Park, Jong-Gil;Jeong, Se-Jin;Yu, Jinha;Kim, Gyudong;Jeong, Lak Shin;Oh, Goo Taeg
BMB Reports
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제51권10호
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pp.520-525
/
2018
Cardiovascular diseases arising from atherosclerosis are the leading causes of mortality and morbidity worldwide. Lipid-lowering agents have been developed in order to treat hypercholesterolemia, a major risk factor for atherosclerosis. However, the prevalence of cardiovascular diseases is increasing, indicating a need to identify novel therapeutic targets and develop new treatment agents. Adenosine receptors (ARs) are emerging as therapeutic targets in asthma, rheumatoid arthritis, cancer, ischemia, and inflammatory diseases. This study assessed whether LJ-1888, a selective antagonist for $A_3$ AR, can inhibit the development of atherosclerosis in apolipoprotein E knock-out ($ApoE^{-/-}$) mice who are fed a western diet. Plaque formation was significantly lower in $ApoE^{-/-}$ mice administered LJ-1888 than in mice not administered LJ-1888, without any associated liver damage. LJ-1888 treatment of $ApoE^{-/-}$ mice prevented western diet-induced hypercholesterolemia by markedly reducing low-density lipoprotein cholesterol levels and significantly increasing high-density lipoprotein cholesterol concentrations. Reduced hypercholesterolemia in $ApoE^{-/-}$ mice administered LJ-1888 was associated with the enhanced expression of genes involved in bile acid biosynthesis. These findings indicate that LJ-1888, a selective antagonist for $A_3$ AR, may be a novel candidate for the treatment of atherosclerosis and hypercholesterolemia.
Tang, Wenwen;Yuan, Jian;Chen, Xinya;Gu, Xiuting;Luo, Kuntian;Li, Jie;Wan, Bo;Wang, Yingli;Yu, Long
BMB Reports
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제39권5호
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pp.626-635
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2006
Lysophosphatidic acid acyltransferase (LPAAT) is an intrinsic membrane protein that catalyzes the synthesis of phosphatidic acid (PA) from lysophosphatidic acid (LPA). It is well known that LPAAT is involved in lipid biosynthesis, while its role in tumour progression has been of emerging interest in the last few years. To date, seven members of the LPAAT gene family have been found in human. Here we report a novel LPAAT member, designated as LPAAT-theta, which was 2728 base pairs in length and contained an open reading frame (ORF) encoding 434 amino acids. The LPAAT-theta gene consisted of 12 exons and 11 introns, and mapped to chromosome 4q21.23. LPAAT-theta was ubiquitously expressed in 18 human tissues by RT-PCR analysis. Subcellular localization of LPAAT-theta-EGFP fusion protein revealed that LPAAT-theta was distributed primarily in the endoplasmic reticulum (ER) of COS-7 cells. Furthermore, we found that the overexpression of LPAAT-theta can induce mTOR-dependent p70S6K phosphorylation on Thr389 and 4EBP1 phosphorylation on Ser65 in HEK293T cells.
This study was conducted to determine the effects of saturated long-chain fatty acids (LCFA) on cell proliferation and triacylglycerol (TAG) content, as well as mRNA expression of ${\alpha}s1$-casein (CSN1S1) and genes associated with lipid and protein synthesis in bovine mammary epithelial cells (BMECs). Primary cells were isolated from the mammary glands of Holstein dairy cows, and were passaged twice. Then cells were cultured with different levels of palmitate or stearate (0, 200, 300, 400, 500, and 600 ${\mu}M$) for 48 h and fetal bovine serum in the culture solution was replaced with fatty acid-free BSA (1 g/L). The results showed that cell proliferation tended to be increased quadratically with increasing addition of stearate. Treatments with palmitate or stearate induced an increase in TAG contents at 0 to 600 ${\mu}M$ in a concentration-dependent manner, and the addition of 600 ${\mu}M$ was less effective in improving TAG accumulation. The expression of acetyl-coenzyme A carboxylase alpha, fatty acid synthase and fatty acid-binding protein 3 was inhibited when palmitate or stearate were added in culture medium, whereas cluster of differentiation 36 and CSN1S1 mRNA abundance was increased in a concentration-dependent manner. The mRNA expressions of peroxisome proliferator-activated receptor gamma, mammalian target of rapamycin and signal transducer and activator of transcription 5 with palmitate or stearate had no significant differences relative to the control. These results implied that certain concentrations of saturated LCFA could stimulate cell proliferation and the accumulation of TAG, whereas a reduction may occur with the addition of an overdose of saturated LCFA. Saturated LCFA could up-regulate CSN1S1 mRNA abundance, but further studies are necessary to elucidate the mechanism for regulating milk fat and protein synthesis.
A 12-wk feeding trial was conducted to evaluate the essentiality of choline supplementation in diets for parrot fish. Five isonitrogenous and isocaloric diets were supplemented with 0 (as control), 500, 1,000, and 2,000 mg choline per kg diet, and a positive control diet without choline contained 0.3% of 2-amino-2-methyl-1-propanol as choline biosynthesis inhibitor (designated as Con, C500, C1000, C2000 and $Con^+$, respectively). Triplicate groups of fish (body weight, $8.8{\pm}0.01g$) were fed one of the experimental diets at a rate of 4% body weight twice daily. The fish fed $Con^+$ diet revealed significantly lower growth performance and feed utilization efficiency than other fish groups. Supplementation of choline to the basal diet did not significantly influence fish growth. The highest liver lipid content was observed in fish fed the $Con^+$ diet and inversely correlated with liver choline concentration although the differences were not significant. Also, significantly higher liver linoleic, eicosapentaenoic and docosahexaenoic acid contents were found in fish fed the $Con^+$ diet. Innate immune parameters including respiratory burst and myeloperoxidase activities were not significantly affected by dietary choline levels. The findings in this study conclude that choline concentration of approximately $230mgkg^{-1}$ diet meets the requirement of parrot fish.
The difference in the breeding programs and population history may have diversely shaped the genomes of Korean native cattle breeds. In the absence of phenotypic data, comparisons of breeds that have been subjected to different selective pressures can aid to identify genomic regions and genes controlling qualitative and complex traits. In this study to decipher genetic variation and identify evidence of divergent selection, 3 Korean cattle breeds were genotyped using the recently developed high-density GeneSeek Genomic Profiler F250 (GGP-F250) array. The three Korean cattle breeds clustered according to their coat color phenotypes and breeding programs. The Heugu breed reliably showed smaller effective population size at all generations considered. Across the autosomal chromosomes, 113 and 83 annotated genes were identified from Hanwoo-Chikso and Hanwoo-Heugu comparisons, respectively of which 16 genes were shared between the two pairwise comparisons. The most important signals of selection were detected on bovine chromosomes 14 (24.39-25.13 Mb) and 18 (13.34-15.07 Mb), containing genes related to body size, and coat color (XKR4, LYN, PLAG1, SDR16C5, TMEM68, CDH15, MC1R, and GALNS). Some of the candidate genes are also associated with meat quality traits (ACSF3, EIF2B1, BANP, APCDD1, and GALM) and harbor quantitative trait locus (QTL) for beef production traits. Further functional analysis revealed that the candidate genes (DBI, ACSF3, HINT2, GBA2, AGPAT5, SCAP, ELP6, APOB, and RBL1) were involved in gene ontology (GO) terms relevant to meat quality including fatty acid oxidation, biosynthesis, and lipid storage. Candidate genes previously known to affect beef production and quality traits could be used in the beef cattle selection strategies.
Objectives: Schizandrae fructus (Schizandra chinensis) is one of very common herbs, it is known as natural antioxidants, anti-inflammatory agent. Also some reports show that its extract works to regulate of dyslipidemia. This study was designed to investigate the effects of Schizandrae fructus chloroform fraction (SFCF) on serum lipid levels in dyslipidemic mice. Methods: The levels of total cholesterol, high density lipoprotein-cholesterol, triglyceride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting blood glucose in serum were measured. Histopathological and gene expression changes in liver tissue were also observed. Results: Oral administration of SFCF lowered levels of total cholesterol and triglyceride, which were elevated by high-fat diet. But SFCF did not affect on weight changes and serum AST, ALT levels in dyslipidemic mice. After carrying out gene ontological analysis, large numbers of genes in high-fat diet group were up-(347) or down-regulated (235). In SFCF treated mice, some changed expression of the genes was restored to normal levels, with a recovery rate of 17%. And it seems that fatty acid biosynthesis pathway was one of important key pathways to recovery. Conclusions: SFCF has beneficial effect on dyslipidemia, and could be used to prevent and treat cardiovascular disease.
In the process of the incorporation of orthophsphate into protein and other cell constituents, the role of inorganic polyphosphate and RNA-polyphosphate complex and the correlation between them were pursued by analyzing the contents of $^{32}P$ and total P in various fractions of Chlorella cells, which had been uniformly labeled with $^{32}P$ before the inoculation in a normal "cold" medium or P-free medium during the culture. The effects of ionizing radiation and various micronutritional-element deficiencies on the phosphate incorporation into, and biosynthesis of, protein and other introgenus compounds in the cells were also observed. When the uniformly $^{32}P$-labeled algae were grown in a normal "cold" medium the contents of $^{32}$ P in the fractions of protein, DNA and RNA-polyphosphate complex increased, but those in the fraction of acid-insoluble polyphosphate decreased. On the other hand, amount of $^{32}P$in the fraction of RNA was almost unchanged in spite of rapid increase of the total P. In the growing period of $^{32}P$-labeled algae in a P-free medium, amounts of $^{32}P$ in the fractions of DNA, protein and lipid increased, while those in the fractions of RNA-polyphosphate and inorganic polyphosphates decreased. When the algal cells were irradiated with about 70, 000r of gamma-rays before the inoculation in the medium, amounts of phosphate in the fractions of DNA, RNA, nucleotides and protein decreased during the culture, compared with those of the control. However, the phosphate content in the fraction of acid-insoluble polyphosphate of the irradiated cells increased than those of the control. In the growing period of the algae in a Mo-free, medium, amounts of acid-soluble total phosphate and nucleotides of the cells increased, while the amounts of residual protein and RNA decresed compared with those of the normal cells. Amounts of alkali-labile protein and phospholipid of the cells grown in a B-free medium decreased, whereas amount of phosphate in acid-soluble fraction increased compared with the control. In general, the contents of protein and RNA in each microelement deficient cells decreased more or less, compared with those in the normal cells.in the normal cells.
This study was executed to measure the biosynthesis of arachidonic acid metabolic products in chronic periapical lesions, to compare the products among periapical granuloma, periapical cyst and chronic periapical abscess, and to understand the pathogensis of chronic periapical lesions. Tissues from 33 chronic periapical lesions of human teeth were enucleated during endodontic surgery. large part of each tissue was contained in liquid nitrogen immediately and the other was examined histologically. In histologically diagnosed 8 cases of periapical granuloma, 9 cases of periapical cyst and 8 cases of chronic periapical abscess. the tissues were homogenatecl and incubated with $_{14}C$-arachidonic acid. Lipid solvent extracts were separated by thin layer chromatography to be analyzed by autoradiography and TLC analyzer. 1. $TXB_2$, 6-keto-$PGF_1{\alpha}$ and $PGE_2$, $LTB_4$, HETEs, and unidentified product which are metabolic products of arachidonic acid were measured in the tissues of chronic peripaical lesions. 2. In all of periapical granuloma, cyst and abscess, the conversion rate of HETEs among all products was the highest(P<0.05), and the percentage of HETEs in total converted products was also the highest(P<0.05). 3. The concentration of each arachidonic acid product was higher in chronic periapical absecss than in periapical granuloma and cyst(P<0.05). The concentration of $TXB_2$ and HETEs in periapical cyst were hight than in periapical granuloma. 4. The relative amounts of total products from lipoxygenase pathway to those from cyclo-oxygenase pathway were about 7 fold in chronic periapical lesions. There was no difference among periapical granuloma, cyst and abscess(P<0.05). The total amount of products from each pathway were higher in chronic periapical abscess than in periapical cyst and granuloma.
This study was conducted to examine the effects of dietary xylooligosaccharides on hepatic HMG-CoA reductase activity and morphological exchange of liver in rats fed high fat diet. Sprague-Dawley male rats weighing 100 $\pm$ 10 g were randomly divided into four groups, two normal diets and two high fat diets containing 1% cholesterol and 10% lard. Two normal diets were classified into a basal diet (normal group) and 10% xylooligosaccharide diet (NX group). The high fat diet groups were classified into a HF group without xylooligosaccharides diet and HFX group supplemented 10% xylooligosacchride diet. Experimental diets were fed ad libidum to the rats for 4 weeks and then they were sacrificed. The body weight of high fat diet (HF group) was increased more than that of normal group, but it was significantly decreased by xylooligosacchrides supplementation. The food intake was not significantly different among the all groups. The weight of liver, small intestine and cecum of all xylooligosaccharide supplemented groups were significantly heavier than those of normal and HF groups. The activity of hepatic HMG-CoA reductase, a rate limiting enzyme of cholesterol biosynthesis, in xylooligosaccharide supplemented groups was higher than that of HF group. Light micrographs revealed that the structures of hepatocytes in xylooligosaccharide supplemented groups were preserved well, compared to HF group. The xylooligosaccharide supplementation exerted a lipid-lowering action by decreasing cholesterol and triglycerides contents in hepatic tissue. In conclusion, the activity of hepatic HMG-CoA reductase and damage of liver in rats fed high fat diets were improved by dietary xylooligosaccharides.
Nan, Jinyan;Lee, Ji Seon;Lee, Seung-Ah;Lee, Dong-Sup;Park, Kyong Soo;Chung, Sung Soo
Molecules and Cells
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제44권9호
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pp.637-646
/
2021
Free fatty acids are converted to acyl-CoA by long-chain acyl-CoA synthetases (ACSLs) before entering into metabolic pathways for lipid biosynthesis or degradation. ACSL family members have highly conserved amino acid sequences except for their N-terminal regions. Several reports have shown that ACSL1, among the ACSLs, is located in mitochondria and mainly leads fatty acids to the β-oxidation pathway in various cell types. In this study, we investigated how ACSL1 was localized in mitochondria and whether ACSL1 overexpression affected fatty acid oxidation (FAO) rates in C2C12 myotubes. We generated an ACSL1 mutant in which the N-terminal 100 amino acids were deleted and compared its localization and function with those of the ACSL1 wild type. We found that ACSL1 adjoined the outer membrane of mitochondria through interaction of its N-terminal region with carnitine palmitoyltransferase-1b (CPT1b) in C2C12 myotubes. In addition, overexpressed ACSL1, but not the ACSL1 mutant, increased FAO, and ameliorated palmitate-induced insulin resistance in C2C12 myotubes. These results suggested that targeting of ACSL1 to mitochondria is essential in increasing FAO in myotubes, which can reduce insulin resistance in obesity and related metabolic disorders.
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