• Title/Summary/Keyword: biological macromolecules

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Major ginsenosides from Panax ginseng promote aerobic cellular respiration and SIRT1-mediated mitochondrial biosynthesis in cardiomyocytes and neurons

  • Huang, Qingxia;Lou, Tingting;Lu, Jing;Wang, Manying;Chen, Xuenan;Xue, Linyuan;Tang, Xiaolei;Qi, Wenxiu;Zhang, Zepeng;Su, Hang;Jin, Wenqi;Jing, Chenxu;Zhao, Daqing;Sun, Liwei;Li, Xiangyan
    • Journal of Ginseng Research
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    • v.46 no.6
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    • pp.759-770
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    • 2022
  • Background: Aerobic cellular respiration provides chemical energy, adenosine triphosphate (ATP), to maintain multiple cellular functions. Sirtuin 1 (SIRT1) can deacetylate peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) to promote mitochondrial biosynthesis. Targeting energy metabolism is a potential strategy for the prevention and treatment of various diseases, such as cardiac and neurological disorders. Ginsenosides, one of the major bioactive constituents of Panax ginseng, have been extensively used due to their diverse beneficial effects on healthy subjects and patients with different diseases. However, the underlying molecular mechanisms of total ginsenosides (GS) on energy metabolism remain unclear. Methods: In this study, oxygen consumption rate, ATP production, mitochondrial biosynthesis, glucose metabolism, and SIRT1-PGC-1α pathways in untreated and GS-treated different cells, fly, and mouse models were investigated. Results: GS pretreatment enhanced mitochondrial respiration capacity and ATP production in aerobic respiration-dominated cardiomyocytes and neurons, and promoted tricarboxylic acid metabolism in cardiomyocytes. Moreover, GS clearly enhanced NAD+-dependent SIRT1 activation to increase mitochondrial biosynthesis in cardiomyocytes and neurons, which was completely abrogated by nicotinamide. Importantly, ginsenoside monomers, such as Rg1, Re, Rf, Rb1, Rc, Rh1, Rb2, and Rb3, were found to activate SIRT1 and promote energy metabolism. Conclusion: This study may provide new insights into the extensive application of ginseng for cardiac and neurological protection in healthy subjects and patients.

Clinical Appliance of Structure-Function Studies of Salivary Macromolecules (타액 단백질의 기능 및 구조 연구의 임상적 적용)

  • 고홍섭
    • Journal of Oral Medicine and Pain
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    • v.23 no.3
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    • pp.241-247
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    • 1998
  • Salivary research is at a critical crossroads regarding the clinical application of the basic knowledge. The purpose of this article is to introduce the current progress on salivary research to Korean dental scientists. The accumulated results based on advance technologies such as protein chemistry, molecular biology, and structural biology have showed that salivary macromolecules need structural requirements for proper function. Currently, several concepts or principles, which can be applied to salivary macromolecules, have been suggested. These include the role of molecules' conformation on biological activity, their multifunctional nature, their redundancy of function, their amphifunctional properties, and the potential importance of complexing between molecules. These concepts and the information available will help the development of saliva substitutes, the design of drug carriers and chimera molecules with enhanced function and the development of gene therapy protocols. These approaches will alleviate or restore lost salivary function and can be used to treat various kinds of oral and systemic diseases.

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Ginsenoside compound K protects against cerebral ischemia/ reperfusion injury via Mul1/Mfn2-mediated mitochondrial dynamics and bioenergy

  • Qingxia Huang;Jing Li;Jinjin Chen;Zepeng Zhang;Peng Xu;Hongyu Qi;Zhaoqiang Chen;Jiaqi Liu;Jing Lu;Mengqi Shi;Yibin Zhang;Ying Ma;Daqing Zhao;Xiangyan Li
    • Journal of Ginseng Research
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    • v.47 no.3
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    • pp.408-419
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    • 2023
  • Background: Ginsenoside compound K (CK), the main active metabolite in Panax ginseng, has shown good safety and bioavailability in clinical trials and exerts neuroprotective effects in cerebral ischemic stroke. However, its potential role in the prevention of cerebral ischemia/reperfusion (I/R) injury remains unclear. Our study aimed to investigate the molecular mechanism of ginsenoside CK against cerebral I/R injury. Methods: We used a combination of in vitro and in vivo models, including oxygen and glucose deprivation/reperfusion induced PC12 cell model and middle cerebral artery occlusion/reperfusion induced rat model, to mimic I/R injury. Intracellular oxygen consumption and extracellular acidification rate were analyzed by Seahorse multifunctional energy metabolism system; ATP production was detected by luciferase method. The number and size of mitochondria were analyzed by transmission electron microscopy and MitoTracker probe combined with confocal laser microscopy. The potential mechanisms of ginsenoside CK on mitochondrial dynamics and bioenergy were evaluated by RNA interference, pharmacological antagonism combined with co-immunoprecipitation analysis and phenotypic analysis. Results: Ginsenoside CK pretreatment could attenuate mitochondrial translocation of DRP1, mitophagy, mitochondrial apoptosis, and neuronal bioenergy imbalance against cerebral I/R injury in both in vitro and in vivo models. Our data also confirmed that ginsenoside CK administration could reduce the binding affinity of Mul1 and Mfn2 to inhibit the ubiquitination and degradation of Mfn2, thereby elevating the protein level of Mfn2 in cerebral I/R injury. Conclusion: These data provide evidence that ginsenoside CK may be a promising therapeutic agent against cerebral I/R injury via Mul1/Mfn2 mediated mitochondrial dynamics and bioenergy.

Decomposition of Biological Macromolecules by Plasma Generated with Helium and Oxygen

  • Kim Seong-Mi;Kim Jong-Il
    • Journal of Microbiology
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    • v.44 no.4
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    • pp.466-471
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    • 2006
  • In this study, we attempted to characterize the biomolecular effects of an atmospheric-pressure cold plasma (APCP) system which utilizes helium/oxygen $(He/O_2)$. APCP using $He/O_2$ generates a low level of UV while generating reactive oxygen radicals which probably serve as the primary factor in sterilization; these reactive oxygen radicals have the advantage of being capable to access the interiors of the structures of microbial cells. The damaging effects of plasma exposure on polypeptides, DNA, and enzyme proteins in the cell were assessed using biochemical methods.

Using Harmonic Analysis and Optimization to Study Macromolecular Dynamics

  • Kim Moon-K.;Jang Yun-Ho;Jeong Jay-I.
    • International Journal of Control, Automation, and Systems
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    • v.4 no.3
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    • pp.382-393
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    • 2006
  • Mechanical system dynamics plays an important role in the area of computational structural biology. Elastic network models (ENMs) for macromolecules (e.g., polymers, proteins, and nucleic acids such as DNA and RNA) have been developed to understand the relationship between their structure and biological function. For example. a protein, which is basically a folded polypeptide chain, can be simply modeled as a mass-spring system from the mechanical viewpoint. Since the conformational flexibility of a protein is dominantly subject to its chemical bond interactions (e.g., covalent bonds, salt bridges, and hydrogen bonds), these constraints can be modeled as linear spring connections between spatially proximal representatives in a variety of coarse-grained ENMs. Coarse-graining approaches enable one to simulate harmonic and anharmonic motions of large macromolecules in a PC, while all-atom based molecular dynamics (MD) simulation has been conventionally performed with an aid of supercomputer. A harmonic analysis of a macroscopic mechanical system, called normal mode analysis, has been adopted to analyze thermal fluctuations of a microscopic biological system around its equilibrium state. Furthermore, a structure-based system optimization, called elastic network interpolation, has been developed to predict nonlinear transition (or folding) pathways between two different functional states of a same macromolecule. The good agreement of simulation and experiment allows the employment of coarse-grained ENMs as a versatile tool for the study of macromolecular dynamics.

BIOLOGICAL HUMAN MONITORING OF CARCINOGEN EXPOSURE: A NEW STRATEGY IN CANCER PREVENTION

  • Lee, Byung-Mu
    • Toxicological Research
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    • v.6 no.1
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    • pp.63-73
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    • 1990
  • Human exposure to environmental carcinogens can be detected by a number of methods including immunoassay, $^{32}P-postlabeling$ assay, and fluorescence technique. These assays have been applied to measure biological markers of carcinogen-adducts formed with macromolecules such as DNA, RNA and protein. In an attempt to investigate causal relationships between carcinogen exposure and tumor formation, specific carcinogen-adducts have been quantitated from human tissues and body fluids of cancer patients, occupational workers heavily exposed to certain carcinogens, smokers and controls. Carcinogens studied for biological human monitoring include benzo(a)pyrene, aflatoxin B1, UV light, ethylene oxide, 8-methoxypsoralen, 4-aminobiphenyl, vinyl choride, N-nitrosamine, cisplatin and other chemotherapeutic agents. Relevance of human monitoring for cancer research, progress in this field, methods to detect carcinogen-adducts are reviewed here. It is hoped that these approaches will be used for the risk assessment of carcinogen exposure, cancer etiology study and cancer prevention in humans.

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BIOLOGICAL HUMAN MONITORING OF CARCINOGEN EXPOSURE: A NEW STRATEGY IN CANCER PREVENTION

  • Lee, Byung-Mu
    • Toxicological Research
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    • v.6 no.1
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    • pp.61-61
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    • 1990
  • Human exposure to environmental carcinogens can be detected by a number of methods including immunoassay, $^{32}P$-postlabeling assay, and fluorescence technique. These assays have been applied to measure biological markers of carcinogen-adducts formed with macromolecules such as DNA, RNA and protein. In an attempt to investigate causal relation ships between carcinogen exposure and tumor formation, specific carcinogen-adducts have been quantitated from human tissues and body fluids of cancer patients, occupational workers heavily exposed to certain carcinogens, smokers and controls. Carcinogens studied for biological human monitoring include benzo(a)pyrene, aflatoxin B1, UV light, ethylene oxide, 8-methoxypsoralen, 4-aminobiphenyl, vinyl chloride, N-nitrosamine, cisplatin and other chemotherapeutic agents. Relevance of human monitoring for cancer research, progress in this field, methods to detect carcinogen-adducts are reviewed here. It is hoped that these approaches will be used for the risk assessment of carcinogen exposure, cancer etiology study and cancer prevention in humans.

Intercellular transport across pit-connections in the filamentous red alga Griffithsia monilis

  • Kim, Gwang Hoon;Nagasato, Chikako;Kwak, Minseok;Lee, Ji Woong;Hong, Chan Young;Klochkova, Tatyana A.;Motomura, Taizo
    • ALGAE
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    • v.37 no.1
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    • pp.75-84
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    • 2022
  • Intercellular nutrient and signal transduction are essential to sustaining multicellular organisms and maximizing the benefits of multicellularity. It has long been believed that red algal intercellular transport of macromolecules is prevented by the protein-rich pit plug within pit-connections, the only physical connection between cells. Fluorescein isothiocyanate-dextran and recombinant green fluorescence protein (rGFP) of various molecular sizes were injected into vegetative cells of Griffithsia monilis using a micromanipulator, and intercellular transport of the fluorescent probes was examined. Pit-connections were found to provide intercellular transport of tracers at rates comparable to plasmodesmata in other organisms. The time necessary for the transport to an adjacent cell was dependent on the molecular size and the direction of the transport. Fluorescent dextran of 3 kDa was transported to adjacent cells in 1-2 h after injection and migrated to all cells of the filament within 24 h, but fluorescent dextran of 10-20 kDa took 24 h to transfer to neighboring cells. The migration occurred faster towards adjacent reproductive cells and to apical cells than basally. Fluorescent tracers above 40 kDa and rGFP was not transported to neighboring cells, but accumulated near the pit plug. Our results suggest that pit-connections are conduit for macromolecules between neighboring cells and that these size-specific conduits allow intercellular communication between the vegetative cells of red algae.

Exploitation of the Dose/Time-Response Relationship for a New Measure of DNA Repari in the Single-Cell Gel Electrophoresis (Comet) Assay

  • Kim, Byung-Soo;Edler, Lutz;Park, Jin-Joo;Fournier, Dietrich Von;Haase, Wulf;Sautter-Bihl, Mare-Luise;Hagmuller, Egbert;Gotzes, Florian;Thielmann, Heinz Walter
    • Toxicological Research
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    • v.20 no.2
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    • pp.89-100
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    • 2004
  • The comet assay (also called the single-cell gel electrophoresis assay) has been widely used for detecting DNA damage and repair in individual cells. Since the conventional methods of evaluating comet assay data using frequency statistics are unsatisfactory we developed a new quantitative measure of DNA damage/repair that is based on all information residing in the dose/time-response curves of a comet experiment. Blood samples were taken from 25 breast cancer patients before undergoing radiotherapy. The comet assay was performed under alkaline conditions using isolated lymphocytes. Tail DNA, tail length, tail moment and tail inertia of the comet were measured for each patient at four doses of $\gamma$-rays (0, 2, 4 and 8 Gy) and at four time points after irradiation (0, 10, 20 and 30 min) using 100 cells each. The resulting three-dimensional dose-time response surface was modeled by multiple regression, and the second derivative, termed 2D, on dose and time was determined. A software module was programmed in SAS/AF to compute 2D values. We applied the new method successfully to data obtained from cancer patients to be assessed for their radiation sensitivity. We computed the 2D values for the four damage measures, i.e., tail moment, tail length, tail DNA and tail inertia, and examined the pairwise correlation coefficients of 2D both on the log scale and the unlogged scale. 2D values based on tail moment and tail DNA showed a high correlation and, therefore, these two damage measures can be used interchangeably as far as DNA repair is concerned. 2D values based on tail inertia have a correlation profile different from the other 2D values which may reflect different facets of DNA damage/repair. Using the dose-time response surface, other statistical models, e.g., the proportional hazards model, become applicable for data analysis. The 2D approach can be applied to all DNA repair measures, Le., tail moment, tail length, tail DNA and tail inertia, and appears to be superior to conventional evaluation methods as it integrates all data of the dose/time-response curves of a comet assay.

Development of Image-based Fluorescence Photobleaching Technique for Measuring Macromolecule Diffusion in Biological Porous Medium (생체 다공성 매질에서 분자 확산 측정을 위한 영상 기반 형광 광표백 기법 개발)

  • Lee, Dong-Hee;Lee, Jeong-Hoon;Park, Choon-Ho;Kim, Jung-Kyung
    • Journal of the Korean Society of Visualization
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    • v.7 no.1
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    • pp.9-13
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    • 2009
  • Fluorescence recovery after photobleaching (FRAP) has been widely used for the measurement of molecular diffusion in living cells and tissues. We developed an image-based FRAP (iFRAP) technique using a modified real-time microscope and a 488 nm Ar-ion laser. A fractional intensity curve was obtained from the time-lapse images of fluorescence recovery in the bleached spot to determine the diffusion coefficient of fluorescently labeled macromolecules in porous medium. We validated iFRAP through experiments with agar gels (0.5% and 1.5% w/v) containing FITC-Dextrans (10, 70 and 500 kDa MW). Further validation was performed by a Monte Carlo approach, where we simulated the three-dimensional random walk of macromolecules in agar gel model. Diffusion coefficients were deduced from the mean square displacement curves and showed good agreements with those measured by iFRAP.