• Title/Summary/Keyword: Metabolism regulation

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Actin-binding LIM protein 1 regulates receptor activator of NF-κB ligand-mediated osteoclast differentiation and motility

  • Jin, Su Hyun;Kim, Hyunsoo;Gu, Dong Ryun;Park, Keun Ha;Lee, Young Rae;Choi, Yongwon;Lee, Seoung Hoon
    • BMB Reports
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    • v.51 no.7
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    • pp.356-361
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    • 2018
  • Actin-binding LIM protein 1 (ABLIM1), a member of the LIM-domain protein family, mediates interactions between actin filaments and cytoplasmic targets. However, the role of ABLIM1 in osteoclast and bone metabolism has not been reported. In the present study, we investigated the role of ABLIM1 in the receptor activator of $NF-{\kappa}B$ ligand (RANKL)-mediated osteoclastogenesis. ABLIM1 expression was induced by RANKL treatment and knockdown of ABLIM1 by retrovirus infection containing Ablim1-specific short hairpin RNA (shAblim1) decreased mature osteoclast formation and bone resorption activity in a RANKL-dose dependent manner. Coincident with the downregulated expression of osteoclast differentiation marker genes, the expression levels of c-Fos and the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), critical transcription factors of osteoclastogenesis, were also decreased in shAblim1-infected osteoclasts during RANKL-mediated osteoclast differentiation. In addition, the motility of preosteoclast was reduced by ABLIM1 knockdown via modulation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt/Rac1 signaling pathway, suggesting another regulatory mechanism of ABLIM1 in osteoclast formation. These data demonstrated that ABLIM1 is a positive regulator of RANKL-mediated osteoclast formation via the modulation of the differentiation and PI3K/Akt/Rac1-dependent motility.

Single-cell RNA sequencing reveals the heterogeneity of adipose tissue-derived mesenchymal stem cells under chondrogenic induction

  • Jeewan Chun;Ji-Hoi Moon;Kyu Hwan Kwack;Eun-Young Jang;Saebyeol Lee;Hak Kyun Kim;Jae-Hyung Lee
    • BMB Reports
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    • v.57 no.5
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    • pp.232-237
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    • 2024
  • This study investigated how adipose tissue-derived mesenchymal stem cells (AT-MSCs) respond to chondrogenic induction using droplet-based single-cell RNA sequencing (scRNA-seq). We analyzed 37,219 high-quality transcripts from control cells and cells induced for 1 week (1W) and 2 weeks (2W). Four distinct cell clusters (0-3), undetectable by bulk analysis, exhibited varying proportions. Cluster 1 dominated in control and 1W cells, whereas clusters (3, 2, and 0) exclusively dominated in control, 1W, and 2W cells, respectively. Furthermore, heterogeneous chondrogenic markers expression within clusters emerged. Gene ontology (GO) enrichment analysis of differentially expressed genes unveiled cluster-specific variations in key biological processes (BP): (1) Cluster 1 exhibited up-regulation of GO-BP terms related to ribosome biogenesis and translational control, crucial for maintaining stem cell properties and homeostasis; (2) Additionally, cluster 1 showed up-regulation of GO-BP terms associated with mitochondrial oxidative metabolism; (3) Cluster 3 displayed up-regulation of GO-BP terms related to cell proliferation; (4) Clusters 0 and 2 demonstrated similar up-regulation of GO-BP terms linked to collagen fibril organization and supramolecular fiber organization. However, only cluster 0 showed a significant decrease in GO-BP terms related to ribosome production, implying a potential correlation between ribosome regulation and the differentiation stages of AT-MSCs. Overall, our findings highlight heterogeneous cell clusters with varying balances between proliferation and differentiation before, and after, chondrogenic stimulation. This provides enhanced insights into the single-cell dynamics of AT-MSCs during chondrogenic differentiation.

The Effects of a High-fat or High-sucrose Diet on Serum Lipid Profiles, Hepatic Acyl-CoA Synthetase, Carnitine Palmitoyltransferase-I, and the Acetyl-CoA Carboxylase mRNA Levels in Rats

  • Ryu, Mi-Hyun;Cha, Youn-Soo
    • BMB Reports
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    • v.36 no.3
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    • pp.312-318
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    • 2003
  • The purpose of this study was to investigate the effects of altering relative intakes of fat and carbohydrates on serum lipid profiles, hepatic acyl-CoA synthetase (ACS), carnitine palmitoyltransferase-I (CPT-I), and the acetyl-CoA carboxlyase (ACC) mRNA level in Sprague-Dawley rats. For four weeks the rats were fed either an AIN-76 diet or one of its modified diets that were supplemented with 20% beef tallow (high-fat diet, HF) and 66.3% sucrose (highsucrose diet, HS). The HS group had significantly higher serum triglyceride and total cholesterol concentrations when compared with the other groups. Serum LDL-cholesterol concentrations in the HS and HF groups were significantly higher when compared to the normal diet (ND) group. Serum HDL-cholesterol levels of the ND and HS groups were significantly higher than those of the HF group. The hepatic total lipid level of the HF group was significantly higher than those of other groups; triglyceride levels of the HS and HF groups were significantly higher than those of the ND group. Hepatic ACS mRNA levels of the HF group were significantly higher than those of the ND group. Hepatic CPT-I mRNA levels were higher in the HF group than other groups. Also, ACC mRNA levels in the liver increased in the HF group. In conclusion, changes in the composition of dietary fat and carbohydrates could affect the hepatic ACS, CPT-I, and ACC mRNA levels. These results facilitate our understanding of the coordinated regulation of the ACS, CPT-I, and ACC mRNA levels and will serve to enhance our understanding of the molecular mechanisms that underlie the regulation of fatty acid metabolism.

Regulation of Sulfur Metabolism in Cephalosporium acremonium (Cephalosporium acremonium에서 황화합물 대사의 조절)

  • Lee, Kyoung;Park, Sang-Ho;Lee, Jung-Joon;Mheen, Tae-Ick
    • Microbiology and Biotechnology Letters
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    • v.15 no.5
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    • pp.361-367
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    • 1987
  • A DL-seleno-methionine resistant mutant, Cephalosporium acremonium MS-92 showed increased activities of sulfate and L-methionine uptake than the parent strain, and accumulated excess methionine and S-adenosylmethionine (SAM) intracellularly. And the sulfate uptake system was severely inhibited by L-cysteine. In crude enzyme extracts, the mutant MS-92 showed lower L-serine sulfhydrylase (identical with cystathionine $\beta$-synthase) activity than the parent. Also, cysteine desulfhydrylase activity, an index of intracellular L-cysteine concentration, of the mutant MS-92 was decreased by about 50% as com-pared with that of the parent. Thus, it was supposed that the mutant MS-92 should have n lower level of L-cysteine than the parent. In C. acremonium like A. nidulans, the enzymes related to the biosynthesis of methionine might be regulated by L-cysteine, but not by methionine or SAM.

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Effect of Pioglitazone on Perihematomal Edema in Intracerebral Hemorrhage Mouse Model by Regulating NLRP3 Expression and Energy Metabolism

  • Kim, Hoon;Lee, Jung Eun;Yoo, Hyun Ju;Sung, Jae Hoon;Yang, Seung Ho
    • Journal of Korean Neurosurgical Society
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    • v.63 no.6
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    • pp.689-697
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    • 2020
  • Objective : Cerebral edema is the predominant mechanism of secondary inflammation after intracerebral hemorrhage (ICH). Pioglitazone, peroxisome proliferator-activated receptor gamma agonist has been shown to play a role in regulation of central nervous system inflammation. Here, we examined the pharmacological effects of pioglitazone in an ICH mouse model and investigated its regulation on NLRP3 inflammasome and glucose metabolism. Methods : The ICH model was established in C57 BL/6 mice by the stereotactical inoculation of blood (30 µL) into the right frontal lobe. The treatment group was administered i.p. pioglitazone (20 mg/kg) for 1, 3, and 6 days. The control group was administered i.p. phosphate-buffered saline for 1, 3, and 6 days. We investigated brain water contents, NLRP3 expression, and changes in the metabolites in the ICH model using liquid chromatography-tandem mass spectrometry. Results : On day 3, brain edema in the mice treated with pioglitazone was decreased more than that in the control group. Expression levels of NLRP3 in the ICH model treated with pioglitazone were decreased more than those of the control mice on days 3 and 7. The pioglitazone group showed higher levels of glycolytic metabolites than those in the ICH mice. Lactate production was increased in the ICH mice treated with pioglitazone. Conclusion : Our results demonstrated less brain swelling following ICH in mice treated with pioglitazone. Pioglitazone decreased NLRP3-related brain edema and increased anaerobic glycolysis, resulting in the production of lactate in the ICH mice model. NLRP3 might be a therapeutic target for ICH recovery.

Expressional Analysis of Two Genes (Scd1 and Idi1) Down-regulated by Starvation Stress (영양고갈-스트레스에 의해서 하강발현하는 유전자(Scd1과 Idi1)의 분석)

  • Cho, Junho;Kwon, Young-Sook;Kim, Dong-Il;Kim, Bok Jo;Kwon, Kisang
    • Journal of Life Science
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    • v.24 no.7
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    • pp.762-768
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    • 2014
  • Diet exerts a major stress on the body and may affect gene expression and physiological functions. Understanding of cellular responses during starvation is necessary in developing strategies to reduce damage caused by diet. In this study, we isolated 10 genes (Comt, RGN, Scd1, Temt, Idi1, Fabp5, Car3, Cyp2c70, Pinx1, and Poldip3) that are down-regulated in starvation and are closely related to liver metabolism. Water supply during starvation had no effect on the induction of apoptosis, autophagy, and ERQC. The genes down-regulated by starvation were associated with many related pathways rather than limited to the liver homeostasis pathway. Water supply during starvation is important. However, maintaining NaCl homeostasis is more important. The results are thought to be closely related to gender-specific metabolism in starvation and NaCl.

Proteome-based Identification of Proteins Regulated by Aldosterone in Rat Kidney Cortex (프로테오믹스 기술을 통한 쥐의 신장 피질에서 알도스테론(Aldosterone)에 의해 조절되는 단백질 동정)

  • Song, Mi-Na;Jeon, Hong-Bae;Choi, Hyo-Jung;Kwon, Tae-Hwan;Baek, Moon-Chang
    • YAKHAK HOEJI
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    • v.54 no.3
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    • pp.180-186
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    • 2010
  • Aldosterone, mineralocorticoid hormone, has important functions related to the regulation of blood pressure and balance of fluids and electrolytes in the distal region of the nephron. By genomic and non-genomic action of aldosterone, the physiological kidney functions are modulated. However, many of them except several kind of sodium channel have not been identified and analyzed yet. In this study, proteomic technologies with two-dimensional gel electrophoresis (2-DE) gel using aldosterone rat model were applied to analyze and identify the aldosterone dependently expressed proteins in rat kidney cortex. As a result, the established aldosterone rat model exhibited the normal physiological responses to aldosterone and modulated proteins were identified, which included 15 increased and 3 decreased proteins on 2-DE analysis. Among them, 11 proteins were identified as changed proteins by LC-MS/MS analysis. These proteins identified as aldosterone induced proteins were involved in several cellular pathways such as cytoskeleton remodeling, energy metabolism, amino acid metabolism, and chaperone process. In conclusion, our data could provide the insights into the new mechanism underlying regulation of kidney functions by aldosterone.

Effect of White, Taegeuk, and Red Ginseng Root Extracts on Insulin-Stimulated Glucose Uptake in Muscle Cells and Proliferation of β-cells

  • Cha, Ji-Young;Park, Eun-Young;Kim, Ha-Jung;Park, Sang-Un;Nam, Ki-Yeul;Choi, Jae-Eul;Jun, Hee-Sook
    • Journal of Ginseng Research
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    • v.34 no.3
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    • pp.192-197
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    • 2010
  • Recent studies have indicated that $\beta$-cell dysfunction and insulin resistance are important factors in the development of type 2 diabetes. The present study investigated the effect of extracts from different parts of white, Taegeuk, and red ginseng root on insulin-stimulated glucose uptake in muscle cells and proliferation of $\beta$-cells. Extracts of the fine roots of Taegeuk ginseng significantly enhanced glucose uptake compared with the control. White ginseng lateral root extracts enhanced insulin-induced glucose uptake. Proliferation of $\beta$-cells was significantly increased by Taegeuk ginseng main and lateral root extracts and by red ginseng lateral and fine root extracts. In conclusion, different root parts of white, Taegeuk, and red ginseng differentially affect glucose uptake and pancreatic $\beta$-cell proliferation.

Health Improvement and Treatment Effect of Probiotics (프로바이오틱스의 건강증진과 질병치료 효능)

  • Baek, Young-Mi;Kim, Kyung-Soon;Lee, Yeon-Weol;Cho, Chong-Kwan;Yoo, Hwa-Seung
    • Journal of Haehwa Medicine
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    • v.19 no.1
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    • pp.25-34
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    • 2010
  • Background : The human being and the bacteria have accomplished a balance and have coexisted each other during long time. Probiotics have evolved with the human host to exist and the result they have operated profitably to human host. So it requires that the functions of probiotics are expounded in view of Traditional Korean Medicine. Aim : Suggest the functions of probiotics in view of Traditional Korean Medicine. Method : The author's research has been performed to review the related references. Results : Probiotics assist the absorption of the lactose, proteins and minerals and product several kinds of vitamins, organic acids. Probiotics suppresses the growth of noxious bacteria and the production of harmful substances or gases. They absorbed and discharge the bile acid, and thus help us maintain the optimal level of blood cholesterol concentration. They can reinforce the immune response of the mucous membrane and control the hypersensitivity immune reaction such as asthma, atopy on the other hand. Probiotics have right functions as above and so can be applied widely in treatment of various disease and symptom. Conclusion : Considering the functions of probiotics in view of Traditional Korean Medicine, they participate in our spleen-earth-system (digestion and synthesis) and liver-wood-system (regulation of digestion, metabolism, internal secretion etc.), assist the function of lung-metal system(respiration and regulation of water metabolism) and regulate wi-chi (reinforce/control immune system). Consequently, hereafter there would be a necessity of control a circumstance in treatment of various diseases under these categories that probiotics should be able to do their right functions inside the human body.

The Regulation of LexA on UV-Induced SOS Response in Myxococcus xanthus Based on Transcriptome Analysis

  • Sheng, Duo-hong;Wang, Ye;Wu, Shu-ge;Duan, Rui-qin;Li, Yue-zhong
    • Journal of Microbiology and Biotechnology
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    • v.31 no.7
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    • pp.912-920
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    • 2021
  • SOS response is a conserved response to DNA damage in prokaryotes and is negatively regulated by LexA protein, which recognizes specifically an "SOS-box" motif present in the promoter region of SOS genes. Myxococcus xanthus DK1622 possesses a lexA gene, and while the deletion of lexA had no significant effect on either bacterial morphology, UV-C resistance, or sporulation, it did delay growth. UV-C radiation resulted in 651 upregulated genes in M. xanthus, including the typical SOS genes lexA, recA, uvrA, recN and so on, mostly enriched in the pathways of DNA replication and repair, secondary metabolism, and signal transduction. The UV-irradiated lexA mutant also showed the induced expression of SOS genes and these SOS genes enriched into a similar pathway profile to that of wild-type strain. Without irradiation treatment, the absence of LexA enhanced the expression of 122 genes that were not enriched in any pathway. Further analysis of the promoter sequence revealed that in the 122 genes, only the promoters of recA2, lexA and an operon composed of three genes (pafB, pafC and cyaA) had SOS box sequence to which the LexA protein is bound directly. These results update our current understanding of SOS response in M. xanthus and show that UV induces more genes involved in secondary metabolism and signal transduction in addition to DNA replication and repair; and while the canonical LexA-dependent regulation on SOS response has shrunk, only 5 SOS genes are directly repressed by LexA.