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Manganese and Iron Interaction: a Mechanism of Manganese-Induced Parkinsonism

  • Zheng, Wei
    • Proceedings of the Korea Environmental Mutagen Society Conference
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    • 2003.10a
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    • pp.34-63
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    • 2003
  • Occupational and environmental exposure to manganese continue to represent a realistic public health problem in both developed and developing countries. Increased utility of MMT as a replacement for lead in gasoline creates a new source of environmental exposure to manganese. It is, therefore, imperative that further attention be directed at molecular neurotoxicology of manganese. A Need for a more complete understanding of manganese functions both in health and disease, and for a better defined role of manganese in iron metabolism is well substantiated. The in-depth studies in this area should provide novel information on the potential public health risk associated with manganese exposure. It will also explore novel mechanism(s) of manganese-induced neurotoxicity from the angle of Mn-Fe interaction at both systemic and cellular levels. More importantly, the result of these studies will offer clues to the etiology of IPD and its associated abnormal iron and energy metabolism. To achieve these goals, however, a number of outstanding questions remain to be resolved. First, one must understand what species of manganese in the biological matrices plays critical role in the induction of neurotoxicity, Mn(II) or Mn(III)? In our own studies with aconitase, Cpx-I, and Cpx-II, manganese was added to the buffers as the divalent salt, i.e., $MnCl_2$. While it is quite reasonable to suggest that the effect on aconitase and/or Cpx-I activites was associated with the divalent species of manganese, the experimental design does not preclude the possibility that a manganese species of higher oxidation state, such as Mn(III), is required for the induction of these effects. The ionic radius of Mn(III) is 65 ppm, which is similar to the ionic size to Fe(III) (65 ppm at the high spin state) in aconitase (Nieboer and Fletcher, 1996; Sneed et al., 1953). Thus it is plausible that the higher oxidation state of manganese optimally fits into the geometric space of aconitase, serving as the active species in this enzymatic reaction. In the current literature, most of the studies on manganese toxicity have used Mn(II) as $MnCl_2$ rather than Mn(III). The obvious advantage of Mn(II) is its good water solubility, which allows effortless preparation in either in vivo or in vitro investigation, whereas almost all of the Mn(III) salt products on the comparison between two valent manganese species nearly infeasible. Thus a more intimate collaboration with physiochemists to develop a better way to study Mn(III) species in biological matrices is pressingly needed. Second, In spite of the special affinity of manganese for mitochondria and its similar chemical properties to iron, there is a sound reason to postulate that manganese may act as an iron surrogate in certain iron-requiring enzymes. It is, therefore, imperative to design the physiochemical studies to determine whether manganese can indeed exchange with iron in proteins, and to understand how manganese interacts with tertiary structure of proteins. The studies on binding properties (such as affinity constant, dissociation parameter, etc.) of manganese and iron to key enzymes associated with iron and energy regulation would add additional information to our knowledge of Mn-Fe neurotoxicity. Third, manganese exposure, either in vivo or in vitro, promotes cellular overload of iron. It is still unclear, however, how exactly manganese interacts with cellular iron regulatory processes and what is the mechanism underlying this cellular iron overload. As discussed above, the binding of IRP-I to TfR mRNA leads to the expression of TfR, thereby increasing cellular iron uptake. The sequence encoding TfR mRNA, in particular IRE fragments, has been well-documented in literature. It is therefore possible to use molecular technique to elaborate whether manganese cytotoxicity influences the mRNA expression of iron regulatory proteins and how manganese exposure alters the binding activity of IPRs to TfR mRNA. Finally, the current manganese investigation has largely focused on the issues ranging from disposition/toxicity study to the characterization of clinical symptoms. Much less has been done regarding the risk assessment of environmenta/occupational exposure. One of the unsolved, pressing puzzles is the lack of reliable biomarker(s) for manganese-induced neurologic lesions in long-term, low-level exposure situation. Lack of such a diagnostic means renders it impossible to assess the human health risk and long-term social impact associated with potentially elevated manganese in environment. The biochemical interaction between manganese and iron, particularly the ensuing subtle changes of certain relevant proteins, provides the opportunity to identify and develop such a specific biomarker for manganese-induced neuronal damage. By learning the molecular mechanism of cytotoxicity, one will be able to find a better way for prediction and treatment of manganese-initiated neurodegenerative diseases.

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Detection Characteristics of Gamma-Irradiated Korean Medicinal Herbs by Using PSL, TL, and ESR (PSL, TL 및 ESR 분석에 의한 감마선 조사 한약재의 검지 특성)

  • Yang, Hee-Sun;Park, Yong-Dae;Jin, Chang-Hyun;Choi, Dae-Seong;Chung, Hyung-Wook;Byun, Myung-Woo;Jeong, Il-Yun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.11
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    • pp.1529-1533
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    • 2008
  • The detection characteristics of gamma-irradiated ($0{\sim}10.0\;kGy$) medicinal herbs (Platycodon grandiflorum, Acanthopanax chiisanensis) were investigated by photostimulated luminescence (PSL), thermoluminescence (TL), and electron spin resonance (ESR). The results of the PSL, a first screening method in comparison with the TL, showed photon counts greater than 5,000 counts/60 s (positive) in the irradiated samples, while the non-irradiated samples yielded photon counts less than 700 counts/60 s (negative). The TL was also applied for the detection method of irradiated medicinal herbs and showed that the non-irradiated sample revealed a glow curve with a low intensity, while the irradiated samples showed a higher intensity. These results were normalized by re-irradiating the mineral grains with a irradiation dose of 1.0 kGy, and a second glow curve was recorded. The ratio of the intensity of the first glow curve ($TL_1$) to that after the normalization dose ($TL_2$) was determined and compared with the recommended threshold values. TL ratio ($TL_1/TL_2$) was below 0.007 for the non-irradiated sample and higher than 0.1 for all irradiated samples (above 1.0 kGy). ESR spectroscopy revealed specific signals (6.065 mT) derived from free radicals in cellulose containing irradiated medicinal herbs. The P. grandiflorum showed clearer signals than A. chiisanensis. From the results of our studies, the PSL, TL, and ESR determinations were found to be suitable for the detection of irradiated medicinal herbs such as P. grandiflorum and A. chiisanensis.

An Exploratory Study on the Success Factors of Silicon Valley Platform Business Ecosystem: Focusing on IPA Analysis and Qualitative Analysis (실리콘밸리 플랫폼 기업생태계의 성공요인에 관한 탐색적 연구: IPA 분석과 질적 분석을 중심으로)

  • Yeonsung, Jung;Seong Ho, Lee
    • Asia-Pacific Journal of Business Venturing and Entrepreneurship
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    • v.18 no.1
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    • pp.203-223
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    • 2023
  • Recently, the platform industry is rapidly growing in the global market, and competition is intensifying at the same time. Therefore, in order for domestic platform companies to have global competitiveness in the platform market, it is necessary to study the platform business ecosystem and success factors. However, most of the recent platform-related studies have been theoretical studies on the characteristics of platform business status analysis, platform economy, and indirect network externalities of platforms. Therefore, this study comprehensively analyzed the success factors of Silicon Valley's business ecosystem proposed in previous studies, and at the same time analyzed the success factors extracted from stakeholders in the actual Silicon Valley platform business ecosystem. And based on these factors, an IPA analysis was conducted as a way to propose a success plan to stakeholders in the platform business ecosystem. As a result of the analysis, among the success factors collected through previous studies, manpower, capital, and challenge culture were identified as factors that are relatively well maintained in both importance and satisfaction in Silicon Valley. In the end, it can be seen that the creation of an environment and culture in which Silicon Valley can use it to challenge itself based on excellent human resources and abundant capital contributes the most to the success of Silicon Valley's platform business. On the other hand, although it is of high importance to Silicon Valley's platform corporate ecosystem, the factors that show relatively low satisfaction among stakeholders are 'learning and benchmarking among active companies' and 'strong ties and cooperation between members', and it is analyzed that interest and effort are needed to strengthen these factors in the future. Finally, the systems and policies necessary for market autonomous competition, 'business support service industry', 'name value', and 'spin-off start-up' were important factors in literature research, but the importance and satisfaction of these factors were lowered due to changes in the times and environment. This study has academic implications in that it comprehensively analyzes the success factors of Silicon Valley's business ecosystem proposed in previous studies, and at the same time analyzes the success factors extracted from stakeholders in the actual Silicon Valley platform business ecosystem. In addition, there is another academic implications that importance and satisfaction were simultaneously examined through IPA analysis based on these various extracted factors. As for academic implications, it is meaningful in that it contributed to the formation of the domestic platform ecosystem by providing the government and companies with concrete information on the success factors of the platform business ecosystem and the theoretical grounds for the growth of domestic platform businesses.

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