• Title/Summary/Keyword: Species abundance

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Induction of Phase I, II and III Drug Metabolism/Transport by Xenobiotics

  • Xu Chang Jiang;Li Christina YongTao;Kong AhNg Tony
    • Archives of Pharmacal Research
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    • v.28 no.3
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    • pp.249-268
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    • 2005
  • Drug metabolizing enzymes (DMEs) play central roles in the metabolism, elimination and detoxification of xenobiotics and drugs introduced into the human body. Most of the tissues and organs in our body are well equipped with diverse and various DMEs including phase I, phase II metabolizing enzymes and phase III transporters, which are present in abundance either at the basal unstimulated level, and/or are inducible at elevated level after exposure to xenobiotics. Recently, many important advances have been made in the mechanisms that regulate the expression of these drug metabolism genes. Various nuclear receptors including the aryl hydrocarbon receptor (AhR), orphan nuclear receptors, and nuclear factor-erythoroid 2 p45-related factor 2 (Nrf2) have been shown to be the key mediators of drug-induced changes in phase I, phase II metabolizing enzymes as well as phase III transporters involved in efflux mechanisms. For instance, the expression of CYP1 genes can be induced by AhR, which dimerizes with the AhR nuclear translocator (Arnt) , in response to many polycyclic aromatic hydrocarbon (PAHs). Similarly, the steroid family of orphan nuclear receptors, the constitutive androstane receptor (CAR) and pregnane X receptor (PXR), both heterodimerize with the ret-inoid X receptor (RXR), are shown to transcriptionally activate the promoters of CYP2B and CYP3A gene expression by xenobiotics such as phenobarbital-like compounds (CAR) and dexamethasone and rifampin-type of agents (PXR). The peroxisome proliferator activated receptor (PPAR), which is one of the first characterized members of the nuclear hormone receptor, also dimerizes with RXR and has been shown to be activated by lipid lowering agent fib rate-type of compounds leading to transcriptional activation of the promoters on CYP4A gene. CYP7A was recognized as the first target gene of the liver X receptor (LXR), in which the elimination of cholesterol depends on CYP7A. Farnesoid X receptor (FXR) was identified as a bile acid receptor, and its activation results in the inhibition of hepatic acid biosynthesis and increased transport of bile acids from intestinal lumen to the liver, and CYP7A is one of its target genes. The transcriptional activation by these receptors upon binding to the promoters located at the 5-flanking region of these GYP genes generally leads to the induction of their mRNA gene expression. The physiological and the pharmacological implications of common partner of RXR for CAR, PXR, PPAR, LXR and FXR receptors largely remain unknown and are under intense investigations. For the phase II DMEs, phase II gene inducers such as the phenolic compounds butylated hydroxyanisol (BHA), tert-butylhydroquinone (tBHQ), green tea polyphenol (GTP), (-)-epigallocatechin-3-gallate (EGCG) and the isothiocyanates (PEITC, sul­foraphane) generally appear to be electrophiles. They generally possess electrophilic-medi­ated stress response, resulting in the activation of bZIP transcription factors Nrf2 which dimerizes with Mafs and binds to the antioxidant/electrophile response element (ARE/EpRE) promoter, which is located in many phase II DMEs as well as many cellular defensive enzymes such as heme oxygenase-1 (HO-1), with the subsequent induction of the expression of these genes. Phase III transporters, for example, P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), and organic anion transporting polypeptide 2 (OATP2) are expressed in many tissues such as the liver, intestine, kidney, and brain, and play crucial roles in drug absorption, distribution, and excretion. The orphan nuclear receptors PXR and GAR have been shown to be involved in the regulation of these transporters. Along with phase I and phase II enzyme induction, pretreatment with several kinds of inducers has been shown to alter the expression of phase III transporters, and alter the excretion of xenobiotics, which implies that phase III transporters may also be similarly regulated in a coordinated fashion, and provides an important mean to protect the body from xenobiotics insults. It appears that in general, exposure to phase I, phase II and phase III gene inducers may trigger cellular 'stress' response leading to the increase in their gene expression, which ultimately enhance the elimination and clearance of these xenobiotics and/or other 'cellular stresses' including harmful reactive intermediates such as reactive oxygen species (ROS), so that the body will remove the 'stress' expeditiously. Consequently, this homeostatic response of the body plays a central role in the protection of the body against 'environmental' insults such as those elicited by exposure to xenobiotics.

The Change of Phytoplankton Community Structure and Water Quality in the Juksan Weir of the Yeongsan River Watershed (영산강수계 죽산보의 식물플랑크톤과 이화학적 변화)

  • Son, Misun;Chung, Hyeon Su;Park, Chang Hee;Park, Jong-hwan;Lim, Cheahong;Kim, Kyunghyun
    • Korean Journal of Environmental Biology
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    • v.36 no.4
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    • pp.591-600
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    • 2018
  • The objective of this study was to determine the changes in phytoplankton and long-term water quality of Juksan-Weir in Yeongsan River that took place between April 2010 and December 2015. The number of species used in this study was 288, which consisted of 6% of Cyanophyta, 26% of Bacillariophyta, 53% of Chlorophyta and the others (15%). The standing crops of phytoplankton ranged from $500cells{\cdot}mL^{-1}-29,950cells{\cdot}mL^{-1}$ with an average of $7,885cells{\cdot}mL^{-1}$. At the two site, 20 dominant genera of found. The dominant genera were 6 of Bacillariophyta, 6 of Cyanophyta, 7 of Chlorophyta and 1 of Cryptophyta. The most dominant genus among the phytoplankton was Stephanodiscus sp. (Total 59%, each 54% and 63%). The most dominant genus among the Cyanophyta was Microcystis sp., which had a cell abundance ratio of 17%. The results of two sites were 21% and 13%, and the upstream was higher than the downstream.

Distributional Characteristics, Population Structures and Fruition Dynamics of Korean Endemic plant, Prunus choreiana H. T. Im (한국특산 복사앵도나무(Prunus choreiana H. T. Im)의 분포특성, 개체군구조 및 결실동태)

  • Kim, Young-Chul;Chae, Hyun-Hee;Son, Sung-Won
    • Korean Journal of Environment and Ecology
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    • v.36 no.2
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    • pp.177-201
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    • 2022
  • Following the adoption of the global plant conservation strategies at the Conference of the Parties for Biodiversity Conservation, diligent actions to achieve each targets are actively carried out. In particular, the need for ecological conservation research to achieve targets 2 and 7 of GSPC-2020 has increased. The priority taxa to accomplish the objectives of GSPC-2020 are rare and endemic plants. In particular, endemic plants with limited distribution in specific regions are evaluated to face a high risk of extinction. To address the necessity to preserve endemic plants, we investigated the distribution of Prunus choreiana H. T. Im, a Korean endemic plant. After that, we examined the vegetational environment of the habitat of P. choreiana and evaluated its population structure. The productivity of its fruits and the effects of pollinators on fruit production were evaluated as well. The fruiting ratio was calculated based on the number of flowers produced. Lastly, we observed the annual growth characteristics of P. choreiana. The habitats of P. choreiana did not show a specific type of vegetation. All of them were located in a limestone area of Gangwon-do in the central Korean Peninsula and occupied a site where the coverage of the tree layer and the sub-tree layer was not high or did not exist. The population structure of P. choreiana contained a high proportion of mature plants capable of producing fruits and a low proportion of seedlings and Juvenile plants. We found that the production of fruits required pollinators and was affected by the performance of each plant. Although P. choreiana produces many flowers, only a maximum of 20% and only 2-6% on average bear fruits. These flowering characteristics may be due to pollinators' low abundance and activity during the flowering season (between mid-March and early April), suggesting that many flowers are needed to attract more pollinators. We rarely observed the re-establishment of seedlings in the population of P. choreiana. Despite that, we predict the population to persist owing to its long lifespan and periodic production of numerous fruits. However, if the tree layer and sub-tree layer in competing status with P. choreiana increase their crown density, they are expected to inhibit the growth of P. choreiana and affect the risk of its extinction. Therefore, the current changes in the vegetational environment of the habitats are expected to decrease the number and extent of P. choreiana in the long term. The results of this study may serve as primary and important data necessary for the achievement of GSPC-2020 objectives.