1,25(OH)₂-23ene-D₃ : in vitro에서 U937 세포의 증식과 분화 및 in vivo에서 쥐의 칼슘대사에 미치는 영향

정수자(Soo-Ja Jung),서명자(Myung-Ja Suh) 한국식품영양과학회 1995 한국식품영양과학회지 Vol.24 No.1

1,25(OH)₂-23ene-D₃는 23번과 24번 탄소 사이에 이중결합을 가진 새로운 비타민 D₃ 유도체로서 이 화합물의 항악성 효과를 검토하기 위하여 in vitro에서 U937 세포(human histiocytic lymphoma cell line)의 증식과 분화에 대한 효과 및 in vivo에서 쥐의 칼슘대사에 미치는 영향을 관찰하였다. 본 연구에서 1,25(OH)₂-23ene-D₃의 효과는 비타민 D₃의 자연 대사물인 1α, 25-dihy-droxycholecalciferol [1,25(OH)₂D₃]과 비교 검토하였다. 1,25(OH)₂-3ene-D₃는 1,25(OH)₂D₃에 비해 U937 세포 증식억제 및 분화촉진에 강한 효과가 있음이 확인되었고, 특히 superoxide 생성과 nonspecific esterase (NSE) 활성으로 측정한 세포의 분화촉진 효과는 1,25(OH)₂D₃에 비해 20배 이상 높은 것으로 나타났다. 또한 1,25(OH)₂-23ene-D₃로 처리된 U937 세포는 N/C비 감소, 배양말기에 부착세포수 증가 등의 현상을 나타내면서 분화에 따른 세포형태 변화를 더욱 뚜렷히 보였다. 쥐에 이들 비타만 D₃ 유도체를 투여한 결과 1,25(OH)₂-23ene-D₃는 hypercalcemia와 hypercalciuria를 야기시키는 활성이 1,25(OH)₂D₃에 비해 50배 이상 낮음이 확인되었다. 1,25(OH)₂-23ene-D₃가 칼슘대사에 미치는 활성이 낮으면서 U937 세포의 증식과 분화에 직접적인 강한 효과를 가지고 있음이 밝혀짐에 따라 앞으로 백혈병 환자나 건선(psoriasis)등의 피부성 질환을 가진 환자의 임상연구에 이용이 가능한 화합물이라 생각된다. 1,25(OH)₂-23ene-D₃ is a novel vitamin D₃ analog which has a double bond between C-23 and C-24. We describe the effects of this analog on cell differentiation and cell proliferation in vitro using the human histiocytic lymphoma cell line U937, and on calcium metabolism in rats in vivo. In the present investigation 1,25(OH)₂-23ene-D₃ was compared to the natural metabolite of vitamin D₃, 1α, 25-dihydroxycholecalciferol [1,25(OH)₂-D₃]. 1,25(OH)₂-23ene-D₃ was more potent than 1,25(OH)₂D₃ for inhibition of proliferation and induction of differentiation of U937 cells. Especially, its effect on induction of differentiation, as measured by superoxide production and nonspecific esterase(NSE) activity, was about 20-fold more potent than 1,25(OH)₂D₃. This analog morphologically and functionally differentiated U937 cells to monocyte-macrophage phenotype showing a decrease of N/C ratio in Giemsa staining and the increase of adherence ability to surface. Intraperitoneal administration of 1,25(OH)₂-23ene-D₃ to rats showed that the compound had at least 50 times less activity than 1,25(OH)₂D₃ in causing hypercalcemia and hypercalciuria. The strong direct effects of 1,25(OH)₂-23ene-D₃ on cell proliferation and cell differentiation, coupled with its decreased activity of calcium metabolism make this compound an interesting candidate for clinical studies including patients with leukemia, as well as several skin disorders, such as psoriasis.

Human 백혈병 세포에 대한 비타민 D₃ 유도체의 항암효과 및 Human 임파구의 면역기능에 대한 비타민 D₃ 유도체의 역할

정수자(Soo-Ja Jung) 한국식품영양과학회 1998 한국식품영양과학회지 Vol.27 No.1

1,25(OH)₂-16ene-23yne-D₃는 비타민 D₃의 활성형인 1,25-dihydroxyvitamin D₃[1,25(OH)₂D₃, calcitriol]의 유도체로서 이 유도체의 항암효과를 검토하기 위해 U937 세포(human histiocytic lymphoma cell line)에 대한 증식억제와 분화촉진 효과를 검토하였다. 한편 이 유도체의 면역조절기능을 확인하기 위해 phytohemagglutinin(PHA)에 의해 활성화된 peripheral blood lymphocytes(PBLs)에 의한 IFN-γ 생성에 대한 이 유도체의 영향을 검토하였다. 본 연구에서 1,25(OH)₂-16ene-23yne-D₃는 모체인 1,25(OH)₂D₃와 비교 검토하였다. U937 세포에 대한 증식억제와 분화촉진에 관한 연구에서 1,25(OH)₂-16ene-23yne-D₃는 1,25(OH)₂D₃에 비해 강한 효과가 있음이 확인되었다. 특히 세포의 증식억제에 관한 연구에서 이 유도체는 1,25(OH)₂D₃에 비해 약 30배의 강한 효과가 있었으며, nonspecific esterase(NSE)활성으로 측정한 세포의 분화촉진 효과도 1,25(OH)₂D₃ 보다 탁월하였다. 1,25(OH)₂-16ene-23yne-D₃로 처리된 U937 세포는 N/C비 감소, 배양 말기에 부착하는 세포수의 증가 등의 현상을 나타내면서 분화에 따른 세포형태 변화를 뚜렷이 보여주고 있다. 배양 3일 후 PHA로 활성화된 PBLs에 의한 IFN-γ 생성저하는 1,25(OH)₂D₃에 비해 1,25(OH)₂-16ene-23yne-D₃에 의해 뚜렷이 나타났다. PBLs에 의한 IFN-γ 생성저하는 이 유도체에 의해 농도 의존형으로 나타났으며 특히 10^(-7)M에서는 대조군(배양액에 PHA만 넣어 배양한 세포)에 비해 11% 정도의 IFN-γ 생성을 보여주고 있다. 이와같이 본 연구에서 1,25(OH)₂-16ene-23yne-D₃는 U937 세포에 대한 증식억제와 분화촉진에 강한 효과를 나타내어 있으며 또한 PBLs에 의한 IFN-γ 생성억제에도 강한 작용을 나타내고 있음이 확인됨에 따라 이 화합물은 백혈병 환자나 건선(psoriasis) 등의 여러 가지 악성질환에 대한 임상연구의 활용에 어느정도 기여하리라 생각되며, 또한 본 연구의 결과는 면역조절작용에서 이 화합물의 역할을 밝히는 근거가 되리라 생각한다. This study describes the effects of 1,25-dihydroxyvitamin D₃[1,25(OH)₂D₃, calcitriol] analog, 1,25(OH)₂-16ene-23yne-D₃ on proliferation and differentiation of the human histiocytic lymphoma cell line U937. This paper also describes the effects of 1,25(OH)₃-l6ene-23yne-D₃ on γ-interferon(IFN-γ) synthesis by phytohemagglutinin-activated peripheral blood lymphocytes(PBLs). In the present investigation, 1,25(OH)₂-l6ene-23yne-D₃ was compared to the natural metabolite of vitamin D₃, 1,25 (OH)₂D₃. 1,25(OH)₂-l6ene-23yne-D₃ was more potent than 1,25(OH)₂D₃ for inhibition of proliferation and induction of differentiation of U937 cells. Its effects on inhibition of proliferation was about 30- fold more potent than 1,25(OH)₂D₃. On induction of differentiation as measured by nonspecific esterase (NSE) activity and morphologic change, this analog morphologically and functionally differentiated U937 cells to monocyte-macrophage phenotype showing a decrease of N/C ratio in Giemsa staining and the increase of adherence ability of surface. After 3 days in culture, a more significant supression of IFN-γ synthesis by PBLs was achieved with 1,25(OH)₂-l6ene-23yne-D₃ than with 1,25(OH)₂D₃. The effects of this analog on supression of IFN-γ synthesis was a dose-dependent manner, with peak activity at 10^(-7)M. The strong direct effects of 1,25(OH)₂-l6ene-23yne-D₃ on cell proliferation and cell differentiation, make this compound an interesting candidate for clinical studies for several types of malignancies, and the effects on supression of IFN-γ synthesis provide the further evidence for a role of 1,25(OH)₂-16ene-23yne-D₃ in immunoregulation.

Effects of a New 1,25(OH)₂ - Vitamin D₃ Analog on Proliferation and Differentiation of the Human Histiocytic Lymphoma Cell Line U937

정수자(Soo-Ja Jung),서명자(Myung-Ja Suh),류병호(Beung-Ho Rhu) 한국식품영양과학회 1994 한국식품영양과학회지 Vol.23 No.3

인체 histiocytic lymphoma cell line U937의 증식억제 및 분화촉진 효과에 대한 새로운 vitamin D₃ 유도체인 1,25(OH)₂-16ene-23yne-26,27-F^6-D₃의 영향을 관찰하였다. 10^(-7)M 및 10^(-8)M 농도에서 이 화합물은 U937 cells의 증식을 각각 87% 및 62%까지 억제시켰다. 분화촉진 효과에 관한 연구에서는 세포의 morphology 변화와 세포분화의 marker로써 이용되는 nonspecific esterase(NSE) activity 및 배양기 세포의 adherence abilty를 검토한 결과 이화합물은 U937 cells을 macrophage으로 분화시킴이 확인되었다. 또한 10^(-7)M 농도에서 이화합물은 U937 cells의 c-myc mRNA expression을 60% 정도 감소시킴이 확언되어 1,25(OH)₂-16ene-23yne-26,27-F^6-D₃는 U937 cells에 대해 분화를 유도하는 factor임을 본 연구 결과 알 수 있다. This study describes the effects of a novel 1,25-dihydroxyvitamin D₃ analog [1,25(OH)₂-16ene-23yne-26,27-F_(6)-D₃] on proliferation and differentiation of the human histiocytic lymphoma cell line U937 in vitro. We also examined the expression of c-myc oncogene in U937 cells. Growth of U937 cells was apparently inhibited to 62% and 87% of the control level after 4 days in the presence of 10^(-8)M and 10^(-7)M of this analog, respectively. This compound morphologically and functionally differentiated U937 cells to monocyte-macrophage phenotype showing the increase of adherence ability to surface and a decrease of N/C ratio in Giemsa staining. Especially, nonspecific esterase activity which is a marker of cell differentiation to monocyte-macrophage was positive, and production of the positive stained cells increased in a dose dependent fashion. The expression of c-myc oncogene by 1,25(OH)₂D₃ analog(10^(-7)M) was reduced by 60% at the mRNA level as determined by Northern blotting. The effects of this novel analog on cell proliferation and cell differentiation may open up new therapeutic strategies for human disorders such as psoriasis and may provide a tool to understand the mechanism of action of vitamin D₃ seco-steroids in malignancy.

원시에서 교정굴절력변화에 따른 착란원 크기

최운상(Woon Sang Choi),정수자(Soo Ja Jung) 한국안광학회 2000 한국안광학회지 Vol.5 No.1

A variable process of blur circle is calculated for a artificial hyperopia. The calculation is used to the value of Gullstrand`s theoretical eye and a method of geometrical optics. The theoretical eye simplified a entrance pupil and the retina. Ophthalmic lens and eye changed a equivalent lens. Refractive power of a equivalent lens is converted to focal length within theoretical eye, and this is calculated about relation of a blur circle on the retina and ophthalmic lens.

펄스형 방전플라스마에서 발생하는 가시광선의 분광 ( 2 )

최운상(Woon Sang Choi),정수자(Soo Ja Jung),김용훈(Yong Hun Kim),장준규(Jun Kyu Jang),정정복(Jung Bok Jung),신장철(Jang Cheol Shin) 한국안광학회 2000 한국안광학회지 Vol.5 No.2

We investigated visible light radiated from Plasma Focus device by time - integrated analyzed method. Plasma focus is a device that translated from electric energy into visible light by electric discharge. Spectral analysis is using Monochromator ( focal length = 0.5 m ) . Time - integrated spectrum is analyzed with densitometer the film which developed a constant range of wavelength. The condition of visible emission was that the discharging voltage was 13 kV and the working gas were Argon and Helium.

회전원판반응조에 의한 Pseudomonas putida H-5의 포름알데히드의 연속적 분해

류병호(Beung Ho Ryu),임복규(Bok Gyu Lim),김동석(Dong Seuk Kim),원용돈(Yong Don Weon),정수자(Soo Ja Jung) 한국생물공학회 1993 KSBB Journal Vol.8 No.1

Aspergillus awamori, B-2의 균사체 고정화 의한 Melanoidin 탈색

류병호(Beung-Ho Ryu),김혜성(Hye-Sung Kim),하미숙(Mi-Suk Ha),정종순(Jong-Sun Jung),빈재훈(Jae-Hun Bin),이영숙(Young-Sook Lee),정수자(Soo-Ja Chung) 한국식품영양과학회 1989 한국식품영양과학회지 Vol.18 No.1

곰팡중에서 melanoidin의 탈색력이 있는 Aspergillus awamori, B-2을 선별하여 탈색력을 실험하였다. Aspergillus awamori, B-2는 3.0% glucose, 0.5% yeast extract, 0.1% KH₂PO₄ 및 0.05% MgSO₄ㆍ7H₂O을 함유하는 melanoidin 용액(pH 7.0) 에서 5일 동안 37℃에서 배양했을 때 가장 높은 탈색력을 나타내었다. 탈색력을 효과적으로 하기 위하여 Ca - alginate로 고정화하여 최적조건에서 계속적으로 탈색하였을대 mycelia 단독보다는 더욱 효과적이었다. Melanoidin 탈색력은 최적 조건에서 10일 동안 반응하였을때 약 70%을 나타내었다. 고정화한 mycelia의 재사용에 의한 계속적인 탈색을 시도하였던바 15일 동안 연속적으로 반응시켜도 약 60-70%의 탈색력을 계속 유지하였다. Aspergillus awamori, B-2 which has a high ability to decolorize melanoidin was selected among various fungi.<br/> Aspergillus awamori, B-2 showed the highest decolorization activity when it was cultivated in a melanoidin medium containing 3.0% glucose, 0.5% yeast extract, 0.1% KH₂PO₄and 0.05 % MgSO₄ㆍ7H₂O at an initial pH 7.0 at 37℃ for 5 days.<br/> Mycelia immobilized system with Ca-alginate was more effective on melanoidin decolorization activity showed approximately 70% in 10 days under the optimal conditions.<br/> Continuous decolorzation of melanoidin using reuse of immobilized mycelia showed an almost constant decolorization of abort 60-70 % for 15 days.

Pseudomonas putida H-5에 의한 포름알데히드의 생분해

류병호(Beung Ho Ryu),임복규(Bok Gyu Lim),김동석(Dong Seuk Kim),원용돈(Yong Don Weon),정수자(Soo Ja Jung) 한국생물공학회 1993 KSBB Journal Vol.8 No.1

Ethanol 발효를 위한 내열성 효모 균주의 Screening

류병호(Beung - Ho Ryu),남기두(Ki - Du Nam),김혜성(Hae - Sung Kim),김동석(Dong - Seuk Kim),지영애(Young Ae Ji),정수자(Soo - Ja Jung) 한국미생물생명공학회 1988 한국미생물·생명공학회지 Vol.16 No.4

표고버섯 열수 추출물이 발암원을 급여한 흰쥐의 간 기능 관련 효소활성에 미치는 영향

최미연,정수자,임상선 한국식품영양학회 1998 韓國食品營養學會誌 Vol.11 No.1

This study was designed to observe the effects of hot water soluble polysaccharides extract(PS) from Lentinus edodes on the enzyme activities related with hepatic function and peroxidation in the rats fed butter yellow. The four groups of male SD rats were fed with the diets contained 15% casein(basal diet ; NO group), added butter yellow(BO group) or/and PS(NP, BP group) for 6 weeks. The activities of γ-GTP and GPT in BP were significantly lower compared with BO. The activities of glutathione peroxidase, catalase and lactate dehydrogenase were not significantly different between NP and NO, while those activities were significantly lower value in BP than BO. The activities of glutathione S-transferase of the microsomal and cytosol fractions were significantly low in BP than in BO. The contents of glutathione and malondialdehyde in the liver were considerably low value in BP. In a view of these results the PS of Lentinus edodes prevents the lipid peroxidation and diminishes the liver toxicity caused with butter yellow. The superoxide dismutase activity in cytosolic fraction of liver was not found any effect in all groups. But hepatic function enzyme activities such as catalase and glutathione peroxidase, LDH activities were remarkably decreased in the groups 2(basal diet + PS) and the γ-GTP, GOT and GPT activities, too. In liver, the contents of glutathione decreased by PS supplementation but HDL-cholesterol and total cholesterol ratio in plasma decreased at the groups 3, 4. The γ-GTP, GOT and GPT in plasma were remarkably higher in the rats fed the p-DAB than the control group, too. But above enzyme activities significantly decreased in the groups fed PS.