• Molecules and Cells
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• 제37권1호
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• pp.51-57
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• 2014

NOG1 is a nucleolar GTPase that is critical for 60S ribosome biogenesis. Recently, NOG1 was identified as one of the downstream regulators of target of rapamycin (TOR) in yeast. It is reported that TOR is involved in regulating lifespan and fat storage in Caenorhabditis elegans. Here, we show that the nog1 ortholog (T07A9.9: nog-1) in C. elegans regulates growth, development, lifespan, and fat metabolism. A green fluorescence protein (GFP) promoter assay revealed ubiquitous expression of C. elegans nog-1 from the early embryonic to the adult stage. Furthermore, the GFP-tagged NOG-1 protein is localized to the nucleus, whereas the aberrant NOG-1 protein is concentrated in the nucleolus. Functional studies of NOG-1 in C. elegans further revealed that nog-1 knockdown resulted in smaller broodsize, slower growth, increased life span, and more fat storage. Moreover, nog-1 over-expression resulted in decreased life span. Taken together, our data suggest that nog-1 in C. elegans may be an important player in regulating life span and fat storage via the insulin/IGF pathway.

• 한방재활의학과학회지
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• 제29권4호
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• pp.15-27
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• 2019

Objectives This study was performed to evaluate anti-obesity effects of Crataegus pinnatifida (CP) on high-fat-diet induced obese mice. Methods The experimental animals were divided into four groups: normal diet (NOR) group, high fat diet (HFD) group, HFD+Xenical (XEN) group, and HFD+CP (CP) group. NOR group was fed a normal diet and the other three groups were fed high fat diet during the experiment. After the first two weeks of diet, XEN group and CP group were administered with XEN or CP for seven weeks, respectively. After that, we measured body weight, liver weight, fat weight, food intake, and serum concentrations of lipids and liver enzymes. Also the liver, intestine, fat tissue was removed to estimate the obesity-related mRNA expressions and the stool sample was collected to analyze the gut microbiota. Results We found that body weight, fat weight, and triglyceride level were decreased significantly in CP group compared to HFD group. Also CP significantly suppressed gene expressions associated with lipogenesis and inflammation, and increased gene expressions of browning of white adipose tissue and mitochondrial biogenesis. Moreover, it shifted the microbial diversity closer to that of NOR group and increased Firmicutes/Bacteriodetes ratio. Conclusions These results suggest that CP decrease body weight, fat weight and serum triglyceride. Also it inhibit inflammation and adipogenesis, altering gut microbial diversity and abundance. In conclusion, CP could be used as a therapeutic drug for obesity via gut microbiota modulation.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 추계학술대회
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• pp.90-90
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• 2019

Hibiscus syriacus exhibited promising potential as a new source of food and colorants containing various anthocyanins. However, the function of anthocyanins from H. syriacus has not been investigated. In the current study, we evaluated whether anthocyanins from the H. syriacus varieties Pulsae and Paektanshim (PS and PTS) inhibit melanin biogenesis. B16F10 cells and zebrafish larvae were exposed to PS and PTS in the presence or absence of ${\alpha}$-melanocyte-stimulating hormone (${\alpha}$-MSH), and melanin contents accompanied by its regulating genes and proteins were analyzed. PS and PTS moderately downregulated mushroom tyrosinase activity in vitro, but significantly decreased extracellular and intracellular melanin production in B16F10 cells, and inhibited ${\alpha}$-MSH-induced expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. PS and PTS also attenuated pigmentation in ${\alpha}$-MSH-stimulated zebrafish larvae. Furthermore, PS and PTS activated the phosphorylation of extracellular signal-regulated kinase (ERK), whereas PD98059, a specific ERK inhibitor, completely reversed PS- and PTS-mediated anti-melanogenic activity in B16F10 cells and zebrafish larvae, which indicates that PS- and PTS-mediated anti-melanogenic activity is due to ERK activation. Moreover, chromatography data showed that PS and PTS possessed 17 identical anthocyanins as a negative regulator of ERK. These findings suggested that anthocyanins from PS and PTS inhibited melanogenesis in vitro and in vivo by activating the ERK signaling pathway.

• Journal of Veterinary Science
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• 제22권1호
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• pp.4.1-4.13
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• 2021

Background: Microsporum canis is a zoonotic disease that can cause dermatophytosis in animals and humans. Objectives: In clinical practice, ketoconazole (KTZ) and other imidazole drugs are commonly used to treat M. canis infection, but its molecular mechanism is not completely understood. The antifungal mechanism of KTZ needs to be studied in detail. Methods: In this study, one strain of fungi was isolated from a canine suffering with clinical dermatosis and confirmed as M. canis by morphological observation and sequencing analysis. The clinically isolated M. canis was treated with KTZ and transcriptome sequencing was performed to identify differentially expressed genes in M. canis exposed to KTZ compared with those unexposed thereto. Results: At half-inhibitory concentration (½MIC), compared with the control group, 453 genes were significantly up-regulated and 326 genes were significantly down-regulated (p < 0.05). Quantitative reverse transcription polymerase chain reaction analysis verified the transcriptome results of RNA sequencing. Gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the 3 pathways of RNA polymerase, steroid biosynthesis, and ribosome biogenesis in eukaryotes are closely related to the antifungal mechanism of KTZ. Conclusions: The results indicated that KTZ may change cell membrane permeability, destroy the cell wall, and inhibit mitosis and transcriptional regulation through CYP51, SQL, ERG6, ATM, ABCB1, SC, KER33, RPA1, and RNP genes in the 3 pathways. This study provides a new theoretical basis for the effective control of M. canis infection and the effect of KTZ on fungi.

• Nutrition Research and Practice
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• 제13권1호
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• pp.3-10
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• 2019

BACKGROUND/OBJECTIVES: The $NAD^+$ precursor nicotinamide riboside (NR) is a type of vitamin $B_3$ found in cow's milk and yeast-containing food products such as beer. Recent studies suggested that NR prevents hearing loss, high-fat diet-induced obesity, Alzheimer's disease, and mitochondrial myopathy. The objective of this study was to investigate the effects of NR on inflammation and mitochondrial biogenesis in AML12 mouse hepatocytes. MATERIALS/METHODS: A subset of hepatocytes was treated with palmitic acid (PA; $250{\mu}M$) for 48 h to induce hepatocyte steatosis. The hepatocytes were treated with NR ($10{\mu}M$ and 10 mM) for 24 h with and without PA. The cell viability and the levels of sirtuins, inflammatory markers, and mitochondrial markers were analyzed. RESULTS: Cytotoxicity of NR was examined by PrestoBlue assay. Exposure to NR had no effect on cell viability or morphology. Gene expression of sirtuin 1 (Sirt1) and Sirt3 was significantly upregulated by NR in PA-treated hepatocytes. However, Sirt1 activities were increased in hepatocytes treated with low-dose NR. Hepatic pro-inflammatory markers including tumor necrosis factor-alpha and interleukin-6 were decreased in NR-treated cells. NR upregulated anti-inflammatory molecule adiponectin, and, tended to down-regulate hepatokine fetuin-A in PA-treated hepatocytes, suggesting its inverse regulation on these cytokines. NR increased levels of mitochondrial markers including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$, carnitine palmitoyltransferase 1, uncoupling protein 2, transcription factor A, mitochondrial and mitochondrial DNA in PA-treated hepatocytes. CONCLUSIONS: These data demonstrated that NR attenuated hepatic inflammation and increased levels of mitochondrial markers in hepatocytes.

• The Plant Pathology Journal
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• 제35권3호
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• pp.257-273
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• 2019

Tomato (Solanum lycopersicum) is one of the most widely grown and economically important vegetable crops in the world. Tomato chlorosis virus (ToCV) is one of the recently emerged viruses of tomato distributed worldwide. ToCV-tomato interaction was investigated at the molecular level for determining changes in the expression of tomato genes in response to ToCV infection in this study. A cDNA library enriched with genes induced in response to ToCV infection were constructed and 240 cDNAs were sequenced from this library. The macroarray analysis of 108 cDNAs revealed that the expression of 92 non-redundant tomato genes was induced by 1.5-fold or greater in response to ToCV infection. The majority of ToCV-induced genes identified in this study were associated with a variety of cellular functions including transcription, defense and defense signaling, metabolism, energy, transport facilitation, protein synthesis and fate and cellular biogenesis. Twenty ToCV-induced genes from different functional groups were selected and induction of 19 of these genes in response to ToCV infection was validated by RT-qPCR assay. Finally, the expression of 6 selected genes was analyzed in different stages of ToCV infection from 0 to 45 dpi. While the expression of three of these genes was only induced by ToCV infection, others were induced both by ToCV infection and wounding. The result showed that ToCV induced the basic defense response and activated the defense signaling in tomato plants at different stages of the infection. Functions of these defense related genes and their potential roles in disease development and resistance to ToCV are also discussed.

• Journal of Microbiology and Biotechnology
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• 제31권5호
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• pp.645-658
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• 2021

Porins are essential for the viability of Gram-negative bacteria. They ensure the uptake of nutrients, can be involved in the maintenance of outer membrane integrity and define the antibiotic or drug resistance of organisms. The function and structure of porins in proteobacteria is well described, while their function in photoautotrophic cyanobacteria has not been systematically explored. We compared the domain architecture of nine putative porins in the filamentous cyanobacterium Anabaena sp. PCC 7120 and analyzed the seven candidates with predicted OprB-domain. Single recombinant mutants of the seven genes were created and their growth capacity under different conditions was analyzed. Most of the putative porins seem to be involved in the transport of salt and copper, as respective mutants were resistant to elevated concentrations of these substances. In turn, only the mutant of alr2231 was less sensitive to elevated zinc concentrations, while mutants of alr0834, alr4741 and all4499 were resistant to high manganese concentrations. Notably the mutant of alr4550 shows a high sensitivity against harmful compounds, which is indicative for a function related to the maintenance of outer membrane integrity. Moreover, the mutant of all5191 exhibited a phenotype which suggests either a higher nitrate demand or an inefficient nitrogen fixation. The dependency of porin membrane insertion on Omp85 proteins was tested exemplarily for Alr4550, and an enhanced aggregation of Alr4550 was observed in two omp85 mutants. The comparative analysis of porin mutants suggests that the proteins in parts perform distinct functions related to envelope integrity and solute uptake.

• Journal of Ginseng Research
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• 제46권3호
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• pp.454-463
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• 2022

Background: Gintonin-enriched fraction (GEF), a non-saponin fraction of ginseng, is a novel glycolipoprotein rich in hydrophobic amino acids. GEF has recently been shown to regulate lipid metabolism and browning in adipocytes; however, the mechanisms underlying its effects on energy metabolism and whether it affects sarcopenic obesity are unclear. We aimed to evaluate the effects of GEF on skeletal muscle atrophy in high-fat diet (HFD)-induced obese mice. Methods: To examine the effect of GEF on sarcopenic obesity, 4-week-old male ICR mice were used. The mice were divided into four groups: chow diet (CD), HFD, HFD supplemented with 50 mg/kg/day GEF, or 150 mg/kg/day GEF for 6 weeks. We analyzed body mass gain and grip strength, histological staining, western blot analysis, and immunofluorescence to quantify changes in sarcopenic obesity-related factors. Results: GEF inhibited body mass gain while HFD-fed mice gained 22.7 ± 2.0 g, whereas GEF-treated mice gained 14.3 ± 1.2 g for GEF50 and 11.8 ± 1.6 g for GEF150 by downregulating adipogenesis and inducing lipolysis and browning in white adipose tissue (WAT). GEF also enhanced mitochondrial biogenesis threefold in skeletal muscle. Furthermore, GEF-treated skeletal muscle exhibited decreased expression of muscle-specific atrophic genes, and promoted myogenic differentiation and increased muscle mass and strength in a dose-dependent manner (p < 0.05). Conclusion: These findings indicate that GEF may have potential uses in preventing sarcopenic obesity by promoting energy expenditure and attenuating skeletal muscle atrophy.

• BMB Reports
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• 제55권7호
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• pp.354-359
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• 2022

MitoNEET, a mitochondrial outer membrane protein containing the Asn-Glu-Glu-Thr (NEET) sequence, controls the formation of intermitochondrial junctions and confers autophagy resistance. Moreover, mitoNEET as a mitochondrial substrate undergoes ubiquitination by activated Parkin during the initiation of mitophagy. Therefore, mitoNEET is linked to the regulation of autophagy and mitophagy. Mitophagy is the selective removal of the damaged or unnecessary mitochondria, which is crucial to sustaining mitochondrial quality control. In numerous human diseases, the accumulation of damaged mitochondria by impaired mitophagy has been observed. However, the therapeutic strategy targeting of mitoNEET as a mitophagy-enhancing mediator requires further research. Herein, we confirmed that mitophagy is indeed activated by mitoNEET inhibition. CCCP (carbonyl cyanide m-chlorophenyl hydrazone), which leads to mitochondrial depolarization, induces mitochondrial dysfunction and superoxide production. This, in turn, contributes to the induction of mitophagy; mitoNEET protein levels were initially increased before an increase in LC3-II protein following CCCP treatment. Pharmacological inhibition of mitoNEET using mitoNEET Ligand-1 (NL-1) promoted accumulation of Pink1 and Parkin, which are mitophagy-associated proteins, and activation of mitochondria-lysosome crosstalk, in comparison to CCCP alone. Inhibition of mitoNEET using NL-1, or mitoNEET shRNA transfected into RAW264.7 cells, abrogated CCCP-induced ROS and mitochondrial cell death; additionally, it activated the expression of PGC-1α and SOD2, regulators of oxidative metabolism. In particular, the increase in PGC-1α, which is a major regulator of mitochondrial biogenesis, promotes mitochondrial quality control. These results indicated that mitoNEET is a potential therapeutic target in numerous human diseases to enhance mitophagy and protect cells by maintaining a network of healthy mitochondria.

• Journal of Animal Science and Technology
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• 제64권4호
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• pp.752-769
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• 2022

Wheat gluten is an increasingly common ingredient in poultry diets but its impact on the small intestine in chicken is not fully understood. This study aimed to identify effects of high-gluten diets on chicken small intestines and the variation of their associated transcriptional responses by age. A total of 120 broilers (Ross Strain) were used to perform two animal experiments consisting of two gluten inclusion levels (0% or 25%) by bird's age (1 week or 4 weeks). Transcriptomics and histochemical techniques were employed to study the effect of gluten on their duodenal mucosa using randomly selected 12 broilers (3 chicks per group). A reduction in feed intake and body weight gain was found in the broilers fed a high-gluten containing diet at both ages. Histochemical photomicrographs showed a reduced villus height to crypt depth ratio in the duodenum of gluten-fed broilers at 1 week. We found mainly a significant effect on the gene expression of duodenal mucosa in gluten-fed broilers at 1 week (289 differentially expressed genes [DEGs]). Pathway analyses revealed that the significant DEGs were mainly involved in ribosome, oxidative phosphorylation, and peroxisome proliferator-activated receptor (PPAR) signaling pathways. These pathways are involved in ribosome protein biogenesis, oxidative phosphorylation and fatty acid metabolism, respectively. Our results suggest a pattern of differential gene expression in these pathways that can be linked to chronic inflammation, suppression of cell proliferation, cell cycle arrest and apoptosis. And via such a mode of action, high-gluten inclusion levels in poultry diets could lead to the observed retardation of villi development in the duodenal mucosa of young broiler chicken.