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Mechanosensitive ion channels in apoptosis and ferroptosis: focusing on the role of Piezo1

  • Yong-Jae Kim;Jeongeun Hyun
    • BMB Reports
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    • v.56 no.3
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    • pp.145-152
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    • 2023
  • Mechanosensitive ion channels sense mechanical stimuli applied directly to the cellular membranes or indirectly through their tethered components, provoking cellular mechanoresponses. Among others, Piezo1 mechanosensitive ion channel is a relatively novel Ca2+-permeable channel that is primarily present in non-sensory tissues. Recent studies have demonstrated that Piezo1 plays an important role in Ca2+-dependent cell death, including apoptosis and ferroptosis, in the presence of mechanical stimuli. It has also been proven that cancer cells are sensitive to mechanical stresses due to higher expression levels of Piezo1 compared to normal cells. In this review, we discuss Piezo1-mediated cell death mechanisms and therapeutic strategies to inhibit or induce cell death by modulating the activity of Piezo1 with pharmacological drugs or mechanical perturbations induced by stretch and ultrasound.

The Influence of Several Drugs Affecting $Ca^{2+}$ Influx on Frequency-tension Curve of Rat Left Atrium (쥐의 좌심방에서 세포막을 통한 $Ca^{2+}\;Flux$에 영향을 주는 약물이 자극빈도-장력 곡선에 미치는 영향)

  • Kim, Chan-Yun;Ahn, Sok-Kyun;Suh, Chang-Kook;Kang, Doo-Hee
    • The Korean Journal of Physiology
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    • v.23 no.2
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    • pp.329-337
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    • 1989
  • Cardiac muscles show stimulation frequency-dependent tension changes i.e. Bowditch phenomenon and Woodworth phenomenon, the former is an increase of tension with the increase of stimulation frequency, whereas the latter is an increase of tension with a decrease of stimulation frequency. Bowditch phenomenon is seen in the range of frequency 1.0 cps and above, and Woodworth phenomenon below the frequency 1.0 cps in the most of mammalian cardiac atrium. To throw some light on the possible mechanism of both phenomena in rat atrium, influences of drugs affecting $Ca^{2+}$ influx through the plasma membrane $(verapamil,\;La^{3+},\;norepinephrine)$ and $Ca^{2+}$ release from sarcoplasmic reticulum (SR) on frequency-tension curve were studied. The results obtained are summarized as follows: 1) At low temperature $(27.5^{\circ}C)$, both Bowditch and Woodworth phenomenon were demonstrated. But Bowditch phenomenon disappeared at the temperature above $(32.5^{\circ}C)$. 2) At $(27.5^{\circ}C)$, in the presence of verapamil, a $Ca^{2+}$ channel blocker, a time course of change in the frequency-tension was studied. It was found that Bowditch phenomenon was affected before the Woodworth phenomenon, then the former was completely disappeared. At $(32.5^{\circ}C)$, where no Bow-ditch is seen in normal atrial muscle, Bowditch phenomenon was reappeared by an administration of norepinephrine suggesting again that slow inward current of such as $Ca^{2+}$ channel is closely related to Bowditch phenomenon. 3) At $27.5^{\circ}C$, in the presence of $La^{3+}$, although tensions were decreased at all stimulation frequencies, Bowditch and Woodworth phenomenon were still demonstrated. However in the presence of both $La^{3+}$ and verapamil, Bowditch phenomena was disappeared suggesting that $La^{3+}$ is less effective in blocking $Ca^{2+}$ channel than verapamil. 4) At $27.5^{\circ}C$, in the presence of ryanodine, an inhibitor of calcium release from SR, Woodworth phenomenon was disappeared, which was consistent with previous reports of others, suggesting that $Ca^{2+}$ release from SR is closely related to Woodworth phenomenon. From the above findings, it may be concluded that Bowditch phenomenon is dependent on the magnitude of $Ca^{2+}$ influx through slow channel and Woodworth phenomenon is dependent on the amount of $Ca^{2+}$ stored in SR.

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Apoptosis Event of Pre-implantation Development Stages in Porcine IVF Embryos (착상 전 돼지 체외수정 배아 발달 단계에서의 세포 자멸사 현상)

  • Hong, Seong-Min;Jeon, Yu-Byeol;Hyun, Sang-Hwan
    • Journal of Embryo Transfer
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    • v.24 no.3
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    • pp.183-187
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    • 2009
  • In this study, we aimed to determine whether the evaluated markers of cell death could be found at particular developmental stages of normal porcine in vitro fertilization (IVF) embryos. We investigated the characteristics of spontaneous and induced apoptosis during preimplantation development stages of porcine IVF embryos. In experiment 1, to induce apoptosis of porcine IVF embryos, porcine IVF embryos at 22h post insemination were treated at different concentration of actinomycin D (0, 5, 50 and 500 ng/ml in NCSU medium). Treated embryos were incubated at $39^{\circ}C$ in 5% $CO_2$, 5% $O_2$ for 8h, and then washed to NCSU medium and incubated until blastocyst (BL) stage. We examined cleavage rate at 2days and BL development rate at 7days after in vitro culture. A significantly lower rate of cleavage was found in the 500 ng/ml group compared to others (500 ng/ml vs. 0, 5, 50 ng/ml; 27.8 % vs. 50.0%, 41.2%, 35.9%), and BL formation rate in 500 ng/ml was lower than that of others (500 ng/ml vs. 0, 5, 50 ng/ml; 8.0% vs. 12.6%, 11.2%, 12.6%). In experiment 2, to evaluate apoptotic cells, we conducted TUNEL assay based on morphological assessment of nuclei and on detection of specific DNA degradation under fluorescence microscope. This result showed that apoptosis is a normal event during preimplantation development in control group (0 ng/ml actinomycin D). A high number of BL derived control group contained at least one apoptotic cell. Actinomycin D treated BLs responded to the presence of apoptotic inductor by significant decrease in the average number of blastomeres and increase in the incidence of apoptotic cell death. In 500 ng/ml group, the incidence of apoptosis increased at 4-cell stage and later. This result suggested that apoptosis is a process of normal embryonic development and actinomycin D is useful tool for the apoptosis study of porcine preimplantation embryos.

Differential Morphological, Structural and Biological Characteristics of Cysts in Heterodera Species in Korea

  • Han, Ga Ram;Kang, Heonil;Choi, In Soo;Kim, Donggeun;Yun, Hye Young;Kim, Young Ho
    • The Plant Pathology Journal
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    • v.36 no.6
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    • pp.628-636
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    • 2020
  • Morphological (cyst shape, color, and sizes [length (L), maximum width (W), volume and "a" (L/W)]), structural (vulvar cone slope angle [VCSA], surface wrinkle [VCSW], cyst wall thickness, composition, and texture) and biological characteristics (fecundity, hatching, and emergence [number of second-stage juveniles (J2) from a cyst]) in preceding Heterodera glycines (Hg), currently-recorded H. sojae (Hs) and H. trifolii (Ht) were examined by microscopy. Cysts were lemon-shaped, indicating the genus is Heterodera except for Hs that formed frequently globular cysts with significantly flatter VCSA (102.2°) with smooth VCSW than Hg (50.6°) and Ht (82.0°), but not genus Globodera because of the presence of vulvar cone in Hs. Ht was significantly larger in all morphological characteristics than Hg and Hs, suggesting Ht may be diagnosed differentially by cyst sizes and also host plant preferences. Hs showed smaller "a" value with more globular shape and stronger structures with more thickened and strengthened collagen-like texture of cyst wall than Hg and Ht. This suggests Hs may be diagnosed differently by structural characteristics from the others, especially Hg with similar cyst sizes. There were no significant differences in emergence (inoculum potential) among cyst nematodes due to the offset of fecundity and hatching rate; however, the inoculum potential of Hs may be not so persistent as Hg and Ht in fields because of its lower fecundity and higher hatching rate (causing rapid inoculum loss) than the others. These characteristics of cysts provide information useful for simple and differential diagnoses and reliable management of cyst nematodes.

Attitude toward One's Own Aging among Korean Middle-aged Adults and the Elderly (중장년 성인과 노인의 노화에 대한 태도)

  • Jo, Ahra;Oh, Heeyoung
    • Korean Journal of Adult Nursing
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    • v.29 no.1
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    • pp.41-50
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    • 2017
  • Purpose: The purpose of this study was to identify and compare the factors influencing attitude toward one's own aging among Korean middle-aged adults and the elderly. Methods: A cross sectional study was performed with a total sample of 70 middle-aged adults and 64 elderly reside in two metropolitan areas. Data were collected from August 2015 to November 2015 using the Perceived Health Status Scale, the Health Locus of Control Scale and the Attitude Toward own Aging (ATOA) Scale. The statistics used include percentage, t-test, Pearson's correlation coefficient, and multiple regression. Results: Mean age for each age group were about 52 and 76 years old for middle-aged adults and the elderly respectively. A considerable proportion of all participants reported a negative attitude toward aging. Perceived health status was the common factor influencing attitude toward one's own aging in both age groups. Middle-aged adults identified presence of chronic illness and internal health locus of control as important factors. In contrast, the elderly reported that education and others-dependent health locus of control such as powerful others had a significant impact on ATOA. Each regression model explained 31% and 55% of the total variance of ATOA among middle-aged adults and among the elderly. Conclusion: Both middle-aged adults and the elderly with low perceived health status are at risk of negative ATOA's. The type health locus of control need to be identified and utilized based on individuals' tendency to improve positive ATOA. That is, middle-aged adults might need reinforcement of their self-will whereas the elderly might need enhancement of social support and network of family and healthcare providers.

The Applications of Online, Multi-User Virtual Environments for Architectural & Interior Design Communication (건축·인테리어 디자인과정의 커뮤니케이션을 위한 온라인 다중 사용자 가상환경 활용 사례 연구)

  • Hong, Seung-Wan;Yoo, Chang-Geun
    • Journal of the Korean housing association
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    • v.25 no.1
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    • pp.41-50
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    • 2014
  • Architectural & Interior design communication is a process of exchanging information between architects and other professionals, clients, and prospectus users, and a design medium is a means of communication. Using non-immersive, conventional media, it is challenging for architects communicate physical details and users' activities in not yet built three-dimensional buildings to others. Recent advances online, Multi-User Virtual Environments (MUVEs) allow architects and other professionals to experience a virtually constructed building together using anthropomorphic avatars. In addition, MUVEs also enable them to be aware of the presence and activity of each other. Previous studies suggest that the aforementioned characteristics of MUVEs may facilitate communication between architects and others. But these are focused on communication in controlled experimental conditions. This paper discusses the ways in which MUVEs are applied for authentic and long-term collaboration, design studio, and cultural heritage reconstruction projects, produced by digital design group at the UC Berkeley and the Technion-Israel Institute of Technology, and analyzes the influences of MUVEs on those projects. MUVEs helped more precise communication between architects, electronic engineers, and medical staffs, who are collaborating for developing pioneering technology for hospitals. In design studios, MUVEs allowed students to experience other students' design outputs, and thus helped them share ideas mutually. In addition, in cultural heritage reconstruction projects, MUVEs were used for communicating with historians and residents in order to collect evidence. Based on this study, we propose that MUVEs have strong potential for enhancing the communication between architects and other professionals.

A Study on the Adsorption Characteristics of Phenol in the presence of Humic Acid Using Activated Carbon Fiber (섬유상활성탄소를 이용한 Humic Acid 공존시 페놀의 흡착특성에 관한 연구)

  • Tak, Seong-Jae;Seo, Seong-Wen;Kim, Seong-Sun;Kim, Jin-Man
    • Journal of Korean Society of Water and Wastewater
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    • v.14 no.1
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    • pp.54-61
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    • 2000
  • Recently, our circumstances are threatened by an accident that leakage of under ground storage tank and illegal dumping of synthetic organic compounds at chemical plants and many treatment methods, Activated carbon adsorption, Ozonization, Membrane filtration and Photocatalystic oxidation, are developed to remove such a synthetic organic compounds. And it has reported that Activated carbon adsorption have a great removal efficiency to nondegradable matters and organic compounds which have a high molecular weight. Comparing with other adsorbents, Activated carbon adsorption have a worse efficiency when ad desorption speed is low. Thus improved type of adsorbents was invented and one of those is Activated Carbon Filter. The purpose of this study was getting information about adsorption characteristic phenol which can be applied Activated Carbon Fiber and Granular Activated Carbon. In detail, With comparing removal characteristics of phenol in the presence Humic Acid using Activated Carbon Fiber(ACF) and Granular Activated. Carbon(GAC), it is to certify an effective application of Activated Carbon Fiber. At the range of this study, Batch test, Isotherm adsorption test and Factorial analysis, following conclusion were obtained from the results of this study. Batch test was carried to know time of adsorption equilibrium. In this study about time of adsorption equilibrium by ACF was faster than GAC's, for developed micropore of ACF. From the result of phenol adsorption test, High removal rate of adsorption is shown at pH 5. The result of lsotherm adsorption test, it has represented that the Freundlich's isotherm is most suitable one in others, that a ACF's adsorption capacity is more excellent than GAC's. Adsorption of phenol exiting humic acid is decreased getting raised humic acid concentration. Since ACF's micropore is developed at this time, an effect of high molecular humic acid is lower. Factorial analysis was carried to know about Main effect which was injection dosage of adsorbent in the range of this study.

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Forward Gene Mutation Assay of Seven Benzophenone-type UV Filters using L5178Y Mouse Lymphoma Cell

  • Jeon, Hee-Kyung;Sarma, Sailendra Nath;Kim, Youn-Jung;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.3 no.1
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    • pp.23-30
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    • 2007
  • The effects of high energy short wave solar radiation on human skin have received much publicity as the major cause of accelerated skin ageing and of skin cancers. To meet public demand, the cosmetic industry has developed sun protection factor products, which contain a variety of so-called "UV filters", among others benzophenone (BP) and its metabolites are the widely used UV filters. UV filters are also used to prevent UV light from damaging scents and colors in a variety of cosmetics products and to protect of plastic products against light-induced degradation. There are many variants of BP in use. In this respect, to regulate and to evaluate the hazardous effect of BP-type UV filters will be important to environment and human health. The genotoxicity of 7 BP-type UV filters was evaluated in L5178Y $(tk^{+/-})$ mouse lymphoma cells in vitro. BP, benzhydrol, 4-hydroxybenzophenone 2-hydroxy-4-methoxybenzophenone and 2, 4-dihydroxybenzophenone did not induce significant mutation frequencies both in the presence and absence of metabolic activation system. 2, 2'-Dihydroxy-4-methoxybenzophenone appeared the positive results at the highest dose, i.e. 120.4 ${\mu}g/mL$ only in the absence of metabolic activation system. And also, 2, 3, 4-trihydroxybenzophenone revealed a significant increase of mutation frequencies in the range of 138.1-207.2 ${\mu}g/mL$ in the absence of metabolic activation system and 118.3-354.8 ${\mu}g/mL$ in the presence of metabolic activation system. Through the results of MLA with 7 BP-type UV filters in L5178Y cells in vitro, we may provide the important clues on the genotoxic potentials of these BP-type UV filters.

Function of heat shock protein and Immune response (Heat shock protein의 기능과 면역 반응)

  • 김세진
    • The Microorganisms and Industry
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    • v.25 no.1
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    • pp.2-9
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    • 1999
  • A study was made on enzymes of carbohydrate metabolism in T. concretivorus grown with and without glucose. The present results show that T. concretivorus possesses high activities of pentose shunt pathway and related enzymes, glucokinase, G-6-P dehydrogenase, 6-PG dehydrogenase, and phosphoglucoisomerase, but low activities of enzymes unique to EMP(fructose-1,6-diphosphate aldolase). Although the synthesis of the latter enzymes remains largely unaffected by the growth enviroment, that of the former is stimulated by glucose. And the failure to detect ED pathway enzymes in cells grown in thiosulate or thiosulfate-glucose medium eliminates the ED pathway as a significant route of glucose catabolism in T.concretivorus. These results suggest that pentose shunt pathway performs an energetic role in glucose metabolism by T.concretivorus with EMP as a subway. The absence of ED pathway and the presence of pentose shunt pathway which is the major route of catabolism in T.concretivorus are similar to those of other obligately chemolitho-trophic thiobacilli. The G-6-P and 6-PG dehydrogenase are both NAD and NADP specific, but MAD predominant. However, the 3-PGAL dehydrogenase is only NAD specific. Since the specific activity of 3-PGAL generated from glucose is converted mainly into pyruvate which is channeled into the TCA cycle. All enzymes of the TCA cycle tested and NADH oxidase are detected in the cells of T.concretivorus grown in thiosulfate. The specific activities of fumarase and isocitrate dehydrogenase are high and others are low. The presence of two isocitrate dehydrogenase (NAD-and NADP-linked) may have important regulatory function for this organism. The activity of NAD-oxidase, which is implicated in the energy generating metabolism, was very high in the crude cell-free extract of T.concretivorus, recording 55.11 m.mu. mole/min/mg protein. This well coincides with the fact that activities of NAD-linked G-6-P dehydrogenase, 6-PG dehydrogenase and 3-PGAL dehydrogenase were high.

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The enzymatic Studies on Metabolic Pathways in Thiobacillus conctetivorus (Thiobacillus concretivorus의 대사경로에 관한 효소학적 연구)

  • 하영칠
    • Korean Journal of Microbiology
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    • v.11 no.1
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    • pp.1-18
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    • 1973
  • A study was made on enzymes of carbohydrate metabolism in T. concretivorus grown with and without glucose. The present results show that T. concretivorus possesses high activities of pentose shunt pathway and related enzymes, glucokinase, G-6-P dehydrogenase, 6-PG dehydrogenase, and phosphoglucoisomerase, but low activities of enzymes unique to EMP(fructose-1, 6-diphosphate aldolase). Although the synthesis of the latter enzymes remains largely unaffected by the growth enviroment, that of the former is stimulated by glucose. And the failure to detect ED pathway enzymes in cells grown in thiosulate or thiosulfate-glucose medium eliminates the ED pathway as a significant route of glucose catabolism in T.concretivorus. These results suggest that pentose shunt pathway performs an energetic role in glucose metabolism by T.concretivorus with EMP as a subway. The absence of ED pathway and the presence of pentose shunt pathway which is the major route of catabolism in T.concretivorus are similar to those of other obligately chemolitho-trophic thiobacilli. The G-6-P and 6-PG dehydrogenase are both NAD and NADP specific, but MAD predominant. However, the 3-PGAL dehydrogenase is only NAD specific. Since the specific activity of 3-PGAL generated from glucose is converted mainly into pyruvate which is channeled into the TCA cycle. All enzymes of the TCA cycle tested and NADH oxidase are detected in the cells of T.concretivorus grown in thiosulfate. The specific activities of fumarase and isocitrate dehydrogenase are high and others are low. The presence of two isocitrate dehydrogenase (NAD-and NADP-linked) may have important regulatory function for this organism. The activity of NAD-oxidase, which is implicated in the energy generating metabolism, was very high in the crude cell-free extract of T.concretivorus, recording 55.11 m$\mu$ mole/min/mg protein. This well coincides with the fact that activities of NAD-linked G-6-P dehydrogenase, 6-PG dehydrogenase and 3-PGAL dehydrogenase were high.

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