• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.394-402
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• 2003

This study was designed to investigate the protective effect of Bojungmyunyuk-dan(BJMY-Dan) on the cisplatin-induced cytotoxicity of primary rat astrocytes. BJMY-Dan is an oriental herbal prescription for its ability to recover protective effects against anti-cancer chemotherapies. After astrocytes were treated cisplatin, MTT assay was performed for cell viability test. To explore the mechanism of cytotoxicity, I used the several measures of apoptosis to determine whether this processes was involved in cisplatin-induced cell damage in astrocytes. Also, astrocytes were treated with BJMY-Dan and then, followed by the addition of cisplatin. Cisplatin decreased the viability of astrocytes in a dose and time-dependent manner. BJMY-Dan increased the viability of astrocytes treated cisplatin. Astrocytes treated cisplatin were revealed as apoptosis characterized by nuclear staining and flow cytometry. BJMY-Dan protected astrocytes from cisplatin-induced nuclear fragmentation and chromatin condensation. Also, caspase-3 and caspase-9 proteases were activated in astrocytes by cisplatin. BJMY-Dan inhibited the activation of caspase proteases in cisplatin-treated astrocytes. Cleavage of [poly(ADP-ribose) polymerase](PARP) was occurred at 12hr after treatment of cisplatin in astrocytes. BJMY-Dan recovered the cleavage of PARP in cisplatin-treated astrocytes. Also, BJMY-Dan inhibited the activation of pro-apoptotic factor, Bak by cisplatin. Lastly, astrocytes stained with JC-1 and Rhodamine 123 were photographed by fluorescence microscope to visualize changes of mitochondrial membrane permeability transition(MPT) during treatment with cisplatin for 24hr. BJMY-Dan recovered the change of MPT by cisplatin in astrocytes. According to above results, BJMY-Dan may protect astrocytes from cytotoxicity induced by chemotherapeutic agents, including cisplatin.

• International Journal of Oral Biology
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• v.34 no.1
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• pp.7-14
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• 2009

Nitric oxide (NO) acts as an intracellular messenger at the physiological level but can be cytotoxic at high concentrations. The cells within periodontal tissues, such as gingival and periodontal fibroblasts, contain nitric oxide syntheses and produce high concentrations of NO when exposed to bacterial lipopolysaccharides and cytokines. However, the cellular mechanisms underlying NO-induced cytotoxicity in periodontal tissues are unclear at present. In our current study, we examined the NO-induced cytotoxic mechanisms in human gingival fibroblasts (HGF). Cell viability and the levels of reactive oxygen species (ROS) were determined using a MTT assay and a fluorescent spectrometer, respectively. The morphological changes in the cells were examined by Diff-Quick staining. Expression of the Bcl-2 family and Fas was determined by RT-PCR or western blotting. The activity of caspase-3, -8 and -9 was assessed using a spectrophotometer. Sodium nitroprusside (SNP), a NO donor, decreased the cell viability of the HGF cells in a dose- and time-dependent manner. SNP enhanced the production of ROS, which was ameliorated by NAC, a free radical scavenger. ODQ, a soluble guanylate cyclase inhibitor, did not block the SNP-induced decrease in cell viability. SNP also caused apoptotic morphological changes, including cell shrinkage, chromatin condensation, and DNA fragmentation. The expression of Bax, a member of the proapoptotic Bcl-2 family, was upregulated in the SNP-treated HGF cells, whereas the expression of Bcl-2, a member of the anti-apoptotic Bcl-2 family, was downregulated. SNP augmented the release of cytochrome c from the mitochondria into the cytosol and enhanced the activity of caspase-8, -9, and -3. SNP also upregulated Fas, a component of the death receptor assembly. These results suggest that NO induces apoptosis in human gingival fibroblast via ROS and the Bcl-2 family through both mitochondrial- and death receptor-mediated pathways. Our data also indicate that the cyclic GMP pathway is not involved in NO-induced apoptosis.

• Journal of Life Science
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• v.18 no.4
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• pp.522-529
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• 2008

High-temperature requirement A2(HtrA2) has been known as a human homologue of bacterial HtrA that has a molecular chaperone function. HtrA2 is mitochondrial serine protease that plays a significant role in regulating the apoptosis; however, the physiological function of HtrA2 still remains elusive. To establish experimental system for the investigation of new insights into the function of HtrA2 in mammalian cells, we first obtained $HtrA2^{+/+}$ and $HtrA2^{-/-}$ MEF cells lines and identified those cells based on the expression pattern and subcellular localization of HtrA2, using immunoblot and biochemical assays. Additionally, we observed that the morphological characteristics of $HtrA2^{-/-}$ MEF cells are different form those of $HtrA2^{+/+}$ MEF cells, showing a rounded shape instead of a typical fibroblast-like shape. Growth rate of $HtrA2^{-/-}$ MEF cells was also 1.4-fold higher than that of $HtrA2^{+/+}$ MEF cells at 36 hours. Furthermore, we verified both MEF cell lines induced caspsase-dependent cell death in response to apoptotic stimuli such as heat shock, staurosporine, and rotenone. The relationship between HtrA2 and heat shock-induced cell death is the first demonstration of the research field of HtrA2. Our study suggests that those MEF cell lines are suitable reagents to further investigate the molecular mechanism by which HtrA2 regulates the balance between cell death and survival.

• Korean Journal of Adult Nursing
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• v.13 no.1
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• pp.108-122
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• 2001

The cause of essential hypertension is yet unknown, but in general is caused by interaction of hereditary factors, diet, obesity, lack of exercise and stress. The aging process influences various physiological mechanism related to regulation of blood pressure. So elderly hypertensives have a tendancy to consider the disease as a result of the physiological aging process. This attitude causes many complications, worsening of the disease and even early death because of inappropriate care. In order to improve self-management of elderly hypertensives in this study the researcher examined the effect of blood pressure regulation by an education program that improves self-care behavior, through increasing self-efficacy. The education program consisted of group education on hypertension and self-care strategies, and encouraging and reinforcing self-efficacy resources such as verbal persuation, performance accomplishment and vicarious experiences. A quasi-experimental pre-and post-test design was used. Thirty-two elderly hypertensives participated in the study. Eighteen in the education group and fourteen in the control group. The education program consisted of eight sessions twice a week for four weeks. There was no intervention for the control group. Data were analysed using SPSS for Windows(Version 8.0). The results were as follows. 1. There was a significant decrease in systolic and diastolic blood pressure between the experimental group and control group over three different times, and interaction by groups and over time. 2. There was no significant difference in the level of self-care behavior between the experimental group and control group over three different times, and interaction by groups and over time. 3. There was significant difference in selfefficacy of experimental and control group, depending on the measuring period, but there was no difference between these groups on interaction by groups and over time. 4. There was positive correlation between self efficacy and self care behavior depending on the measuring period. There was negative correlation between diastolic blood pressure and self-care behavior on the posttest of the program, and between systolic blood pressure and self-care behavior on the follow-up test of the program. Findings indicate that this study will contribute to develop nursing strategies for the regulation of blood pressure for the elderly, which is easy for the elderly to learn as a nonpharmacologic approach.

• Korean journal of applied entomology
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• v.61 no.1
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• pp.91-100
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• 2022

Ticks are the arthropod vector capable of transmitting diverse pathogens, which include bacteria, viruses, protozoan and fungi. Ticks are able to survive under stressful environmental conditions. One of evolutionary outcomes of these obligatory hematophagous arthropods is the survival for extended periods of time without a blood meal during off-host periods. Water conservation biology and heat tolerance have allowed ticks to thrive even under high temperatures and low relative humidity, thus they have become highly successful arthropods as they are distributed globally. Tick osmoregulatory physiology is a complex mechanism, which involves multiple osmoregulatory organs (salivary glands, Malpighian tubules, hindgut and synganglion) for the acquisition and excretion of water and ions. Blood feeding and water vapor uptake have been early reported as the primary passages for ixodid tick to acquire water. Recently, we have learned that ticks can actively drink environmental water allowing hydration. The acquired water can be traced to the salivary glands (type I acini) and the midgut diverticula. This opens new avenues for tick management through the delivery of toxic agents into their drinking water, in addition to an alternative strategy for the study of tick physiology. Here we address the osmoregulatory physiology in the ixodid ticks as a potential target physiological mechanism for tick control. We discuss the implications of water drinking behavior for tick control through the delivery of toxic agents and discuss the dermal excretion physiology as an additional pathway to induce tick dehydration and tick death.

• Journal of Korean Medical classics
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• v.11 no.1
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• pp.416-512
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• 1998

The following conclusions are obtained from the studies on the chapters concerning phisiology, pathology, daily conduct, materia medica, pulse, and urinalysis from , of the "Four Tantras". 1. The theoretical basis forming the Tibetan Medicine is the substance of phlegm, bile, and wind each of which is divided into five kinds. These phisiological substances can be transformed into pathological factors when certain environment is formed. 2. In embryology, the semen of the father and menstral blood of mother is considered the most important condition in conception, and the Five factors are regarded as important. There is a detailed explanation of development of the fetus while it stays in the womb of mother during 38weeks, such as the formation of the viscera, channels, sense organs, etc. 3. There is metaphor which compares the human body with the king's palace. With the development of human anatomy, there is the detailed anatomical picture of anterior and posterior aspects of human body. And also there is the measurement of physiological constitution and the three fluids. 4. In division of the channels, they concerned the now of the blood and distribution of the nerve fibers, and each channel is connected with one another. The division of the cannel is namely embryonic channel, channel of existence, channel of connection, and the course of life principle. 5. The seven bodily constituents and three factors of phlegm, bile, and wind are important in sustaining the life of human body as well as growth and maturization, and when their equilibrium is broken, the human body is degnerated, and finally death comes. 6. The signs of death is divided into distant sign, remote sign, certain sign. and uncertain sign, and is used as a clue in diagnosis of the disease. Especially there is a mention about the mechanism of the dreams, and different dreams according to the condition of the patient. 7. In pathology, there is the cause of the disease, the environmental factors which can induce disease, the path by which disease come into the human body, the characteristics of the disease, and the kinds of disease. 8. There is a mention about the conduct, and it is divided into the daily conduct, the mental attitude, and the side-effects which can occur when one puts up with the physiological actions of the body. 9. The daily diet is divided into food and beverage. The food is divided again into grain, meat, fat, boiled food, and spiced food, and the beverage into milk, water, and wine. 10. The pulsation should be taken in lift hand to diagnose heart, small intestine, stomach, spleen, kidney, reproductive organ, and in right hand jungs, large intestine, liver, gall bladder, kidney, and bladder. In the healthy person, the pulse moves 5times in one perspiration, and the type of pulse is constant while the pulse moves 100times. But unhealthy person's pulse is different from this. The urinalysis is the unique part of Tibetan Medicine, and is important in examination of the disease. One should decide which of the three factors are dominant by the obervation of the color, amount of the steam and how long it lasts, odour, foam, and the shape of the swirl in three different states when the urine is hot, warm, and cold. One can determine the life of the patient and which viscera is the cause of the disease by the pulse, and whether the nature of the disease is hot or cold by the urinalysis. 11. The materia medica contains gemstones, minerals, plateau medication, and meat products.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2002.07a
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• pp.113-113
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• 2002

Phylogenetically conserved Bcl-2 family proteins play a pivotal role in the regulation of apoptosis from virus to human. Members of the Bcl-2 family consist of antiapoptotic proteins such as Bcl-2, Bcl-xL, and Bcl-w, and proapoptotic proteins such as BAD, Bax, BOD, and Bok. It has been proposed that anti- and proapoptotic Bcl-2 proteins regulate cell death by binding to each other and forming heterodimers. A delicate balance between anti- and proapoptotic Bcl-2 family members exists in each cell and the relative concentration of these two groups of proteins determines whether the cell survives or undergoes apoptosis. Mcl-1 (Myeloid cell :leukemia-1) is a member of the Bcl-2 family proteins and was originally cloned as a differentiation-induced early gene that was activated in the human myeloblastic leukemia cell line, ML-1 . Mcl-1 is expressed in a wide variety of tissues and cells including neoplastic ones. We recently identified a short splicing variant of Mcl-1 short (Mcl-IS) and designated the known Mcl-1 as Mcl-1 long (Mcl-lL). Mcl-lL protein exhibits antiapoptotic activity and possesses the BH (Bcl-2 homology) 1, BH2, BH3, and transmembrane (TM) domains found in related Bcl-2 proteins. In contrast, Mcl-1 S is a BH3 domain-only proapoptotic protein that heterodimerizes with Mcl-lL. Although both Mc1-lL and Mcl-lS proteins contain BH domains fecund in other Bcl-2 family proteins, they are distinguished by their unusually long N-terminal sequences containing PEST (proline, glutamic acid, serine, and threonine) motifs, four pairs of arginine residues, and alanine- and glycine-rich regions. In addition, the expression pattern of Mcl-1 protein is different from that of Bcl-2 suggesting a unique role (or Mcl-1 in apoptosis regulation. Tankyrasel (TRF1-interacting, ankyrin-related ADP-related polymerasel) was originally isolated based on its binding to TRF 1 (telomeric repeat binding factor-1) and contains the sterile alpha motif (SAM) module, 24 ankyrin (ANK) repeats, and the catalytic domain of poly(adenosine diphosphate-ribose) polymerase (PARP). Previous studies showed that tankyrasel promotes telomere elongation in human cells presumably by inhibiting TRFI though its poly(ADP-ribosyl)action by tankyrasel . In addition, tankyrasel poly(ADP-ribosyl)ates Insulin-responsive amino peptidase (IRAP), a resident protein of GLUT4 vesicles, and insulin stimulates the PARP activity of tankyrase1 through its phosphorylation by mitogen-activated protein kinase (MAPK). ADP-ribosylation is a posttranslational modification that usually results in a loss of protein activity presumably by enhancing protein turnover. However, little information is available regarding the physiological function(s) of tankyrase1 other than as a PARP enzyme. In the present study, we found tankyrasel as a specific-binding protein of Mcl-1 Overexpression of tankyrasel led to the inhibition of both the apoptotic activity of Mel-lS and the survival action of Mcl-lL in mammalian cells. Unlike other known tankyrasel-interacting proteins, tankyrasel did not poly(ADP-ribosyl)ate either of the Mcl-1 proteins despite its ability to decrease Mcl-1 proteins expression following coexpression. Therefore, this study provides a novel mechanism to regulate Mcl-1-modulated apoptosis in which tankyrasel downregulates the expression of Mcl-1 proteins without the involvement of its ADP-ribosylation activity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.5
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• pp.1025-1034
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• 2002

The herbal extract (YMT_02) is a modified herbal extracts from Yukmijihwang-tang (YMJ) to promote memory-enhancing. The YMJ extracts has been widely used as an anti-aging herbal medicine for hundred years in Asian countries. The purpose of this study is to; 1) quantitatively evaluate the memory-enhancing effect of YMT_02 by behavior task, 2) identify candidate genes responsible for enhancing memory by cDNA microarray and 3) assess the anti-oxidant effect of YMT_02 on PC12 cell. Memory retention abilities are addressed by passive avoidance task with Sprague-Dawley (SD) male rat. Before the training session, the rats are subdivided into four groups and administrated with YMT_02, Ginkgo biloba, Soya lecithin and normal saline for 10 days. The retention test was performed. 24 hours after the training session. The retention time of the YMT_02 group was significantly (p<0.05) delayed (～100%), whereas Ginkgo biloba and Soya lecithin treatment delayed 20% and 10% respectively. The hippocampi of YMT_02 and control group were dissected and mANA was further purified. After synthesizing cDNA using oligo-dT primer, the cDNA were applied to Incyte rat GEMTM 2 cDNA microarray. The microarray results show that prealbumin(transthyretin), phosphotidylethanolamine N-methyltransferase, and PEP-19 are expressed abundantly in the YMT_02 treated group. Especially, PEP-19 is a neuron-specific protein, which inhibits apoptotic processes in neuronal cell. On the other hand, transcripts of RAB15, glutamate receptor subunit 2 and CDK108 are abundant in control group. Besides, neuronal genes involved in neuronal death or neurodegeneration such as neuronal-pentraxin and spectrin are abundantly expressed in control group. Additionally, the YMT_02 shows an anti oxidative effect in the PC12 cell. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the memory-enhancing effect of herbal extracts YMT_02, for example, anti-apoptotic, anti-oxidative, and neuroprotective effects.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.891-897
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• 2007

This experimental Study was designed to investigate the mechanism of Acanthopanacis Cortex Roots(ACR) 50% ethyl alcohol extract on the improvement of regional cerebral blood flow and cytokines production in cerebral ischemic rats. And was designed to investigate whether ACR inhibits lactate dehydrogenase(LDH) activity in neuronal cells The results were as follows; ACR significantly inhibited LDH activity in neuronal cells. These results suggest that ACR prevents the neuronal death. rCBF was significantly and stably increased by ACR(10 mg/kg, i.p.) during the period of cerebral reperfusion, which contrasted with the findings of rapid and marked increase in control group. In cytokine production of serum by drawing from femoral arterial blood at 1 hr after middle cerebral arterial occlusion, experimental group was significantly decreased $IL-1{\beta}$ and $TNF-{\alpha}$ production, and significantly increased IL-10 production compared with control group. In cytokine production of serum by drawing from femoral arterial blood at 1 hr after reperfusion, experimental group was significantly decreased $IL-1{\beta}$ and $TNF-{\alpha}$ production, and significantly increased IL-10 production compared with control group. According to above results, the author suggest that ACR had an anti-ischemic effect through the improvement of cerebral hemodynamics, and inhibitive effect on the brain damage by inhibited $IL-1{\beta}$ and $TNF-{\alpha}$ production, and accelerated IL-10 production.

• Journal of Physiology & Pathology in Korean Medicine
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• v.29 no.1
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• pp.18-26
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• 2015

Akebiae Caulis is a galenical originated from Akebia quinata Decaisne species. It is commonly used in the treatment of oposiuria, inflammation, nociceptive and fever. Here, we investigated the effect of Akebiae Caulis extract (ACE) to protect hepatocyte against the malfunction of mitochondria and apoptosis. Arachidonic acid (AA)+iron promoted excessive reactive oxygen species (ROS) production and exerted a deleterious effect on mitochondria. Treatment with ACE protected hepatocytes from AA+iron-induced cytotoxicity, as shown by alterations in the protein levels related with apoptosis such as poly(ADP-ribose) polymerase, pro-caspase 3, Bcl-XL and Bcl-2. Moreover, AA+iron-induced $H_2O_2$ production, GSH depletion and mitochondrial dysfunction were alleviated by ACE pretreatment. As a potential molecular mechanism for the ACE-mediated cytoprotection, phosphorylation of AMP-activated protein kinase (AMPK), a key regulator in determining cell survival or death, was increased by ACE. Moreover, ACE treatment enhanced inactive phosphorylation of glycogen synthase kinase-$3{\beta}$ ($GSK3{\beta}$), downstream substrate kinase of AMPK. More importantly, ACE prevented a decrease in the $GSK3{\beta}$ phosphorylation derived by AA+iron, which might contribute to mitohondiral protection and cell survival. To further identify essential compounds in Akebiae Caulis for the protection of AA+iron-mediated cytotoxicity, we found that betulin in combination with hederagenin protected from AA+iron-induced mitochondrial dysfunction. Betulin+hederagenin treatment also increased inactive phosphorylation of $GSK3{\beta}$ in common with ACE. These results suggest that ACE protected hepatocytes against oxidative stress and mitochondrial dysfunction, which is mediated with inactive $GSK3{\beta}$ phosphorylation downstream of AMPK.