• Nutrition Research and Practice
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• 제13권3호
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• pp.196-204
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• 2019

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disease triggered by epigenetic alterations, including lysine acetylation at histone or non-histone proteins, affecting the stability or transcription of lipogenic genes. Although various natural dietary compounds have anti-lipogenic effects, their effects on the acetylation status and lipid metabolism in the liver have not been thoroughly investigated. MATERIALS/METHODS: Following oleic-palmitic acid (OPA)-induced lipid accumulation in HepG2 cells, the acetylation status of histone and non-histone proteins, HAT activity, and mRNA expression of representative lipogenic genes, including $PPAR{\gamma}$, SREBP-1c, ACLY, and FASN, were evaluated. Furthermore, correlations between lipid accumulation and HAT activity for 22 representative natural food extracts (NExs) were evaluated. RESULTS: Non-histone protein acetylation increased following OPA treatment and the acetylation of histones H3K9, H4K8, and H4K16 was accelerated, accompanied by an increase in HAT activity. OPA-induced increases in the mRNA expression of lipogenic genes were down-regulated by C-646, a p300/CBP-specific inhibitor. Finally, we detected a positive correlation between HAT activity and lipid accumulation (Pearson's correlation coefficient = 0.604) using 22 NExs. CONCLUSIONS: Our results suggest that NExs have novel applications as nutraceutical agents with HAT inhibitor activity for the prevention and treatment of NAFLD.

• The Korean Journal of Physiology and Pharmacology
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• 제22권4호
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• pp.457-465
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• 2018

The expression of BCL-2 interacting cell death suppressor (BIS), an anti-stress or anti-apoptotic protein, has been shown to be regulated at the transcriptional level by heat shock factor 1 (HSF1) upon various stresses. Recently, HSF1 was also shown to bind to BIS, but the significance of these protein-protein interactions on HSF1 activity has not been fully defined. In the present study, we observed that complete depletion of BIS using a CRISPR/Cas9 system in A549 non-small cell lung cancer did not affect the induction of heat shock protein (HSP) 70 and HSP27 mRNAs under various stress conditions such as heat shock, proteotoxic stress, and oxidative stress. The lack of a functional association of BIS with HSF1 activity was also demonstrated by transient downregulation of BIS by siRNA in A549 and U87 glioblastoma cells. Endogenous BIS mRNA levels were significantly suppressed in BIS knockout (KO) A549 cells compared to BIS wild type (WT) A549 cells at the constitutive and inducible levels. The promoter activities of BIS and HSP70 as well as the degradation rate of BIS mRNA were not influenced by depletion of BIS. In addition, the expression levels of the mutant BIS construct, in which 14 bp were deleted as in BIS-KO A549 cells, were not different from those of the WT BIS construct, indicating that mRNA stability was not the mechanism for autoregulation of BIS. Our results suggested that BIS was not required for HSF1 activity, but was required for its own expression, which involved an HSF1-independent pathway.

• Archives of Pharmacal Research
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• 제27권2호
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• pp.127-135
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• 2004

Multiple drug administration is common in elderly, HIV, and cancer patients. Such treatments may result in drug-drug interactions due to interference at the metabolic enzyme level, and due to modulation of transporter protein functions. Both kinds of interference may result in altered drug distribution and toxicity in the human body. In this review, we have dealt with drug-drug interactions related to the most studied human transporter, P-glycoprotein. This transporter is constitutively expressed in several sites in the human body. Its function can be studied in vitro with different cell lines expressing P-glycoprotein in experiments using methods and equipment such as flow cytometry, cell proliferation, cell-free ATP as activity determination and Transwell culture equipment. In vivo experiments can be carried out by mdr1a(-/-) animals and by noninvasive methods such as NMR spectrometry. Some examples are also given for determination of possible drug-drug interactions using the above-mentioned cell lines and methods. Such preclinical studies may influence decisions concerning the fate of new drug candidates and their possible dosages. Some examples of toxicities obtained in clinics and summarized in this review indicate careful consideration in cases of polypharmacy and the requirement of preclinical studies in drug development activities.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.561-568
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• 2014

Background: The skin is the largest body organ that regulates excretion of metabolic waste products, temperature, and plays an important role in body protection against environmental physical and chemical, as well as biological factors. These include agents that may act as oxidants or catalysts of reactions producing reactive oxygen species (ROS), reactive nitrogen species (RNS), and other oxidants in skin cells. An increased amount of the oxidants, exceeding the antioxidant defense system capacity is called oxidative stress, leading to chronic inflammation, which, in turn, can cause collagen fragmentation and disorganization of collagen fibers and skin cell functions, and thus contribute to skin diseases including cancer. Moreover, research suggests that oxidative stress participates in all stages of carcinogenesis. We report here a summary of the present state of knowledge on the role of oxidative stress in pathogenesis of dermatologic diseases, defensive systems against ROS/RNS, and discuss how physical activity may modulate skin diseases through effects on oxidative stress. The data show duality of physical activity actions: regular moderate activity protects against ROS/RNS damage, and endurance exercise with a lack of training mediates oxidative stress. These findings indicate that the redox balance should be considered in the development of new antioxidant strategies linked to the prevention and therapy of skin diseases.

• 대한수의학회지
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• 제59권2호
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• pp.75-80
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• 2019

Enrofloxacin, a fluoroquinolone, is a broad-spectrum antibiotic widely used in veterinary medicine that inhibits the action of bacterial DNA gyrase, resulting in anti-bacterial effects. This study was performed to examine whether enrofloxacin has modulatory and anti-inflammatory activity on immune cells. A few studies have reported the anti-inflammatory effects of enrofloxacin. In this study, we used mouse spleen cells treated with lipopolysaccharide (LPS) and examined the effects of enrofloxacin. Several assays were performed in LPS-treated spleen cells after the enrofloxacin treatment. Enrofloxacin inhibited the metabolic activity and mitochondrial membrane potential of LPS-treated spleen cells significantly. On the other hand, enrofloxacin did not alter the proportion of the subsets in spleen cells, and did not induce cell death. The production of tumor necrosis factor-alpha in LPS-treated spleen cells was inhibited by enrofloxacin. Overall, enrofloxacin had modulatory activity in spleen cells treated with LPS. These data may broaden the use of enrofloxacin as an antibiotic with anti-inflammatory activity in veterinary clinics.

• 대한방사성의약품학회지
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• 제8권2호
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• pp.53-61
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• 2022

This study aimed to increase the targeting ability against PSMA in cell therapy using metabolic glycoengineering and biorthogonal chemistry and to visualize cell trafficking using PET imaging. Cellular membranes of THP-1 cells were decorated with azide(-N₃) using Ac₄ManNAz by metabolic glycoengineering. Engineered THP-1 cells were conjugated with DBCO-bearing fluorophore (ADIBO-Cy5.5) for 1 h at different concentrations and analyzed by confocal fluorescence microscopy and flow cytometry. For PSAM ligand conjugation to THP-1 cells, Ac₄ManNAz treated THP-1 cells were incubated with DBCO-PSMA ligand (ADIBO-GUL) at a final concentration with 100 µM for 1 h. To evaluate the effect on cell recognition, PSMA ligand conjugated THP-1 cells(as effectors) were co-cultured with PSMA positive 22RV1 (as target cells) at 3 : 1 a effector-to-target cell (E/T) ratio. The interaction between THP-1 and 22RV1 was monitored by confocal fluorescence microscopy. For preparing the radiolabeled THP-1, the cells were treated at the activity of ~ 740 kBq of [⁸⁹Zr]Zr(oxinate)₄/5 × 10⁶ cells. Radiolabeled cells were analyzed for determination of cell-associated radioactivity by gamma counting and viability using MTS assay. In the cytotoxicity assay, THP-1 cells did not have any cytotoxicity even when the Ac₄ManNAz concentration was 100 µM. In confocal microscopy and flow cytometry, THP-1 cells were efficiently labeled ADIBO-Cy5.5 in a dose-dependent manner, and the dose of 100 µM was the optimal concentration for the following experiments. The clusters of PSMA ligand-conjugated THP-1 cells and 22RV1 cells were identified, indicating cell-cell recognition over the cell surface between two types of cells. Cell radiolabeling efficiency was 54.5 ± 17.8%. THP-1 labeled with 0.09 ± 0.03 Bq/cell showed no significant cytotoxicity compared to unlabeled THP-1 up to 7 days. We successfully demonstrated that Ac₄ManNAz treated cells were efficiently conjugated with ADIBO-GUL for preparing the PSMA-targeting cells, and [⁸⁹Zr]Zr(oxinate)₄ could be used to label cells without toxicity. It suggested that PSMA-ligand conjugated cell therapy could be improved cell targeting and be monitored by PET imaging.

• Journal of Microbiology and Biotechnology
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• 제11권3호
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• pp.406-411
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• 2001

In a bacterial denitrification test with Pseudomonas sp. and anaerobic consortium, more nitrates and less substrate were consumed but less metabolic nitrite was produced under an anaerobic $H_2$ condition rather than under $N_2$ condition. In a bioelectrochemical denitrification test with the same organisms, the electrochemically reduced neutral red was confirmed to be a substitute electron donor and a reducing power like $H_2$. The biocatalytic activity of membrane-free bacterial extract, membrane fraction, and intact cell for bioelectrochemical denitrification was measured using cyclic voltammetry. When neutral red was used as an electron mediator, the electron transfer from electrode to electron acceptor (nitrate) via neutral red was not observed in the cyclic voltammogram with the membrane-free bacterial extract, but it was confirmed to gradually increase in proportion to the concentration of nitrate in that of the membrane fraction and the intact cell of Pseudomonas sp.

• Molecules and Cells
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• 제39권8호
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• pp.587-593
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• 2016

As sessile organisms, plants must be able to adapt to the environment. Plants respond to the environment by adjusting their growth and development, which is mediated by sophisticated signaling networks that integrate multiple environmental and endogenous signals. Recently, increasing evidence has shown that a bHLH transcription factor PIF4 plays a major role in the multiple signal integration for plant growth regulation. PIF4 is a positive regulator in cell elongation and its activity is regulated by various environmental signals, including light and temperature, and hormonal signals, including auxin, gibberellic acid and brassinosteroid, both transcriptionally and post-translationally. Moreover, recent studies have shown that the circadian clock and metabolic status regulate endogenous PIF4 level. The PIF4 transcription factor cooperatively regulates the target genes involved in cell elongation with hormone-regulated transcription factors. Therefore, PIF4 is a key integrator of multiple signaling pathways, which optimizes growth in the environment. This review will discuss our current understanding of the PIF4-mediated signaling networks that control plant growth.

• Asian-Australasian Journal of Animal Sciences
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• 제21권3호
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• pp.456-464
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• 2008

Avian and mammalian skeletal muscles exhibit a remarkable ability to adjust to physiological stressors induced by growth, exercise, injury and disease. The process of muscle recovery following injury and myonuclear accretion during growth is attributed to a small population of satellite cells located beneath the basal lamina of the myofiber. Several metabolic factors contribute to the activation of satellite cells in response to stress mediated by illness, injury or aging. This review will describe the regenerative properties of satellite cells, the processes of satellite cell activation and highlight the potential role of satellite cells in skeletal muscle growth, tissue engineering and meat production.

• Journal of Plant Biology
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• 제28권4호
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• pp.261-270
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• 1985

The portion of Cuscuta japonica haustorium which lies external to the host tissues, the upper haustorium, was investigated at the light- and electron-microscopic levels. The haustorium lightly contacted with the host was formed by the expansion of the epidermis and cortex of the stem at the contact side, and to have a group of meristematic cells within the haustorial cortex. When such a haustorium was closely contacted with the host, the meristematic region transformed into a primordial structure of the endophyte (endophyte primordium, EP) which may penetrate into the host tissues. EP consisted of the three kinds of cell group: dividing cells at the adaxial or proximal side; large, elongate cells (idioblasts) at the middle portion,; compressed cells at the abaxial or basal side. the idioblasts were characterized by the presence of large nucleus, dense cytoplasm, several small vacuoles, and abundant cell organelles including the multilamellar structures and cytosegresomes, and thus suggested to have a high metabolic activity. The features of the EP were discussed in relation to the possibility of the penetrating into host tissues.