• Nutrition Research and Practice
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• v.3 no.2
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• pp.77-83
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• 2009

Retinoic acids (RAs) modulate growth, differentiation, and apoptosis in normal, pre-malignant & malignant cells. In the present study, the effects of RA isomers (all-trans RA, 13-cis RA, and 9-cis RA) on the cell signal transduction of human breast cancer cells have been studied. The relationship between RAs and an enzymatic antioxidant system was also determined. Estrogen-receptor (ER) positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells were treated with different doses of each RA isomers, all-trans RA, 13-cis RA, or 9-cis RA. Treatment of RA isomers inhibited cell viability and induced apoptosis of MCF-7 cells as a result of increased caspase activity in cytoplasm and cytochrome C released from mitochondria. All-trans RA was the most effective RA isomer in both cell growth inhibition and induction of apoptosis in MCF-7 cells. However, no significant effect of RA isomers was observed on the cell growth or apoptosis in ER-negative MDA-MB-231 cells. In addition, activities of antioxidant enzymes such as catalase and glutathione peroxidase were decreased effectively after treatment of RA in MCF-7 cells, whereas SOD activity was rarely affected. Thus, the present data suggest that all-trans RA is the most potential inducer of apoptosis and modulator of antioxidant enzymes among RA isomers in MCF-7 human breast cancer cells.

• 대한약리학회:학술대회논문집
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• 2006.11a
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• pp.41-41
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• 2006

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.483-489
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• 2009

Despite the potential importance of the human regulator of calcineurin 1 (RCAN-1) gene in the modulation of cell survival under stress, little is known about its role in death-inducing signal pathways. In this study, we addressed the effects of RCAN1.4 knockdown on cellular susceptibility to apoptosis and the activation of death pathway proteins. Transfection of siRNAs against RCAN1.4 resulted in enhanced Fas- and etoposide-induced apoptosis, which was associated with increased expression and translocation of Bax to mitochondria. Our results suggest that enhanced expression and activation of p53 was responsible for the upregulation of Bax and the increased sensitivity to apoptosis, which could be reversed by p53 knockdown. To explain the observed upregulation of p53, we propose a downregulation of the ubiquitin ligase HDM2, probably translationally. These findings show the importance of appropriate RCAN1.4 expression in the modulation of cell survival and reveal a link between RCAN1.4 and p53.

• Archives of Pharmacal Research
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• v.27 no.8
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• pp.867-872
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• 2004

Oxidative stress due to reactive oxygen species (ROS) can cause oxidative damage to cells. Cells have a number of defense mechanisms to protect themselves from the toxicity of ROS. Mitochondria are especially important in the oxidative stress as ROS have been found to be constantly generated as an endogen threat. Mitochondrial defense depends mainly on super-oxide dismutase (SOD) and glutathione peroxidase (GPx), whereas microsomal defense depends on catalase (CAT), which is an enzyme abundant in microsomes. SOD removes superoxide anions by converting them to $H_2O$$_2$, which can be rapidly converted to water by CAT and GPx. Also, GPx converts hydroperoxide (ROOH) into oxidized-glutathione (GSSG). Ovariectomized (OVX) rats are used as an oxidative stress model. An ovariectomy increased the levels of MDA, one of the end-products in the lipid peroxidative process, and decreased levels of the antioxidative enzymes； SOD, CAT and GPx. However, Chondroitin sulfate (CS) decreased the levels of MDA, but increased the levels of SOD, CAT and GPx in a dose-depen-dent manner. Moreover, inflammation and cirrhosis of liver tissue in CS- treated rats were sig-nificantly decreased. These results suggest that CS might be a potential candidate as an anti oxidative reagent.

• IMMUNE NETWORK
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• v.14 no.2
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• pp.116-122
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• 2014

Macrophage death plays a role in several physiological and inflammatory pathologies such as sepsis and arthritis. In our previous work, we showed that simvastatin triggers cell death in LPS-activated RAW 264.7 mouse macrophage cells through both caspase-dependent and independent apoptotic pathways. Here, we show that the nuclear orphan receptor NR4A1 is involved in a caspase-independent apoptotic process induced by LPS and simvastatin. Simvastatin-induced NR4A1 expression in RAW 264.7 macrophages and ectopic expression of a dominant-negative mutant form of NR4A1 effectively suppressed both DNA fragmentation and the disruption of mitochondrial membrane potential (MMP) during LPS- and simvastatin-induced apoptosis. Furthermore, apoptosis was accompanied by Bcl-2-associated X protein (Bax) translocation to the mitochondria. Our findings suggest that NR4A1 expression and mitochondrial translocation of Bax are related to simvastatin-induced apoptosis in LPS-activated RAW 264.7 macrophages.

• BMB Reports
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• v.47 no.1
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• pp.15-20
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• 2014

Intracellular lipid-binding proteins (LBPs) impact fatty acid homeostasis in various ways, including fatty acid transport into mitochondria. However, the physiological consequences caused by mutations in genes encoding LBPs remain largely uncharacterized. Here, we explore the metabolic consequences of lbp-5 gene deficiency in terms of energy homeostasis in Caenorhabditis elegans. In addition to increased fat storage, which has previously been reported, deletion of lbp-5 attenuated mitochondrial membrane potential and increased reactive oxygen species levels. Biochemical measurement coupled to proteomic analysis of the lbp-5(tm1618) mutant revealed highly increased rates of glycolysis in this mutant. These differential expression profile data support a novel metabolic adaptation of C. elegans, in which glycolysis is activated to compensate for the energy shortage due to the insufficient mitochondrial ${\beta}$-oxidation of fatty acids in lbp-5 mutant worms. This report marks the first demonstration of a unique metabolic adaptation that is a consequence of LBP-5 deficiency in C. elegans.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3073-3076
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• 2012

Terpinen-4-ol is a terpene found in the rhizome of Plai (Zingiber montanum (Koenig) Link ex Dietr.). In this study apoptogenic activity and mechanisms of cell death induced by terpinen-4-ol were investigated in the human leukemic MOLT-4 cell line. Terpinen-4-ol exhibited cytotoxicity in MOLT-4 cells, with characteristic morphological features of apoptosis by Wright's staining. The mode of cell death was confirmed to be apoptosis by flow cytometric analysis after staining with annexin V-FITC and propidium iodide. A sub-G1 peak in DNA histograms of cell cycle assays was observed. Terpinen-4-ol induced-MOLT-4 cell apoptosis mediated through an intrinsic pathway involving the loss of mitochondrial transmembrane potential (MTP) and release of cytochrome c into the cytosol. In addition, terpinen-4-ol also induced apoptosis via an extrinsic pathway by caspase-8 activation resulting in the cleavage of cytosolic Bid. Truncated-Bid (tBid) translocated to mitochondria and activated the mitochondrial pathway in conjunction with down-regulation of Bcl-2 protein expression. Caspase-3 activity also increased. In conclusion, terpinen-4-ol can induce human leukemic MOLT-4 cell apoptosis via both intrinsic and extrinsic pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6321-6326
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• 2014

${\alpha}$-Methyl-n-butylshikonin (MBS), one of the active components in the root extracts of Lithospermum erythrorhizon, posses antitumor activity. In this study, we assess the molecular mechanisms of MBS in causing apoptosis of SW620 cells. MBS reduced the cell viability of SW620 cells in a dose-and time-dependent manner and induced cell apoptosis. Treatment of SW620 cells with MBS down-regulated the expression of Bcl-2 and up-regulated the expression of Bak and caused the loss of mitochondrial membrane potential. Additionally, MBS treatment led to activation of caspase-9, caspase-8 and caspase-3, and cleavage of PARP, which was abolished by pretreatment with the pan-caspase inhibitor Z-VAD-FMK. MBS also induced significant elevation in the phosphorylation of JNK and p38. Pretreatment of SW620 cells with specific inhibitors of JNK (SP600125) and p38 (SB203580) abrogated MBS-induced apoptosis. Our results demonstrated that MBS inhibited growth of colorectal cancer SW620 cells by inducing JNK and p38 signaling pathway, and provided a clue for preclinical and clinical evaluation of MBS for colorectal cancer therapy.

• Asian-Australasian Journal of Animal Sciences
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• v.17 no.5
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• pp.726-732
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• 2004

In this manuscript, a review of the diversity of Chinese indigenous goat breeds according to data from body stature and appearance, chromosome group, blood proteins, DNA molecular markers (mitochondria DNA, random amplified polymorphic DNA, microsatellite DNA, major histocompatibility complex) has been introduced. All of these provide efficient tools for the diversity analysis of Chinese indigenous goat breeds and are very important for biodiversity conservation, restoration of declining goat breeds, the priority defining in Chinese indigenous goat breeds' protection and the selection of nature preservation zones. Many Chinese indigenous goat breeds with small population size in the isolated mountains or reservoir areas are verging the potential threat of extinction, effectively lost with the rapid destroying of ecological environment. On the other hand, as a result of the introduction of modern commercial goat breeds and shortage of effective conservation, some populations, such as Small-xiang goat and Tibetan goat decrease rapidly in number of sires. In the interests of the long-term future of the goat breeds in China, conservation of goat breeds' genetic resources should be considered urgently and some conservation measures should be adopted. In addition, the continuing development of molecular biology will further enhance conservation of diversity of Chinese indigenous goat breeds.

• BMB Reports
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• v.46 no.8
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• pp.391-397
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• 2013

The ATP-inhibited Plant Mitochondrial $K^+$ Channel ($PmitoK_{ATP}$) was discovered about fifteen years ago in Durum Wheat Mitochondria (DWM). $PmitoK_{ATP}$ catalyses the electrophoretic $K^+$ uniport through the inner mitochondrial membrane; moreover, the co-operation between $PmitoK_{ATP}$ and $K^+/H^+$ antiporter allows such a great operation of a $K^+$ cycle to collapse mitochondrial membrane potential (${\Delta}{\Psi}$) and ${\Delta}pH$, thus impairing protonmotive force (${\Delta}p$). A possible physiological role of such ${\Delta}{\Psi}$ control is the restriction of harmful reactive oxygen species (ROS) production under environmental/oxidative stress conditions. Interestingly, DWM lacking ${\Delta}p$ were found to be nevertheless fully coupled and able to regularly accomplish ATP synthesis; this unexpected behaviour makes necessary to recast in some way the classical chemiosmotic model. In the whole, $PmitoK_{ATP}$ may oppose to large scale ROS production by lowering ${\Delta}{\Psi}$ under environmental/oxidative stress, but, when stress is moderate, this occurs without impairing ATP synthesis in a crucial moment for cell and mitochondrial bioenergetics.