• 약학회지
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• 제55권3호
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• pp.251-259
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• 2011

Cigarette smoke condensate (CSC) is known to be carcinogenic compound. CSC contains many organic compounds such as polycyclic aromatic hydrocarbons (PAHs), and heterocyclic amine compounds (HCAs). Reactive oxygen species (ROS) are also generated and induce oxidative DNA damage during the metabolism of CSC. The rat microsome mediated and DNA repair enzyme treated comet assays together with conventional comet assay were performed to evaluate the mechanisms of CSC genotoxicity. The organic extract of CSC induced oxidative and microsome mediated DNA damage. Vitamin C as a model antioxidant reduced DNA damage in endonuclease III treated comet assay. One of flavonoid, galangin as a CYP1A1 inhibitor, reduced DNA damage in the presence of S-9 mixture. The ethanol extracts of the mixed vegetables (BV) or the mixed fruits (BF) showed potent inhibitory effects against CSC induced DNA damage with oxidative DNA lesions and in the prescence of S-9 mixture. These results indicate that BV and BF could prevent CSC-induced cellular DNA damage by inhibiting oxidative stress and suppressing cytochrome P450 in mammalian cells.

• Molecules and Cells
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• 제37권6호
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• pp.441-448
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• 2014

Inflammasomes are specialized signaling platforms critical for the regulation of innate immune and inflammatory responses. Various NLR family members (i.e., NLRP1, NLRP3, and IPAF) as well as the PYHIN family member AIM2 can form inflammasome complexes. These multiprotein complexes activate inflammatory caspases (i.e., caspase-1) which in turn catalyze the maturation of select pro-inflammatory cytokines, including interleukin (IL)-$1{\beta}$ and IL-18. Activation of the NLRP3 inflammasome typically requires two initiating signals. Toll-like receptor (TLR) and NOD-like receptor (NLR) agonists activate the transcription of pro-inflammatory cytokine genes through an NF-${\kappa}B$-dependent priming signal. Following exposure to extracellular ATP, stimulation of the P2X purinoreceptor-7 ($P2X_7R$), which results in $K^+$ efflux, is required as a second signal for NLRP3 inflammasome formation. Alternative models for NLRP3 activation involve lysosomal destabilization and phagocytic NADPH oxidase and /or mitochondria-dependent reactive oxygen species (ROS) production. In this review we examine regulatory mechanisms that activate the NLRP3 inflammasome pathway. Furthermore, we discuss the potential roles of NLRP3 in metabolic and cognitive diseases, including obesity, type 2 diabetes mellitus, Alzheimer's disease, and major depressive disorder. Novel therapeutics involving inflammasome activation may result in possible clinical applications in the near future.

• The Korean Journal of Physiology
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• 제19권2호
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• pp.155-160
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• 1985

Dantrolene sodium(DS) is a long acting skeletal muscle relaxant which has been successfully used to control muscle spasticity in patients with various neurological disorders. However, its use is associated with hepatotoxicity. Tissue sulfhydryl group has many important roles for cellular integration and glutathione serves as a substrate for the detoxification metabolism. The purpose of this study were to investigate the effect of DS on tissue sulfhydrl group and glutathione content. Foully albino rats were divided into two groups ; saline treated (control) and DS treated groups. DS dissolved in saline was administered orally. All rats were sacrificed after 7. 14. 21 and 28 days of DS ana saline treatment by dacapitation ana liver was removed for the enzyme preparation. Total and nonprotein sulfhydryl were measured by the method of Sedlak and Lindsay (1968). Total glutathione content was assayed according to the method described by Tietze (1969) and glutathione reductase was assayed according to the method of Racker (1955), The results obtained are summarized as follows : DS administration significantly depressed the total, protein and nonprotein sulfhydryl content in liver. There were significant reduction of both total glutathione content and glutathione reductase activity in liver. On the basis of the above results it may be speculated that the toxicity of DS are well correlated with tissue sulfhydryl content and glutathione reductase activity.

• Journal of Microbiology and Biotechnology
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• 제9권4호
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• pp.404-413
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• 1999

Methanopyrus kandleri is a hyperthermophilic methanogen that represents one of the most heat-resistant organisms: the maximum growth temperature of M. kandleri is $110^{\circ}C$. A random sequence analysis of the genomic DNA of M. kandleri has been performed to obtain genomic information. More than 200 unique sequence tags were obtained and compared with the sequences in the GenBank and PIR databases. About 30% of the analyzed tags showed strong sequence similarity to previously identified genes involved in various cellular processes such as biosynthesis, transport, methanogenesis, or metabolism. When statistics relating to the frequency of codons were examined, the sequenced open reading frames showed highly biased codon usage and a high content of charged amino acids. Among the identified genes, a homologue of the catalytic subunit of carbon monoxide dehydrogenase (CODH) that reduces $CO_2$ to CO was cloned and sequenced in order to examine its detailed gene structure. The cloned gene includes consensus promoters. The amino acid sequence of the cloned gene shows a strong homology with the CODH genes from methanogenic Archaea, especially in the presumed binding sites for Fe-S centers.

• Journal of Community Nutrition
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• 제7권2호
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• pp.79-84
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• 2005

A vitamin B-6 (B-6) intake higher than the current Recommended Dietary Allowance (RDA) has been found to provide an improvement in immune system. Seven premenopausal women consumed their usual diet with the exception of foods relatively high in vitamin B-6 for a total of 27 d. After 7 d, all subjects received a multivitamin supplement containing 2mg B-6 and 4 subjects were given an additional 50mg of B-6 supplement for 20 d. Lymphocyte response to phytohemagglutinin (PHA) was measured before and after the supplementation. To determine the effect of different forms of B-6 on lymphocyte proliferation, cell culture media supplemented with pyridoxal (PL) and PLP, as well as B-6 free media, were tested. A 50mg B-6 supplement significantly increased vitamin B-6 status. There was no further enhancement on lymphocyte proliferation when subjects were taking an additional 50mg of vitamin B-6 supplement. In general, lymphocyte proliferation in media with either PLP or PL did not show any prominent difference. These [m-dings suggest that there may be no further benefits of a B-6 dose beyond twice that of the current RDA on lymphocyte proliferation. Further studies are necessary to examine the effect of the B-6 intake level on activities of enzymes involved in cellular B-6 metabolism in lymphocytes to provide substantial insight into the mechanisms underlying the role of B-6 in the lymphocyte proliferation.

• BMB Reports
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• 제47권7호
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• pp.361-368
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• 2014

Lipid components in biological membranes are essential for maintaining cellular function. Phosphoinositides, the phosphorylated derivatives of phosphatidylinositol (PI), regulate many critical cell processes involving membrane signaling, trafficking, and reorganization. Multiple metabolic pathways including phosphoinositide kinases and phosphatases and phospholipases tightly control spatio-temporal concentration of membrane phosphoinositides. Metabolizing enzymes responsible for PI 4,5-bisphosphate (PI(4,5)P2) production or degradation play a regulatory role in Toll-like receptor (TLR) signaling and trafficking. These enzymes include PI 4-phosphate 5-kinase, phosphatase and tensin homolog, PI 3-kinase, and phospholipase C. PI(4,5)P2 mediates the interaction with target cytosolic proteins to induce their membrane translocation, regulate vesicular trafficking, and serve as a precursor for other signaling lipids. TLR activation is important for the innate immune response and is implicated in diverse pathophysiological disorders. TLR signaling is controlled by specific interactions with distinct signaling and sorting adaptors. Importantly, TLR signaling machinery is differentially formed depending on a specific membrane compartment during signaling cascades. Although detailed mechanisms remain to be fully clarified, phosphoinositide metabolism is promising for a better understanding of such spatio-temporal regulation of TLR signaling and trafficking.

• Journal of Acupuncture Research
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• 제22권2호
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• pp.83-92
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• 2005

Objective: Although the effect of Ulmus davidiana Planch (UD) extracts on collagen-induced-arthritis (CIA) and bone metabolism has been studies, research on its effect on human immunomodulatory activity is further a due. The objective of the present study was to investigate the immunomodulatory activity of UD on cellular and humoral immunity. Methods : Oral administration of the ethanolic and water extracts of UD, at doses of 20, 100 and 200 mg/kg in mice, dose dependently potentiated the delayed type hypersensitivity reaction induced both by sheep red blood cells (SRBC) and oxazolone. Results : It significantly enhanced the production of circulating antibody titre in response to SRBC in mice. Extracts of UD failed to show any effect on macrophage phagocytosis. Chronic administration of UD extracts significantly ameliorated the total white blood cell count and also restored the myelosuppressive effects induced by cyclophosphamide. Conclusion : The present investigation reveals that UD extracts possesses immunomodulatory activity.

• Journal of Ginseng Research
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• 제21권1호
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• pp.1-12
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• 1997

Ginseng, the root of Panax ginseng C.A. Meyer, is well-known oriental herbal medicine. The number of paper reporting the effects on its physiological, pharmacological, and behavioral effects has been increased every year, since ginsenosides isolated from ginseng are known to be biologically active components. This brief review summarizes some of new findings from recently published papers on ginsenosides or ginseng saponins. Therefore, this paper includes the various effects of ginsenosides on neuronal cell growths, on behavior of experimental animals, on enzyme activities, on the release and uptake of neurotransmitters, on neuronal cell excitability, on the motility of intestine, on antitumor activity, on cardiovascular system and metabolism. In spite of various effects of ginsenosides on various cells or organs, it is still to date impossible for one to clearly explain the exact mechanism on the action of ginsenosides. However, in this article I will discuss several papers providing possible explanations on the physiological and pharmacological actions including signal transudation pathway of ginsenosides. The elucidation of the exact mechanism of ginsenosides on cellular or molecular level will not only give us a chance to explain why people have used ginseng as an elixir of life for several thousands of year but also give us a crucial chance to apply ginseng to modern medicine.

• Molecules and Cells
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• 제22권3호
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• pp.275-284
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• 2006

The molecular components that generate and maintain circadian rhythms of physiology and behavior in mammals are present both in the brain (suprachiasmatic nucleus; SCN) and in peripheral tissues. Examination of mice with targeted disruptions of either mPer1 or mPer2 has shown that these two genes have key roles in the SCN circadian clock. Here we show that loss of the clock gene mPer2 affects forced locomotor performance in mice without altering muscle contractility. A proteomic analysis revealed that the anterior tibialis muscles of the mPer2 knockout mice had higher levels of glycolytic enzymes such as triose phosphate isomerase and enolase than those of either the wild type or mPer1 knockout mice. In addition, the level of expression of HSP90 in the mPer2 mutant mice was also significantly higher than in wildtype mice. These results suggest that the reduced locomotor endurance of the mPer2 knockout mice reflects a greater dependence on anaerobic metabolism under stress conditions, and that the two canonical clock genes, mPer1 and mPer2, play distinct roles in the physiology of skeletal muscle.

• Molecules and Cells
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• 제39권4호
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• pp.358-366
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• 2016

The digestive system is gaining interest as a major regulator of various functions including immune defense, nutrient accumulation, and regulation of feeding behavior, aside from its conventional function as a digestive organ. The Drosophila midgut epithelium is completely renewed every 1-2 weeks due to differentiation of pluripotent intestinal stem cells in the midgut. Intestinal stem cells constantly divide and differentiate into enterocytes that secrete digestive enzymes and absorb nutrients, or enteroendocrine cells that secrete regulatory peptides. Regulatory peptides have important roles in development and metabolism, but study has mainly focused on expression and functions in the nervous system, and not much is known about the roles in endocrine functions of enteroendocrine cells. We systemically examined the expression of 45 regulatory peptide genes in the Drosophila midgut, and verified that at least 10 genes are expressed in the midgut enteroendocrine cells through RT-PCR, in situ hybridization, antisera, and 25 regulatory peptide-GAL transgenes. The Drosophila midgut is highly compartmentalized, and individual peptides in enteroendocrine cells were observed to express in specific regions of the midgut. We also confirmed that some peptides expressed in the same region of the midgut are expressed in mutually exclusive enteroendocrine cells. These results indicate that the midgut enteroendocrine cells are functionally differentiated into different subgroups. Through this study, we have established a basis to study regulatory peptide functions in enteroendocrine cells as well as the complex organization of enteroendocrine cells in the Drosophila midgut.