• Biomolecules & Therapeutics
• /
• v.28 no.2
• /
• pp.195-201
• /
• 2020

Prostate cancer is one of the most common cancers in men. Choline PET or PET/CT has been used to visualize prostate cancer, and high levels of choline accumulation have been observed in tumors. However, the uptake system for choline and the functional expression of choline transporters in prostate cancer are not completely understood. In this study, the molecular and functional aspects of choline uptake were investigated in the LNCaP prostate cancer cell line along with the correlations between choline uptake and cell viability in drug-treated cells. Choline transporter-like protein 1 (CTL1) and CTL2 mRNA were highly expressed in LNCaP cells. CTL1 and CTL2 were located in the plasma membrane and mitochondria, respectively. [³H]Choline uptake was mediated by a single Na⁺-independent, intermediate-affinity transport system in the LNCaP cells. The anticancer drugs, flutamide and bicalutamide, inhibited cell viability and [³H]choline uptake in a concentration-dependent manner. The correlations between the effects of these drugs on cell viability and [³H]choline uptake were significant. Caspase-3/7 activity was significantly increased by both flutamide and bicalutamide. Furthermore, these drugs decreased CTL1 expression in the prostate cancer cell line. These results suggest that CTL1 is functionally expressed in prostate cancer cells and are also involved in abnormal proliferation. Identification of this CTL1-mediated choline transport system in prostate cancer cells provides a potential new therapeutic target for the treatment of this disease.

• Nutrition Research and Practice
• /
• v.4 no.6
• /
• pp.462-469
• /
• 2010

Protamine has been widely used as a pharmaceutical product and natural food preservative. However, few studies have been conducted to assess the beneficial function of dietary protamine. This study examined the effects of dietary salmon protamine on serum and liver lipid levels and the expression levels of genes encoding proteins involved in lipid homeostasis in the liver of rats. Groups of male Wistar rats were fed AIN93G diet containing 2% or 5% protamine. After 4 weeks of feeding these diets, markedly decreased serum and liver cholesterol (CHOL) and triacylglycerol levels were noted. Increased activity of liver carnitine palmitoyltransferase-2 and acyl-CoA oxidase, which are key enzymes of fatty acid ${\beta}$-oxidation in the mitochondria and peroxisomes, was found in rats fed on protamine. Furthermore, rats fed protamine showed enhanced fecal excretion of CHOL and bile acid and increased liver mRNA expression levels of ATP-binding cassette (ABC) G5 and ABCG8, which form heterodimers and play a major role in the secretion of CHOL into bile. The decrease in triacylglycerol levels in protamine-fed rats was due to the enhancement of liver ${\beta}$-oxidation. Furthermore, rats fed protamine exhibited decreased CHOL levels through the suppression of CHOL and bile acid absorption and the enhancement of CHOL secretion into bile. These results suggest that dietary protamine has beneficial effects that may aid in the prevention of lifestyle-related diseases such as hyperlipidemia and atherosclerosis.

• BMB Reports
• /
• v.32 no.6
• /
• pp.585-593
• /
• 1999

The water and methanol extracts of Artemisia argyi showed significant cytotoxicities against J774A.1 cells but not so much against normal leukocytes. The cytotoxicities were found to be dependent on the extract concentration and the incubation time. The concentration of water and methanol extracts inhibiting 50% of cell proliferation ($IC_{50}$) were estimated to be 44.2 mg/ml and 71.6 mg/ml, respectively. In the presence of Artemisia argyi water extract, total superoxide dismutase (CuZnSOD and MnSOD) activities of media, cytoplasmic and mitochondrial fractions of J774A.1 cells increased in accordance with cytotoxicity. MnSOD was found to be the main component of enhanced total SOD activities, particulary in the mitochondrial fraction. In contrast to SOD, catalase and glutathione peroxidase (GPx) were not found in any instance of the current investigation. In addition, substantial amount of $O_2^-$ appeared to be generated in the mitochondrial fraction under the influence of Artemisia argyi. All data put together, it is postulated that Artemisia argyi extracts seem to stimulate $O_2^-$ generation in mitochondria of J774A.1 cells with concomitant increases of SODs. Since $H_2O_2$, the reaction product of SOD on $O_2^-$, is known to be readily converted to very toxic $OH{\cdot}$ in the absence of catalase and/or GPx cooperation, toxicity derived from ROS such as $O_2^-$, $H_2O_2$, and $OH{\cdot}$ may be the main cause of necrosis and/or apoptosis of J774A.1 cells.

• Journal of Nutrition and Health
• /
• v.33 no.7
• /
• pp.725-732
• /
• 2000

The purpose of this study was to investigate the effects of green tea catechin on renal dysfunction and blood presure change in chronic cadmium poisoned rats. Sprague-Dawley male rats weighing 100$\pm$10g were randomly assigned to one normal group and three cadmium poisoned groups. Cadmium groups were classified to catechin free diet(Cd-0C group) 0.25% catechin diet(Cd-0.25C group) and 0.5% catechin diet(Cd-0.5C group) according to the levels of catechin supplement. Animals were raids for 20weeks. Cadmium were supplied as drinking water of 50ppm Cd2+ Morphological changes shown through a light microscope and an electro-microscope revealed the mitochondria and tubule epithelial cell edema in Cd -0C group but they were alleviated in catechin supplementation. The urinary $\beta$2-microglobulin that measured to observe the glomerular injury were higher in Cd-poisoned groups than in normal group but they was lowered by catechin supplementation. Glomerular filtration ratios(GFR) in Cd-poisoned groups were significantly lower than in normal group but that of catechin supplementation group was similar to normal group. This suggested that catechin protected the kidney from the functional damage. Angiotensin converting enzyme(ACE) activity and blood pressure(BP) in Cd-poisoned groups were significantly higher than in normal group. Heart rate was tended to increase in Cd-poisoned groups. The results indicate that green tea catechin supplementation on chronic cadmium-poisoned rats normalized the renal dysfunction and blood pressure system.

• Development and Reproduction
• /
• v.14 no.2
• /
• pp.75-82
• /
• 2010

The objective of this study is to identify the effects of endurance exercise and selenium on mitochondrial transcription factor in old Goto-Kakizaki (GK) rats. In this experiments, endurance exercise were treadmill-run at 24 m/min, 30 min/day, 5 days/week, 6 weeks and 5 umol/kg of sodium selenite was injected intraperitoneally. In exercise group, selenium group, and combination group, the mitohondrial biogenesis-related genes, including PGC-$1{\alpha}$, NRF-1, and Tfam expression level were significantly increased compared to control group. Consistent with the increased biogenesis-related genes, the cytochrome C in the treated groups, which was the indicator of mitochondrial content, was significantly increased compared to control group. Especially, combination of exercise and selenium may be effective in the increase of mitochondrial biogenesis, activity and insulin sensitivity. Therefore, exercise and selenium treatment is likely to promote diabeticmitochondrial malfunction and then improve diabetes.

• Journal of Microbiology and Biotechnology
• /
• v.16 no.1
• /
• pp.84-91
• /
• 2006

A Saccharomyces cerevisiae pgs1 nulI mutant, which is deficient with phosphatidyl glycerol (PG) and cardiolipin (CL) biosynthesis, grows well on most fermentable carbon sources, but fails to grow on non-fermentable carbon sources such as glycerol, ethanol, and lactate. This mutant also cannot grow on galactose medium as the sole carbon source. We found that the incorporation of $[^{14}C]-galactose$, which is the first step of the galactose metabolic pathway (Leloir pathway), into the pgs 1 null mutant cell was extremely repressed. Exogenously expressed PGS1 (YCpPGS1) under indigenous promoter could completely restore the pgs1 growth defect on non-fermentable carbon sources, and dramatically recovered $[^{14}C]-galactose$ incorporation into the pgs1 mutant cell. However, PGS1 expression under the GALl promoter $(YEpP_{GAL1}-PGS1myc)$ could not complement pgs1 mutation, and the GAL2-lacZ fusion gene $(YEpP_{GAL2}-lacZ)$ also did not exhibit its $\beta-galactosidase$ activity in the pgs1 mutant. In wild-type yeast, antimycin $A(1\;{\mu}g/ml)$, which inhibits mitochondrial complex III, severely repressed not only the expression of the GAL2-lacZ fusion gene, but also uptake of $[^{14}C]-galactose$. However, exogenously expressed PGS1 partially relieved these inhibitory effects of antimycin A in both the pgs1 mutant and wild-type yeast, although it could not basically restore the growth defect on galactose by antimycin A. These results suggest that the PGSI gene product has an important role in utilization of galactose by Gal genes, and that intact mitochondrial function with PGS1 should be required for galactose incorporation into the Leloir pathway. The PGS1 gene might provide a clue to resolve the historic issue about the incapability of galactose with deteriorated mitochondrial function.

• The Korean Journal of Physiology and Pharmacology
• /
• v.24 no.3
• /
• pp.223-232
• /
• 2020

Sesamin, a lipid-soluble lignin originally isolated from sesame seeds, which induces cancer cell apoptosis and autophagy. In the present study, has been reported that sesamin induces apoptosis via several pathways in human lung cancer cells. However, whether mitophagy is involved in sesamin induced lung cancer cell apotosis remains unclear. This study, the anticancer activity of sesamin in lung cancer was studied by reactive oxygen species (ROS) and mitophagy. A549 cells were treated with sesamin, and cell viability, migration ability, and cell cycle were assessed using the CCK8 assay, scratch-wound test, and flow cytometry, respectively. ROS levels, mitochondrial membrane potential, and apoptosis were examined by flow cytometric detection of DCFH-DA fluorescence and by using JC-1 and TUNEL assays. The results indicated that sesamin treatment inhibited the cell viability and migration ability of A549 cells and induced G₀/G₁ phase arrest. Furthermore, sesamin induced an increase in ROS levels, a reduction in mitochondrial membrane potential, and apoptosis accompanied by an increase in cleaved caspase-3 and cleaved caspase-9. Additionally, sesamin triggered mitophagy and increased the expression of PINK1 and translocation of Parkin from the cytoplasm to the mitochondria. However, the antioxidant N-acetyl-L-cysteine clearly reduced the oxidative stress and mitophagy induced by sesamin. Furthermore, we found that cyclosporine A (an inhibitor of mitophagy) decreased the inhibitory effect of sesamin on A549 cell viability. Collectively, our data indicate that sesamin exerts lethal effects on lung cancer cells through the induction of ROS-mediated mitophagy and mitochondrial apoptosis.

• The Korean Journal of Physiology and Pharmacology
• /
• v.24 no.3
• /
• pp.249-257
• /
• 2020

The aim of the present study was to investigate the pathophysiological etiology of osteoarthritis that is mediated by the apoptosis of chondrocytes exposed to 25-hydroxycholesterol (25-HC), an oxysterol synthesized by the expression of cholesterol-25-hydroxylase (CH25H) under inflammatory conditions. Interleukin-1β induced the apoptosis of chondrocytes in a dose- dependent manner. Furthermore, the production of 25-HC increased in the chondrocytes treated with interleukin-1β through the expression of CH25H. 25-HC decreased the viability of chondrocytes. Chondrocytes with condensed nucleus and apoptotic populations increased by 25-HC. Moreover, the activity and expression of caspase-3 were increased by the death ligand-mediated extrinsic and mitochondria-dependent intrinsic apoptotic pathways in the chondrocytes treated with 25-HC. Finally, 25-HC induced not only caspase-dependent apoptosis, but also induced proteoglycan loss in articular cartilage ex vivo cultured rat knee joints. These data indicate that 25-HC may act as a metabolic pathophysiological factor in osteoarthritis that is mediated by progressive chondrocyte death in the articular cartilage with inflammatory condition.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.6
• /
• pp.697-703
• /
• 2018

Myoblast fusion depends on mitochondrial integrity and intracellular $Ca^{2+}$ signaling regulated by various ion channels. In this study, we investigated the ionic currents associated with $[Ca^{2+}]_i$ regulation in normal and mitochondrial DNA-depleted(${\rho}0$) L6 myoblasts. The ${\rho}0$ myoblasts showed impaired myotube formation. The inwardly rectifying $K^+$ current ($I_{Kir}$) was largely decreased with reduced expression of KIR2.1, whereas the voltage-operated $Ca^{2+}$ channel and $Ca^{2+}$-activated $K^+$ channel currents were intact. Sustained inhibition of mitochondrial electron transport by antimycin A treatment (24 h) also decreased the $I_{Kir}$. The ${\rho}0$ myoblasts showed depolarized resting membrane potential and higher basal $[Ca^{2+}]_i$. Our results demonstrated the specific downregulation of $I_{Kir}$ by dysfunctional mitochondria. The resultant depolarization and altered $Ca^{2+}$ signaling might be associated with impaired myoblast fusion in ${\rho}0$ myoblasts.

• The Korean Journal of Malacology
• /
• v.32 no.1
• /
• pp.17-23
• /
• 2016

Ultrastructural studies of oocyte development and vitellogenesis associated with the follicle cells in female Phacosoma japonicus were investigated by electron microscope observations. Vitelloogenesis in the oocytes occured by way of endogenous autosynthesis and exogenous heterosynthesis: vitellogenesis occurred through a process of endogenous autosynthesis, which involves a combined activity of the Golgi complex, rough endoplasmic reticulum, and mitochondria. However, the process of exogenous heterosynthesis involved endocytotic incorporation of extraovarian precursors into the basal region of the early vitellogenic oocytes. In this study, follicle cells, which attached to the previtellogenic and vitellogenic oocytes, were easily found. In particular, the follicle cells were involved in the development of previtellogenic oocytes by the supply of nutrients, and vitellogenesis in the early and late vitellogenic oocytes by endocytosis of yolk precursors. The functions of follicle cells, which attached to mature oocytes, accumulate reserves of lipid granules and glycogen particles for vitellogesis in the cytoplasm of the follicle cells.