• International Journal of Oral Biology
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• 제41권1호
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• pp.45-51
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• 2016

Rutin (3,3',4',5,7-pentahydroxyflavone-3-rhamnoglucoside) is a bioactive flavonoid from the plant kingdom. Rutin has been studied as potential anticancer agent due to its wide range of pharmacological properties including antioxidative, anti-inflammatory and anticancer. Autophagy is a conserved intracellular catabolic pathway to maintain cell homeostasis by formation of autophagosome. Processing of autophagy involves various molecules including ULK1 protein kinase complex, Beclin-1-Vps34 lipid kinase complex, ATG5, ATG12, and LC3 (light chain 3). Cargo-carried autophagosomes fuse with lysosomes resulting in autophagolysosome to eliminate vesicles and degrade cargo. However, the actions of rutin on autophagy are not clearly understood. In this study, we analyzed the effect of rutin on autophagy and inflammation in cancer cell lines. Interestingly, rutin induced autophagy in leukemia (THP-1), oral (CA9-22), and lung (A549) cell lines. TNF-${\alpha}$, key modulator of inflammation, was upregulated by inhibition of rutin-induced autophagy. Taken together, these data indicated that rutin induced autophagy and consequently suppressed TNF-${\alpha}$ production.

• 대한수의학회지
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• 제47권4호
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• pp.371-378
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• 2007

To understand the role of $PM_{2X}/P_{2Y}$ receptor in cortex region of kidney and renal artery, molecular and functional analysis of $PM_{2X}/P_{2Y}$ receptor by pharmacophysiological skill in conventional swine tissues were performed. In functional analysis of $P_{2Y}$ receptor for vascular relaxation, 2-methylthio adenosine triphosphate, a strong agonist of $P_{2Y}$ receptor, induced relaxation of noradrenaline (NA)-precontracted renal artery in a dose-dependent manner. Strikingly, relaxative effect of ATP, 2-msATP, agonists of $P_{2Y}$ receptor, abolished by treatment of reactive blue 2, a putative $P_{2Y}$ receptor antagonist. In contrast, no significant differences of gene encoding $PM_{2X}/P_{2Y}$ and protein expression in immortalized suprachiasmatic nucleus from brain, primary isolated vascular smooth muscle cells from renal artery of pigs and HEK293 from human embryonic kidney under with/without adenosine triphosphate were observed. Taken together, the relationship between molecular and functional characteristic of $PM_{2X}/P_{2Y}$ receptors in conventional pig should be considered that they are another important factor which regulate the kidney function in swine. Based on this study, we propose the purinergic receptor as well as adrenergic and cholinergic receptors is an essential component of the renal homeostasis.

• Molecules and Cells
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• 제40권10호
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• pp.752-760
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• 2017

A2B adenosine receptor (A2BAR) is known to be the regulator of bone homeostasis, but its regulatory mechanisms in osteoclast formation are less well-defined. Here, we demonstrate the effect of A2BAR stimulation on osteoclast differentiation and activity by RANKL. A2BAR was expressed in bone marrow-derived monocyte/macrophage (BMM) and RANKL increased A2BAR expression during osteoclastogenesis. A2BAR stimulation with its specific agonist BAY 60-6583 was sufficient to inhibit the activation of ERK1/2, p38 MAP kinases and $NF-{\kappa}B$ by RANKL as well as it abrogated cell-cell fusion in the late stage of osteoclast differentiation. Stimulation of A2BAR suppressed the expression of osteoclast marker genes, such as c-Fos, TRAP, Cathepsin-K and NFATc1, induced by RANKL, and transcriptional activity of NFATc1 was also inhibited by stimulation of A2BAR. A2BAR stimulation caused a notable reduction in the expression of Atp6v0d2 and DC-STAMP related to cell-cell fusion of osteoclasts. Especially, a decrease in bone resorption activity through suppression of actin ring formation by A2BAR stimulation was observed. Taken together, these results suggest that A2BAR stimulation inhibits the activation of ERK1/2, p38 and $NF-{\kappa}B$ by RANKL, which suppresses the induction of osteoclast marker genes, thus contributing to the decrease in osteoclast cell-cell fusion and bone resorption activity.

• Korean Journal of Acupuncture
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• 제36권4호
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• pp.200-209
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• 2019

Objectives : The liver is rich in mitochondria and it plays a key role in whole-body energy homeostasis. Mitochondria is double membrane-bound organelle that supplies energy for intracellular metabolism including Krebs cycle and beta-oxidation. Acupuncture is known to stimulate and regulate the flow of energy. To explore the effect of acupuncture on the mitochondrial respiratory chain activity in the rats' livers, the activity of mitochondrial respiratory chain complexes I to IV was observed. Methods : The rats were divided into 4 groups; Normal 1 (no acupuncture treatment and anesthesia for 5 min), Normal 2 (no acupuncture treatment and anesthesia for 10 min), MA1 (acupuncture treatment at bilateral LR3 under anesthesia for 5 min), and MA2 (acupuncture treatment at bilateral LR3 under anesthesia for 10 min). All rats were sacrificed and the livers were examined for respiratory chain change. Results : There was no difference in ubiquinon oxidoreductase, succinate dehydrogenase, and ubiquinol cytochrome C oxidoreductase after acupuncture at LR3. Acupuncture at LR3 for 10 min increased the activity of cytochrome C oxidase compared with no acupuncture groups. Conclusions : Acupuncture at LR3 mediated mitochondrial respiratory chain activity via the cytochrome C oxidase signaling pathway in the livers of rats.

• KSBB Journal
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• 제29권1호
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• pp.50-57
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• 2014

NF-${\kappa}B$ is a transcriptional factor which is involved in many biological processes including immunity, inflammation, and cell survival. Many investigators studied on the mechanism involved in activation of NF-${\kappa}B$ signalling pathway via ubiquitination and degradation of $I{\kappa}B$ regarding skin disease. Some specific molecules including Akt, MEK, p38 MAP Kinase, Stat3, et al. represent convergence points and key regulatory proteins in signaling pathways controlling cellular events such as growth and differentiation, energy homeostasis, and the response to stress and inflammation. Ultraviolet (UV) irradiation has many adverse effects on skin, including inflammation, alteration in the extracellular matrix, cellular senescence, apoptosis and skin cancer. Prunus mume, a naturally derived plant extract, has beneficial biological activities as blood fluidity improvement, anti-fatigue action, antioxidative and free radical scavenging activities, inhibiting the motility of Helicobacter pyolri. Previous reports on various beneficial function prompted us to investigate UVB-induced or other immunostimulated biological marker regarding P. mume extract. P. mume extract suppresses UVB-induced cyclooxygenase-2 (COX-2) expression in mouse skin epidermal JB6 P+ cells. The activation of activator protein-1 and nuclear factor-${\kappa}B$ induced by UVB was dose-dependently inhibited by P. mume extract treatment. This results suggest that P. mume extracts might be used as a potential agents for protection of inflammation or UVB induced skin damage.

• Molecules and Cells
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• 제37권11호
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• pp.827-832
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• 2014

The balance between bone formation by osteoblasts and destruction of mineralized bone matrix by osteoclasts is important for bone homeostasis. The increase of osteoclast differentiation by RANKL induces bone diseases such as osteoporosis. Recent studies have shown that insulin is one of main factors mediating the cross-talk between bone remodeling and energy metabolism. However, the systemic examination of insulin-induced differential gene expression profiles in osteoclasts has not been extensively studied. Here, we investigated the global effects of insulin on osteoclast precursors at the level of gene transcription by microarray analysis. The number of genes that were up-regulated by ${\geq}1.5$ fold after insulin treatment for 6 h, 12 h, or 24 h was 76, 73, and 39; and 96, 83, and 54 genes were down-regulated, respectively. The genes were classified by 20 biological processes or 24 molecular functions and the number of genes involved in 'development processes' and 'cell proliferation and differentiation' was 25 and 18, respectively, including Inhba, Socs, Plk3, Tnfsf4, and Plk1. The microarray results of these genes were verified by real-time RT-PCR analysis. We also compared the effects of insulin and RANKL on the expression of these genes. Most genes had a very similar pattern of expressions in insulin- and RANKL-treated cells. Interestingly, Tnfsf4 and Inhba genes were affected by insulin but not by RANKL. Taken together, these results suggest a potential role for insulin in osteoclast biology, thus contributing to the understanding of the pathogenesis and development of therapeutics for numerous bone and metabolic diseases.

• 한국환경농학회지
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• 제30권4호
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• pp.395-401
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• 2011

BACKGROUND: Potassium (K) is one of the macronutrients which are essential for plant growth and development. Its deficiency in paddy soils is becoming one of the limiting factors for increasing rice yield in Asia. METHODS AND RESULTS: To investigate physiological symptoms under K-starvation (NP) compared with complete media (NPK) condition, we measured shoot/root length, weight, nutrients, and patterns of protein expression. The shoot growth was significantly reduced, but root growth was not affected by K-starvation. However, biomasses were decreased in both shoot and root. Uptake of K was reduced up to 85%, while total concentrations of P, Ca, Mg, Na were increased in root and shoot. To better understand the starved K mechanism of rice, comparative proteome analysis for proteins isolated from rice leaves was conducted using 2-DGE. Five spots of differentially expressed proteins were analyzed by MALDI-TOF MS. Analysis of these K-starvation response proteins suggested that they were involved in metabolism and defense. CONCLUSION(s): Physiological and 2-DGE based proteomics approach used in our study results in observation of morphology or nutrients change and identification of K-starvation responsive proteins in rice root. These results have important roles in maintaining nutrient homeostasis and would also be useful for further characterization of protein function in plant K nutrition.

• 동의생리병리학회지
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• 제33권4호
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• pp.191-197
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• 2019

This study aims to evaluate the effects of the root bark of Morus alba (RMA) on the regulation of the Hippo-YAP pathway. Hippo-YAP signaling is a critical regulator in controlling organ size and tissue homeostasis. Hippo, the serine/threonine kinase phosphorylate the LATS. Phosphorylated LATS then phosphorylates and inactivates the YAP and TAZ, which are two closely related transcriptional co-activator. Here we report RMA activates the Hippo signaling, thereby inhibits the YAP/TAZ activity. First, we examine the cytotoxic effects of RMA by MTT assay. RMA was cytotoxic at concentrations higher than $50{\mu}g/ml$ in HEK293A cells. The reporter gene assay was performed to measure the activity of TEAD, a key transcription factor that controls cell growth and proliferation. RMA significantly suppressed the luciferase activity. By phos-taq gel shift assay, and western blotting, we showed that RMA enhanced the phosphorylation of YAP in wild type cells, but not in LATS1/2 knock out cells, which means RMA activates classical Hippo pathway. RMA induced the cytoplasmic sequestration of YAP. RMA also suppressed the mRNA expression of CTGF and CYR61; the two major YAP dependent genes. Taken together, RMA is considered to be a good candidate for proliferative disease such as cancer, by facilitating cell death through activating the Hippo signaling pathway.

• 생약학회지
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• 제53권1호
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• pp.42-48
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• 2022

In order to maintain bone homeostasis, it is necessary to balance bone resorption and remodeling through the differentiation of osteoclasts that absorb old bone and osteoblasts that form new bone. However, bone resorption due to excessive osteoclast differentiation is a major cause of osteoporosis and controlling excessive osteoclast differentiation has been known as a treatment strategy for osteoporosis. Therefore, in this study, the effect of an ethanol extract of Sphaerotylus antarcticus Kirkpatrick, 1907 (SAE), polar-derived sponge with unknown biological activity, on the osteoclast differentiation process of RANKL-induced RAW264.7 cells and the generated ROS was evaluated. In the study results, SAE down-regulated the formation and function of RANKL-induced osteoclasts and osteoclast differentiation specific proteins, genes in a concentration-dependent manner. In addition, it was possible to confirm the result of restoring the lost antioxidant enzyme along with down-regulation of ROS generated by RANKL. Therefore, in this study, we propose the possibility of SAE as a potential regulator of osteoporosis due to excessive osteoclast differentiation and report the biological value of the diversity of marine-derived natural products by identifying the first biological activity against SAE that is not yet known.

• The Korean Journal of Physiology and Pharmacology
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• 제27권4호
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• pp.311-323
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• 2023

Ion homeostasis, which is regulated by ion channels, is crucial for intracellular signaling. These channels are involved in diverse signaling pathways, including cell proliferation, migration, and intracellular calcium dynamics. Consequently, ion channel dysfunction can lead to various diseases. In addition, these channels are present in the plasma membrane and intracellular organelles. However, our understanding of the function of intracellular organellar ion channels is limited. Recent advancements in electrophysiological techniques have enabled us to record ion channels within intracellular organelles and thus learn more about their functions. Autophagy is a vital process of intracellular protein degradation that facilitates the breakdown of aged, unnecessary, and harmful proteins into their amino acid residues. Lysosomes, which were previously considered protein-degrading garbage boxes, are now recognized as crucial intracellular sensors that play significant roles in normal signaling and disease pathogenesis. Lysosomes participate in various processes, including digestion, recycling, exocytosis, calcium signaling, nutrient sensing, and wound repair, highlighting the importance of ion channels in these signaling pathways. This review focuses on different lysosomal ion channels, including those associated with diseases, and provides insights into their cellular functions. By summarizing the existing knowledge and literature, this review emphasizes the need for further research in this field. Ultimately, this study aims to provide novel perspectives on the regulation of lysosomal ion channels and the significance of ion-associated signaling in intracellular functions to develop innovative therapeutic targets for rare and lysosomal storage diseases.