정지형 자전거 운동 훈련이 건강한 여성의 체구성,심폐기능 및 유연성에 미치는 효과

김동옥,최정숙,안혜영,민혜숙,이경숙,박연환,송미령,최명애,최정안,김매자 서울대학교 간호대학 간호과학연구소 1999 간호학 논문집 Vol.13 No.1

The purpose of this study was to determine the changes in body composition, cardiopulmonary function, and flexibility following 8 weeks' bicycle ergometer exercise training. The subjects of this research consisted of healthy adult women between 30 and 40 years of age. Initial intensity of bicycle ergometer exercise was based on the target heart rate equivalent to 55% of maximal oxygen uptake, and intensity of the exercise increased by 5% every 2 weeks. Body composition, cardiopulmonary function at rest and during maximal exercise, as well as flexibility were determined before and after 8 weeks of bicycle ergometer exercise training. Masimal exercise was performed on the treadmill according to Bruce Protocol. The results obtained were as follows; 1. There were o changes in body weight, percent body fat, fat body weight, and lean body weight as well. The ventilation volume for 1 minute, respiratory quotient and expired CO₂ volume have not changed significantly after the training, either. 2. As a result of training, resting systolic and diastolic blood pressure decreased significantly(p<.05) 3. Maximal heart rate, maximal oxygen consumption and maximal running time increased significantly after the training(p<.05) 4. Pelvic flexibility increased slightly after the training, however, it did not reach the statistical significance. Trunk flexion forward increased significantly after the training(p<.05). From these results, it may be concluded that 8 weeks bicycle ergometr training improve the cardiopulmonary function and flexibility in healthy adult women between 30-40 years of age.

Antiestrogen Interaction with Estrogen Receptors and Additional Antiestrogen Binding sites in Human Breast Cancer MCF-7 Cells

Ahn, Mee-Ryung,Sheen, Yhun-Yhong The Pharmaceutical Society of Korea 1997 Archives of Pharmacal Research Vol.20 No.6

To gain further insight into the mechanism of action of antiestrogens, we examined the interaction of antiestrogen with the estrogen receptor system and with estrogen- noncompetable antiestrogen binding sites. In addition to binding directly to the estrogen receptor, antiestrogens can be found associated with binding sites that are distinct from the estrogen receptor. In contrast to the restriction of estrogen receptors to estrogen target cells, such as those of uterus and mammary glands, antiestrogen binding sites are present in equal amounts in estrogen receptor-positive and -negative human breast cancer cell lines, such as MCF-7, T47D, and MDA-MB-231 that differ markedly in their sensitivity to antiestrogens. In order to gain greater insight into the role of these antiestrogen binding sites in the action of antiestrogens, we have examined the biopotency of different antiestrogens for the antiestrogen binding sites and that is CI628 > tamoxifen > trans-hydroxy tamoxifen > CI628M > H1285 > LY117018. This order of affinities does not parallel the affinity of these compounds for the estrogen receptor nor the potency of these compounds as antiestrogens. Indeed, compounds with high affinity for the estrogen receptor and greatest antiestrogenic potency have low affinities for these antiestrogen binding sites. Antiestrogenic potency correlates best with estrogen receptor affinity and not with affinity for antiestrogen binding sites. In summary, our findings suggested that interaction with the estrogen receptor is most likely the mechanism through which antiestrogens evoke their growth inhibitory effects.

Trichostatin A, a Histone Deacetylase Inhibitor Stimulate CYP3A4 Proximal Promoter Activity in Hepa-I Cells

Mee Ryung Ahn,Dae-Kee Kim,Yhun Yhong Sheen 대한약학회 2004 Archives of Pharmacal Research Vol.27 No.4

Cytochrome P450 3A4 (CYP3A4) is the most abundant CYPs in human liver, comprising approximately 30% of the total liver CYPs contents and is involved in the metabolism of more than 60% of currently used therapeutic drugs. However, the molecular mechanisms underlying regulation of CYP3A4 gene expression have not been understood. Thus, this study has been carried out to gain the insight of the molecular mechanism of CYP3A4 gene expression, investigating if the histone deacetylation is involved in the regulation of CYP3A4 gene expression by proximal promoter. Also SXR was investigated to see if they were involved in the regulation of CYP3A4 proximal promoter activity. Hepa-I cells were transfected with a plasmid containing ~1 kb of the human CYP3A4 proximal promoter region (863 to +64 bp) cloned in front of a reporter gene, luciferase, in the presence or absence of SXR. Transfected cells were treated with CYP3A4 inducers such as rifampicin, PCN and RU 486, in order to examine the regulation of CYP3A4 gene expression in the presence or absence of trichostatin A (TSA). In Hepa-I cells, CYP3A4 inducers increased modestly the luciferase activity when TSA was cotreated, but this increment was not enhanced by SXR cotransfection. Taken together, these results indicated that the inhibition of histone deacetylation was required to SXR-mediated increase in CYP3A4 proximal promoter region when rifampicin, or PCN was treated. Further a trans-activation by SXR may demand other species-specific transcription factors.

Trichostatin A, a Histone Deacetylase Inhibitor Stimulate CYP3A4 Proximal Promoter Activity in Hepa-I Cells

Ahn Mee Ryung,Kim Dae-Kee,Sheen Yhun Yhong The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.4

Cytochrome P450 3A4 (CYP3A4) is the most abundant CYPs in human liver, comprising approximately $30\%$ of the total liver CYPs contents and is involved in the metabolism of more than $60\%$ of currently used therapeutic drugs. However, the molecular mechanisms underly-ing regulation of CYP3A4 gene expression have not been understood. Thus, this study has been carried out to gain the insight of the molecular mechanism of CYP3A4 gene expression, investigating if the histone deacetylation is involved in the regulation of CYP3A4 gene expression by proximal promoter. Also SXR was investigated to see if they were involved in the regulation of CYP3A4 proximal promoter activity. Hepa-1 cells were transfected with a plasmid containing ${\~}1kb$ of the human CYP3A4 proximal promoter region (863 to +64 bp) cloned in front of a reporter gene, luciferase, in the presence or absence of SXR. Transfected cells were treated with CYP3A4 inducers such as rifampicin, PCN and RU 486, in order to examine the regulation of CYP3A4 gene expression in the presence or absence of trichostatin A (TSA). In Hepa-1 cells, CYP3A4 inducers increased modestly the luciferase activity when TSA was co-treated, but this increment was not enhanced by SXR cotransfection. Taken together, these results indicated that the inhibition of histone deacetylation was required to SXR-mediated increase in CYP3A4 proximal promoter region when rifampicin, or PCN was treated. Further a trans-activation by SXR may demand other species-specific transcription factors.

Expression of Human Liver 3,4-Catechol estrogens UDP-Glucuronosyltransferase cDNA in COS 1 Cells

Ahn, Mee-Ryung,Owens, Ida-S.,Sheen, Yhun-Yhong The Pharmaceutical Society of Korea 1997 Archives of Pharmacal Research Vol.20 No.5

The human cDNA clone UDPGTh2, encoding a liver UDP-glucuronosyltransferase (UDPGT), was isolated from a .gamma.gt 11 cDNA library by hybridization to mouse transferase cDNA clone, UDPGTm1. The two clones had 74% nlicleotide sequence identities in the coding region. UDPGTh2 encoded a 529 amino acid protein with an amino terminus membrane-insertion signal peptide and a carboxyl terminus membrane-spanning region. In order to establish substrate specificity, the clone was inserted into the pSVL vector (pUDPGTh2) and expressed in COS 1 cells. Sixty potential substrates were tested using cells transfected with pUDPGTh2. The order of relative substrate activity was as follows: 4-hydroxyestrone > estriol >2-hydroxyestriol > 4-hydroxyestradiol > $6{\alpha}$-hydroxyestradiol >$5{\alpha}$-androstane-$3{\alpha}$, $11{\beta}$, $17{\beta}$-triol=5${\beta}$-androstane-$3{\alpha}$ ${\beta}$, $17{\beta}$-triol. There were only trace amounts of gulcuronidation of 2-hydroxyestradiol and 2-hydroxyestrone, and in contrast to other cloned transferase, no gulcuronidation of either the primary estrogens and androgens (estrone, $17{\beta}$estradiol/testosterone, androsterone) or any of the exogenous substrates tested was detected. A lineweaver-Burk plot of the effect of 4-hydroxystrone concentration on the velocity of glucuronidation showed an apparent Km of $13{\mu}M$. The unique specificity of this transferase might play an important role in regulating the level and activity of these potent and active estrogen metabolites.

Trichostatin A, a Histone Deacetylase Inhibitor Stimulate CYP3A4 Proximal Promoter Activity in Hepa-I Cells

Ahn, Mee-Ryung,Kim, Dae-Kee,Sheen, Yhun-Yhong 이화여자대학교 약학연구소 2004 藥學硏究論文集 Vol.- No.14

Cytochrome P450 3A4 (CYP3A4) is the most abundant CYPs in human liver, comprising approximately 30% of the total liver CYPs contents and is involved in the metabolism of more than 60% of currently used therapeutic drugs. However, the molecular mechanisms underlying regulation of CYP3A4 gene expression have not been understood. Thus, this study has been carried out to gain the insight of the molecular mechanism of CYP3A4 gene expression, investigating if the histone deacetylation is involved in the regulation of CYP3A4 gene expression by proximal promoter. Also SXR was investigated to see if they were involved in the regulation of CYP3A4 proximal promoter activity. Hepa-l cells were transfected with a plasmid containing ~1 kb of the human CYP3A4 proximal promoter region (863 to +64 bp) cloned in front of a reporter gene, luciferase, in the presence or absence of SXR. Transfected cells were treated with CYP3A4 inducers such as rifampicin, PCN and RU 486, in order to examine the regulation of CYP3A4 gene expression in the presence or absence of trichostatin A (TSA). In Hepa-l cells, CYP3A4 inducers increased modestly the luciferase activity when TSA was cotreated, but this increment was not enhanced by SXR cotransfection. Taken together, these results indicated that the inhibition of histone deacetlyation was required to SXR-mediated increase in CYP3A4 proximal promoter region when rifampicin, or PCN was treated. Further a trans-activation by SXR may demand other species-specific transcription factors.

Expression of Human Liver 3, 4-Catechol Estrogens UDP-Glucuronosyltransferase cDNA in COS 1 Cells

Ahn, Mee Ryung,Owens, Ida S.,Sheen, Yhun Yhong 梨花女子大學校 藥學硏究所 1998 藥學硏究論文集 Vol.- No.7

The human cDNA clone UDPGTh2, encoding a liver UDP-glucuronosyltransferase (UDPGT), was isolated from a λgt 11 cDNA library by hybridization to mouse transferase cDNA clone, UDPGTm1. The two clones had 74% nucleotide sequence identities in the coding region UDPGTh2 encoded a 529 amino acid protein with an amino terminus membrane-insertion signal peptide and a carboxyl terminus membrane-spanning region. In order to establish substrate specificity, the clone was inserted into the pSVL vector (pUDPGTh2) and expressed in COS 1 cells. Sixty potential substrates were tested using cells transfected with pUDPGTh2. The order of relative substrate activity was as follows: 4-hydroxyestrone > estriol >2-hydroxyestriol > 4-hydroxyestradiol > 6α-hydroxyestradiol > 5α-androstane-3α, 11β, 17β-triol=5β-androstane-3α, 11β, 17β-triol. There were only trace amounts of gulcuronidation of 2-hydroxyestradiol and 2-hydroxyestrone, and in contrast to other cloned transferase, no gulcuronidation of either the primary estrogens and androgens (estrone, 17β-estradiol/testosterone, androsterone) or any of the exogenous substrates tested was detected. A lineweaver-Burk plot of the effect of 4-hydroxyestone concentration on the velocity of glucuronidation showed an apparent Km of 13μM. The unique specificity of this transferase might play an important role in regulating the level and activity of these potent and active estrogen metabolites.

Antiestrogen Interaction with Estrogen Receptors and Additional Antiestrogen Binding Sites in Human Breast Cancer MCF-7 Cells

Ahn, Mee Ryung,Sheen, Yhun Yhong 梨花女子大學校 藥學硏究所 1998 藥學硏究論文集 Vol.- No.7

To gain further insight into the mechanism of action of antiestrogens, we examined the interaction of antiestrogen with the estrogen receptor system and with estrogen- noncompetable antiestrogen binding sites. In addition to binding directly to the estrogen receptor, antiestrogens can be found associated with binding sites that are distinct from the estrogen receptor, In contrast to the restriction of estrogen receptors to estrogen target cells, such as those of uterus and mammary glands, antiestrogen binding sites are present in equal amounts in estrogen receptor-positive and -negative human breast cancer cell lines, such as MCF-7, T47D, and MDA-MB-231 that differ markedly in their sensitivity to antiestrogens. In order to gain greater insight into the role of these antiestrogen binding sites in the action of antiestrogens, we have examined the biopotency of different antiestrogens for the antiestrogen binding sites and that is CI628 > tamoxifen > trans-hydroxy tamoxifen > CI628M > H1285 > LY117018. This order of affinities does not parallel the affinity of these compounds for the estrogen receptor nor the potency of these compounds as antiestrogens. Indeed, compounds with high affinity for the estrogen receptor and greatest antiestrogenic potency have low affinities for these antiestrogen binding sites. Antiestrogenic potency correlates best with estrogen receptor affinity and not with affinity for antiestrogen binding sites. In summary, our findings suggested that interaction with the estrogen receptor is most likely the mechanism through which antiestrogens evoke their growth inhibitory effects.

IN2001 Regulates CYP3A4 Gene Expression in Hep G2 Cells

Ahn, Mee-Ryung,Kim, Dae-Kee,Sheen, Yhun-Yhong Korean Environmental Mutagen Society 2004 한국환경성돌연변이·발암원학회지 Vol.24 No.4

Cytochrome P4503A4(CYP3A4) is the most abundnat CYPs in human liver, comparising approximately 30% of the total liver CYPs contents ans is involbed in the metabolism of more than 60% of currently used therapeutic drugs. The expression of CYP3A4 is induced by a variety of structurally unrelated xonobiotics including the antibiotic rifampicin and endogenous hormones, and might be mediated through steroid and xenobiotic receptor(SXR) system. The molecular mechanisms underlying regulation of CYP3A4 gene expression hae not been understood. In order to gain the insight of the molecular mechanism of CYP3A4 gene expression, study has been undertaken to investigate if the histone deacelylation is involved in the regulation of CYP3A4 gene expression by proximal promoter or not. Also SXR was investigated to see if they were involved in the regulation of CYP3A4 proximal promoter activity. HepG2 or Hena-I cells were transfected with a plasmid containing~1kb of the CYP3A4 proximal promoter region (-863 to +64bp) cloned in front of a reporter gene, luciferase, in the presence or absence of SXR or hER. Transfected cells were treated with CYP3A4 inducers such as rifampicin, PCN and RU 486, or with estradiol, in order to exmine to regulation of CYP3A4 gene expression in the presence or absence of trichostatin A (TSA). In HepG2 cells, CYP3A4 inducers and estradiol increased significantly the luciferase activity by CYP3A4 proximal promoter, only when TSA was co-treated after SXR cotransfection. In the case of Hepa-I cells CYP3A4 inducers and estradiol incressed modestly the luciferase activity when TSA was co-treated, but this increment was not enhanced by SXR cotransfection in contrast to HepG2 cells. Taken together, these results indicated that the inhibition of histone deacetylation was required to SXR-mediated increase in CYP3A4 proximal promoter region when rifampicin, or PCN was treated. Futher a trans-activation by SXR may demand other species-specific transcription factors.

Evaluation on Drug Variations

Mee Ryung Ahn 大韓藥學會 2004 大韓藥學會 總會 및 學術大會 Vol.2004 No.1