctation (TAC)-induced heart failure mice and explore the potential molecular mechanisms involved. Methods: The effects of ginsenoside Rg3 on heart and mitochondrial function were investigated by treating TAC-induced heart failure in mice. The mechanism of ginsenoside Rg3 for improving heart and mitochondrial function in mice with heart failure was predicted through integrative analysis of the proteome and plasma metabolome. Glucose uptake and myocardial insulin sensitivity were evaluated using micro-positron emission tomography. The effect of ginsenoside Rg3 on myocardial insulin sensitivity was clarified by combining in vivo animal experiments and in vitro cell experiments. Results: Treatment of TAC-induced mouse models with ginsenoside Rg3 significantly improved heart function and protected mitochondrial structure and function. Fusion of metabolomics, proteomics, and targeted metabolomics data showed that Rg3 regulated the glycolysis process, and Rg3 not only regulated glucose uptake but also improve myocardial insulin resistance. The molecular mechanism of ginsenoside Rg3 regulation of glucose metabolism was determined by exploring the interaction pathways of AMPK, insulin resistance, and glucose metabolism. The effect of ginsenoside Rg3 on the promotion of glucose uptake in IR-H9c2 cells by AMPK activation was dependent on the insulin signaling pathway. Conclusions: Ginsenoside Rg3 modulates glucose metabolism and significantly ameliorates insulin resistance through activation of the AMPK pathway.

Proteomic analysis for the effects of non-saponin fraction with rich polysaccharide from Korean Red Ginseng on Alzheimer's disease in a mouse model

  • Sujin Kim;Yunkwon Nam;Min-jeong Kim;Seung-hyun Kwon;Junhyeok Jeon;Soo Jung Shin;Soyoon Park;Sungjae Chang;Hyun Uk Kim;Yong Yook Lee;Hak Su Kim;Minho Moon
    • Journal of Ginseng Research
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    • v.47 no.2
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    • pp.302-310
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    • 2023
  • Background: The most common type of dementia, Alzheimer's disease (AD), is marked by the formation of extracellular amyloid beta (Aβ) plaques. The impairments of axons and synapses appear in the process of Aβ plaques formation, and this damage could cause neurodegeneration. We previously reported that non-saponin fraction with rich polysaccharide (NFP) from Korean Red Ginseng (KRG) showed neuroprotective effects in AD. However, precise molecular mechanism of the therapeutic effects of NFP from KRG in AD still remains elusive. Methods: To investigate the therapeutic mechanisms of NFP from KRG on AD, we conducted proteomic analysis for frontal cortex from vehicle-treated wild-type, vehicle-treated 5XFAD mice, and NFP-treated 5XFAD mice by using nano-LC-ESI-MS/MS. Metabolic network analysis was additionally performed as the effects of NFP appeared to be associated with metabolism according to the proteome analysis. Results: Starting from 5,470 proteins, 2,636 proteins were selected for hierarchical clustering analysis, and finally 111 proteins were further selected for protein-protein interaction network analysis. A series of these analyses revealed that proteins associated with synapse and mitochondria might be linked to the therapeutic mechanism of NFP. Subsequent metabolic network analysis via genome-scale metabolic models that represent the three mouse groups showed that there were significant changes in metabolic fluxes of mitochondrial carnitine shuttle pathway and mitochondrial beta-oxidation of polyunsaturated fatty acids. Conclusion: Our results suggested that the therapeutic effects of NFP on AD were associated with synaptic- and mitochondrial-related pathways, and they provided targets for further rigorous studies on precise understanding of the molecular mechanism of NFP.

Identification of Heat Stress-related Proteins and Low Molecular Weight HSP Expressed in Stem Tissues of Rice Plants by Proteomic Analysis (프로테옴 분석법에 의한 벼 줄기에서 발현하는 고온 스트레스 관련 단백질 및 저분자량 Heat Shock Protein의 분리 동정)

  • Lee, Dong-Gi;Kim, Kyung-Hee;Kim, Yong-Gu;Lee, Ki-Won;Lee, Sang-Hoon;Lee, Byung-Hyun
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.31 no.2
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    • pp.99-106
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    • 2011
  • In order to investigate rice stem proteome in response to heat stress, rice plants were subjected to heat treatment at 42$^{\circ}C$ and total soluble proteins were extracted from stem tissues, and were fractionated with 15% PEG (poly ethylene glycol) and separated by two-dimensional polyacrylamide gel electrophoresis (2-DE). After staining of 2-DE gels, 46 of differentially expressed proteins were extracted, digested by trypsin, and subjected to matrix assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis. Proteins were identified through database search by using peptide mass fingerprints. Among them, 10 proteins were successfully identified. Seven proteins were up- and 3 proteins were down-regulated, respectively. These proteins are involved in energy and metabolism, redox homeostasis, and mitochondrial small heat shock proteins. The identification of some novel proteins in the heat stress response provides new insights that can lead to a better understanding of the molecular basis of heat-sensitivity in plants, and also useful to molecular breeding of thermotolerant forage crops.

Expression of Heat Shock Protein and Antioxidant Genes in Rice Leaf Under Heat Stress

  • Lee, Dong-Gi;Ahsan, Nagib;Kim, Yong-Goo;Kim, Kyung-Hee;Lee, Sang-Hoon;Lee, Ki-Won;Rahman, Md. Atikur;Lee, Byung-Hyun
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.33 no.3
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    • pp.159-166
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    • 2013
  • We have previously investigated the proteome changes of rice leaves under heat stress (Lee et al. in Proteomics 2007a, 7:3369-3383), wherein a group of antioxidant proteins and heat shock proteins (HSPs) were found to be regulated differently. The present study focuses on the biochemical changes and gene expression profiles of heat shock protein and antioxidant genes in rice leaves in response to heat stress ($42^{\circ}C$) during a wide range of exposure times. The results show that hydrogen peroxide and proline contents increased significantly, suggesting an oxidative burst and osmotic imbalance under heat stress. The mRNA levels of chaperone 60, HSP70, HSP100, chloroplastic HSP26, and mitochondrial small HSP responded rapidly and showed maximum expression after 0.5 or 2 h under heat stress. Transcript levels of ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR) and Cu-Zn superoxide dismutase (Cu-Zn SOD) showed a rapid and marked accumulation upon heat stress. While prolonged exposure to heat stress resulted in increased transcript levels of monodehydroascorbate reductase, peroxidase, glyoxalase 1, glutathione reductase, thioredoxin peroxidase, 2-Cysteine peroxiredoxin, and nucleoside diphosphate kinase 1, while the transcription of catalase was suppressed. Consistent with their changes in gene expression, the enzyme activities of APX and DHAR also increased significantly following exposure to heat stress. These results suggest that oxidative stress is usually caused by heat stress, and plants apply complex HSP- and antioxidant-mediated defense mechanisms to cope with heat stress.