• BMB Reports
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• v.41 no.12
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• pp.858-862
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• 2008

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a zinc-dependent proteinase found in cholesterol-rich lipid rafts on the plasma membrane. MT1-MMP hydrolyzes extracellular matrix (ECM) proteins, activates pro-matrix metalloproteinase-2 (proMMP-2) and plays an important role in ECM remodeling, cancer cell migration and metastasis. The role of caveolin-1, an integral protein of caveolae, in the activation of MT1-MMP remains largely unknown. Here, we show that the expression of caveolin-1 attenuates the activation of proMMP-2, reduces proteolytic cleavage of ECM and inhibits cell migration. We utilized the cytoplasmic tail domain deletion (${\Delta}CT$) or the E240A mutant of MT1-MMP. Co-expression of caveolin-1 with the wild-type or the ${\Delta}CT$ MT1-MMP decreased the proMMP-2 activation and inhibited collagen degradation and cell migration. Caveolin-1 had no effect on the catalytically inert E240A MT1-MMP. Our findings suggest that caveolin-1 is essential in the down-regulation of MT1-MMP activity by promoting internalization from the cell surface.

• International Journal of Oral Biology
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• v.43 no.1
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• pp.23-27
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• 2018

Increased intracellular levels of $Ca^{2+}$ are generally thought to negatively regulate lipolysis in mature adipocytes, whereas store-operated $Ca^{2+}$ entry was recently reported to facilitate lipolysis and attenuate lipotoxicity by inducing lipophagy. Transient receptor potential mucolipin1 (TRPML1), a $Ca^{2+}$-permeable non-selective cation channel, is mainly expressed on the lysosomal membrane and plays key roles in lysosomal homeostasis and membrane trafficking. However, the roles of TRPML1 in lipolysis remains unclear. In this study, we examined whether the channel function of TRPML1 induces lipolysis in mature adipocytes. We found that treatment of mature adipocytes with ML-SA1, a specific agonist of TRPML1, solely upregulated extracellular glycerol release, but not to the same extent as isoproterenol. In addition, knockdown of TRPML1 in mature adipocytes significantly reduced autophagic flux, regardless of ML-SA1 treatment. Our findings demonstrate that the channel function of TRPML1 partially contributes to lipid metabolism and autophagic membrane trafficking, suggesting that TRPML1, particularly the channel function of TRPML1, is as therapeutic target molecule for treating obesity.

• Natural Product Sciences
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• v.13 no.2
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• pp.118-122
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• 2007

We have studied the cytoprotective effect on H$_2$O$_2$ induced oxidative stress from leaves of Carpinus tschonoskii. The methanol extract of Carpinus tschonoskii was found to scavenge intracellular reactive oxygen species (ROS) using flow cytometry and confocal microscope. This extract prevented lipid peroxidation and thus reduced cell death of Chinese hamster lung fibroblast (V79-4) induced by H$_2$O$_2$ treatment. The extract increased catalase activity and phosphorylation of extracellular signal regulated kinase (ERK). Taken together, the results suggest that Carpinus tschonoskii protects V79-4 cells against oxidative damage by H$_2$O$_2$ through scavenging ROS.

• Investigative Magnetic Resonance Imaging
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• v.13 no.1
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• pp.81-87
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• 2009

Purpose : We sought to evaluate enhancement of plaque with gadolinium-based contrast agent by magnetic resonance imaging (MRI) in comparison with histopathology, namely lipid-rich and macrophage-rich components that were two representative characteristics of plaque vulnerability using atherosclerotic rabbit aorta in order to determine which histopathologic component is relevant to the enhancement. Materials and Methods : New Zealand white rabbit (n=4, weight 3.0 to 3.5 kg, all male) was used for animal model of atherosclerosis. Atherosclerotic aortic lesions were induced by high-cholesterol diet and double balloon injury. T1-weight axial images were acquired before and after gadolinium-based contrast agent using a 3-T MRI. MR images and the matched histopathological sections (n=35) were divided into 4 quadrants or 3 (n=130). Enhancement ratio (ER, ER=SIpost/SIpre) on MRI was calculated for each quadrant and compared with histopathology in regard to lipid-rich and macrophage-rich areas. Results : Lipid-rich quadrants were 72 and fibrous quadrants were 58. The number of quadrants which had macrophage-rich areas was 105 and that of quadrants which did not have macrophage-rich areas was 25. ER was significantly higher in lipid-rich quadrants than in fibrous quadrants (mean ER 2.25c$\pm$0.41 vs. 2.72$\pm$0.65, p=0.013). ER poorly correlated with macrophage-rich areas when lipid-component was controlled (correlation coefficient -0.203, p=0.236). Conclusion : Lipid-rich plaques showed stronger enhancement than fibrous plaques using a standard gadolinium-based extracellular contrast agent. Macrophage infiltration did not correlate with degree of enhancement. Further study is warranted that account for optimal time of imaging after contrast injection using various plaque models from early to advanced stages and all possible parameters associated with contrast enhancement.

• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.85-92
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• 2020

One of the omega-3 essential fatty acids, docosahexaenoic acid (DHA), is a significant constituent of the cell membrane and the precursor of several potent lipid mediators. These mediators are considered to be important in preventing or treating several diseases. Resolvin D5, an oxidized lipid mediator derived from DHA, has been known to exert anti-inflammatory effects. However, the detailed mechanism underlying these effects has not yet been elucidated in human monocytic THP-1 cells. In the present study, we investigated the effects of resolvin D5 on inflammation-related signaling pathways, including the extracellular signal-regulated kinase (ERK)-nuclear factor (NF)-κB signaling pathway. Resolvin D5 downregulated the production of interleukin (IL)-6 and chemokine (C-C motif) ligand 5 (CCL5). Additionally, these inhibitory effects were found to be modulated by mitogen-activated protein kinase (MAPK) and NF-κB in lipopolysaccharide (LPS)-treated THP-1 cells. Resolvin D5 inhibited the LPS-stimulated phosphorylation of ERK and translocation of p65 and p50 into the nucleus, resulting in the inhibition of IL-6 and CCL5 production. These results revealed that resolvin D5 exerts anti-inflammatory effects in LPS-treated THP-1 cells by regulating the phosphorylation of ERK and nuclear translocation of NF-κB.

• Journal of Ginseng Research
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• v.41 no.1
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• pp.23-30
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• 2017

Background: Ginsenoside Rg1 is a class of steroid glycoside and triterpene saponin in Panax ginseng. Many studies suggest that Rg1 suppresses adipocyte differentiation in 3T3-L1. However, the detail molecular mechanism of Rg1 on adipogenesis in 3T3-L1 is still not fully understood. Methods: 3T3-L1 preadipocyte was used to evaluate the effect of Rg1 on adipocyte development in the differentiation in a stage-dependent manner in vitro. Oil Red O staining and Nile red staining were conducted to measure intracellular lipid accumulation and superoxide production, respectively. We analyzed the protein expression using Western blot in vitro. The zebrafish model was used to investigate whether Rg1 suppresses the early stage of fat accumulation in vivo. Results: Rg1 decreased lipid accumulation in early-stage differentiation of 3T3-L1 compared with intermediate and later stages of adipocyte differentiation. Rg1 dramatically increased CAAT/enhancer binding protein (C/EBP) homologous protein-10 (CHOP10) and subsequently reduced the $C/EBP{\beta}$ transcriptional activity that prohibited the initiation of adipogenic marker expression as well as triglyceride synthase. Rg1 decreased the expression of extracellular signal-regulated kinase 1/2 and glycogen synthase kinase $3{\beta}$, which are also essential for stimulating the expression of $CEBP{\beta}$. Rg1 also reduced reactive oxygen species production because of the downregulated protein level of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase 4 (NOX4). While Rg1 increased the endogenous antioxidant enzymes, it also dramatically decreased the accumulation of lipid and triglyceride in high fat diet-induced obese zebrafish. Conclusion: We demonstrated that Rg1 suppresses early-stage differentiation via the activation of CHOP10 and attenuates fat accumulation in vivo. These results indicate that Rg1 might have the potential to reduce body fat accumulation in the early stage of obesity.

• Journal of Life Science
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• v.32 no.3
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• pp.256-262
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• 2022

Oxysterols are oxygenated metabolites of cholesterol generated by serial enzymatic reactions during bile acid synthesis. Similar to cholesterol, oxysterols move rapidly to the intracellular region and modulate various cellular processes, such as immune cell responses, lipid metabolism, and cholesterol homeostasis. Different nuclear transcription factors, such as glucocorticoid, estrogen, and liver X receptors, can be modulated by oxysterols in multiple tissues. The most abundant oxysterol, 27-hydroxycholesterol (27-OHC), is a well-known selective modulator that can either activate or suppress estrogen receptor activity in a tissue-specific manner. The contribution of 27-OHC in atherosclerosis development is apparent because a large amount of it is found in atherosclerotic plaques, accelerating the transformation of macrophages into foam cells that uptake extracellular modified lipids. According to previous studies, however, there are opposing opinions about how 27-OHC affects lipid and cholesterol metabolism in metabolic organs, including the liver and adipose tissue. In particular, the effects of 27-OHC on lipid metabolism are entirely different between in vitro and in vivo conditions, suggesting that understanding the physiology of this oxysterol requires a sophisticated approach. This review summarizes the potential effects of 27-OHC in atherosclerosis and metabolic syndromes with a special discussion of its role in metabolic tissues.

• The Korean Journal of Medicine
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• v.93 no.6
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• pp.548-555
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• 2018

Background/Aims: Assessment of fluid status in hemodialysis patents is very important. Overhydration in hemodialysis is associated with generalized edema, cardiovascular complications, and hypertension. The aim of this study was to determine the factors correlated with mortality of hemodialysis patients, assessing body muscle mass and fluid status using bioelectrical impedance analysis (BIA). Methods: This study enrolled 93 patients who underwent hemodialysis between January 2010 and May 2015 at CHA Bundang Medical Center. Medical records of enrollees up to June 2017 were reviewed retrospectively. These included laboratory results (serum albumin, C-reactive protein [CRP], lipid profile, etc.) and BIA data (extracellular water, intracellular water, total body water, soft lean mass, fat free mass, skeletal muscle mass, etc.). Results: Eleven of 93 patients had expired by May 2017. Among the surviving subjects, mean age was younger, CRP levels were lower, albumin levels were higher, and extracellular water/total body water (ECW/TBW) ratios were lower than in the expired patient group. Kaplan-Meier survival analysis revealed that overhydration (ECW/TBW > 0.4) was associated with higher mortality. Conclusions: In hemodialysis patients, overhydration is an important factor in mortality, and BIA could be a reliable modality in its assessment. We suggest that, for hemodialysis patients, overhydration is more of a risk factor for mortality than is muscle wasting.

• Korean Journal of Exercise Nutrition
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• v.13 no.1
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• pp.15-21
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• 2009

Ergogenic aids are substances, devices, and practices that enhance an individual's energy use and production, and recovery from fatigue. L-carnitine increases enhance performance and aerobic capacity by stimulating lipid oxidation in muscle cells during long term exercise. L-carnitine is a well known and widely used ergogenic aid. In the present study, the effect of L-carnitine at concentrations of 100 nM, 1 μM, 10 μM, and 100 μM on the amplitude of field potential in rat cardiac muscle slices was measured using multi-channel extracellular recording (MED 64) system. In the present result, L-carnitine was shown to enhance field potential as a does-dependent manner. The increasing effect of the L-carnitine on field potential was not affected by application of the glibenclamide, an ATP-dependant K⁺ channel antagonist. The increasing effect of L-carnitine on field potential was suppressed by application of the diazoxide, an ATP-dependent K⁺ channel agonist. Present data show that L-carnitine potentiates field potentials by inhibition on ATP-dependant K⁺ channel in cardiac muscles. The enhancing effect of the L-carnitine on the field potential in cardiac muscles can be suggested as one of the underlying mechanism of ergogenic aid of the L-carnitine.

• IMMUNE NETWORK
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• v.16 no.5
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• pp.296-304
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• 2016

It has been reported that fatty acid binding proteins (FABPs) do not act only as intracellular mediators of lipid responses but also have extracellular functions. This study aimed to investigate whether extracellular liver type (L)-FABP has a biological activity and to determined serum L-FABP levels in patients with end-stage renal disease (ESRD). We isolated L-FABP complementary deoxyribonucleic acid (cDNA) from the Huh7 human hepatocarcinoma cell line and expressed the recombinant L-FABP protein in Escherichia coli. A549 lung carcinoma and THP-1 monocytic cells were stimulated with the human recombinant L-FABP. Human whole blood cells were also treated with the human recombinant L-FABP or interleukin (IL)-1α. IL-6 levels were measured in cell culture supernatants using IL-6 enzyme-linked immunosorbent assay (ELISA). Human recombinant L-FABP induced IL-6 in a dose-dependent manner in A549, THP-1 cells, and whole blood cells. The blood samples of healthy volunteers and patients with ESRD were taken after an overnight fast. The serum levels of L-FABP in healthy volunteers and ESRD patients were quantified with L-FABP ELISA. The values of L-FABP in patients with ESRD were significantly lower than those in the control group. Our results demonstrated the biological activity of L-FABP in human cells suggesting L-FABP can be a mediator of inflammation.