참다랑어 골분이 흰쥐의 칼슘대사에 미치는 영향

김영만(Young Man Kim),윤군애(Gun Ae Yoon),황혜진(Hye Jin Hwang),지규용(Gyoo Yong Chi),손병일(Byoung Yil Son),배서영(Seo Young Bae),김인령(In Young Kim),정자영(Ja Young Chung) 한국식품영양과학회 2004 한국식품영양과학회지 Vol.33 No.1

우골대체 Ca 공급원으로서 참다랑어 골분과 이의 가공처리된 형태에 따른 Ca이용성을 흰쥐의 골격대사에 근거하여 비교하였다. 실험군은 ① 정상칼슘(0.5%)을 급여한 CC (CaCO₃; 대조군) ② TB(bluefin tuna bone powder) ③ CT (citrated bluefin tuna bone powder) ④ BB(bovine bone powder) ⑤ CL(calcium lactate, 유산칼슘) ⑥ 저칼슘을 급여한 LC(0.15% CaCO₃, 탄산칼슘)으로 구별하였다. 우골분을 섭취한 BB군의 체중 증가가 유의하게 높았으며, 구연산 처리된 참다랑어 골분(CT) 및 칼슘부족 식이를 급여한 LC군에서 체중증가가 낮았다. 식이 섭취량도 우골분(BB)군에서 가장 높았으며, 구연산처리된 참다랑어 골분(CT)군과 유산 칼슘(CL)군에서 유의하게 낮은 섭취량을 보였다. 저칼슘식이인 LC군은 변으로 배설되는 양이 다른 정상식이군에 비해 최소화되어 흡수율이 최고치를 나타냈으나 칼슘 보유량은 가장 낮았다. 뇨 칼슘배설량은 정상칼슘군 중 참다랑어 골분 (TB)군에서 유의하게 낮았고 유산칼슘(CL)군에서 높은 값을 보였지만 체내 칼슘보유량은 칼슘급원에 따른 차이를 보이지 않았다. 칼슘급원에 따른 변 칼슘 배설량과 칼슘흡수량은 차이가 없었다. 혈중의 calcitonin농도는 저칼슘군(LC)을 비롯한 탄산칼슘(CC)군과 유산칼슘(CL)군에서 유의하게 낮았으며, 참다랑어골분(TB)군, 구연산처리된 참다랑어골분 (CT)군, 우골분(BB)군에서는 높은 수치를 보였고, PTH와 osteocalcin 농도는 실험군 간에 차이를 보이지 않았다. 뇨의 DPD 수치는 LC군(저칼슘식이군)에서 유의하게 높았고, 정상수준의 칼슘을 섭취한 각 군에서는 차이를 나타내지 않았다. 대퇴골의 습윤무게는 참다랑어골분(TB)군과 구연산처리된 참다랑어 골분(CT)군에서 높은 수치를 나타내었고, 건조 후의 무게는 저칼슘군(LC)을 제외한 정상수준의 칼슘 투여군 간에 차이가 없었다. 대퇴골의 회분 함량은 정상수준의 칼슘식이군들에 비해 저칼슘식이인 LC군에서 유의하게 낮았다. 체중 100 g 당의 대퇴골의 칼슘함량은 저칼슘식이(LC) 군에서 유의적으로 낮았고 칼슘급원에 따라 차이를 나타내지 않았다. 대퇴골의 골밀도 측정 결과 저칼슘식이인 LC군은 정상식이군에 비해 골밀도가 유의하게 낮았으며, 동일한 정상수준의 칼슘이 공급된 실험군 사이에서는 참다랑어골분(TB)군의 골밀도가 가장 높은 수치를 보였다. 본 연구결과 여러 가지 칼슘급원에 따른 흰쥐의 골격대사는 큰 차이를 나타내지 않았으며, 저칼슘군과의 차이가 두드러져 양적인 면에서의 칼슘공급의 중요성을 지적할 수 있겠다. 대퇴골의 중량이나 회분, 칼슘 및 대퇴골의 골밀도 결과로 보아 참다랑어 골분은 탄산칼슘군이나, 기존에 칼슘 급원으로 사용해 오던 우골분수준으로 뼈의 건강유지 면에서 긍정적인 가치를 부여할 수 있는 것으로 사료된다. This study was conducted to examine the effect of bluefin tuna bone on the bone metabolism of the rats. Weaned 6-week old male rats were fed low-calcium diets for 2 weeks after the adjustment period. Rats were divided into 6 groups and were fed experimental diets for six weeks. Experimental groups were ① Normal calcium: CC (0.5% CaCO₃; control) ② TB (bluefin tuna bone powder) ③ CT (citrated bluefin tuna bone powder) ④ BB (bovine bone powder) ⑤ CL (calcium lactate) ⑥ Low calcium LC (0.15% CaCO₃). Low-calcium diet group (LC) showed the lowest calcium retention. There was no differences in calcium excretion in stool and calcium absorption among various calcium sources. Serum calcitonin levels were high in TB, CT and BB group compared to those in CC, CL LC group. Parathyroid hormone and osteocalcin levels showed no differences among experimental groups. Deoxypyridinoline (DPD) levels were significantly higher in LC group than in other groups. Wet weight of the femur were significantly high in TB and CT group, and dry weight of femur showed no differences among normal calcium groups. Bone density of femur in LC group was significantly lower than those of normal calcium feeding group, and TB group showed highest bone density among experimental groups. There was no differences in bone metabolism among various calcium sources. Therefore, it is pointed out that the amount of calcium intake is very important because there was significant differences between normal calcium diet and low calcium diet. According to the results of femur weight, ash, calcium and bone density, it is suggested that bluefin tuna bone have alternative effects to bovine bone powder on the maintenance of bone health.

Apoptotic Effect of Co-Treatment with a Natural Product, Chios Gum Mastic, and a Synthetic Chenodeoxycholic Acid Derivative, HS-1200, on Human Osteosarcoma Cells

Ji-Hak Min(민지학),Min-Jeong Kim(김민정),In-Ryoung Kim(김인령),Seung-Eun Lee(이승은),Hyun-Ho Kwak(곽현호),Gyoo-Cheon Kim(김규천),Hae-Ryoun Park(박혜련),Sang-Hun Shin(신상훈),Chul-Hoon Kim(김철훈),Na-Young Jeong(정나영),Hongsuk Suh 대한체질인류학회 2008 대한체질인류학회지 Vol.21 No.2

Chios gum mastic(CGM)은 그리이스 지역에서만 서식하는 Pistacia lenticulus 나무의 줄기와 잎에서 추출한 수지상의 천연 추출물이다. 합성 chenodeoxycholic acid(CDCA) 유E씨가 여러 가지 암세포에 유도한 세포자멸사 연구들이 보고되어져 왔다. 본 연구는 천연물질인 CGM과 항성 CDCA 유도체인 HS-1200의 병용처리가 사람골육종세포에 효과적인 상승 세포자멸사 효과가 있는지를 알기 위해서 수행되었다. CDM과 HS-1200의 병용처리가 단독처리에 비해서 효과적인 세포생존율 감소가 있는지 확인하기 위해서 MIT법을 시행하였고, 세포자멸사의 유도와 증가를 확인하기 위해서 Hoechst 염색법과 DNA 전기영동법을 사용하였다. 병용처리 때, 세포자멸사에 관계하는 단백질의 발현 변화와 세포내에서의 이동을 밝혀내기 위해서 Western bot 분석과 면역형광염색법을 수행하였다. 더 나아가서 proteasome 활성도와 사립체막 전위 변화를 측정하였다. 병용처리 된 사람골육종세포는 단독처리 된 사람골육종세포에서 거의 관찰할 수 없었던 많은 핵 응축, DNA 조각남, 사립체막 전위와 proteasome 활성도의 감소, DNA 양의 감소, cytochrome c의 세포질로의 유리, AIF와 DFF40(CAD)의 핵으로의 이동, caspase-7, caspase-3 그리고 PARP의 활성화와 같은 세포자멸사 증거를 보였다. 24시간 동안 40㎍/mL CGM과 25μM HS-1200을 각기 단독처리 한 결과에서는 세포자멸사를 유도 못했으나, 병용처리한 결과에는 아주 탁월한 세포자멸사의 유도를 보였다. 이러한 병용처리 결과는 사람골육종의 새로운 치료적 전략으로 응용될 수 있다고 생각한다. Chios gum mastic (CGM) is a resinous exudate obtained from the stem and the main leaves of Pistacia lenticulus tree native to Mediterranean areas. Recently it reported that CGM induced apoptosis in a few cancer cells in vitro. It has been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with a natural product, CGM and a CDCA derivative, HS-1200 on human osteosarcoma (HOS) cells. To investigate whether the co-treatment of CGM and HS-1200 compared with each single treatment efficiently reduced the viability of HDS cells, MTT assay was conducted. Induction and augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining and DNA hypoploidy, Westen blot analysis and immuno-fluorescent staining were performed to study the alterations of the expression level and translocation of apoptosis-related proteins in co-treatment. Furthermore, proteasome activity and mitochondrial membrane potential (MMP) change were also assayed. In this study, HOS cells co-treated with CGM and HS-1200 showed several lines of apoptotic manifestation whereas each single treated HOS cells did not. Although the single treatment of 40 ㎍/㎖, CGM or 25 μM HS-1200 for 24 h did not induce apoptosis, the co-treatment of them induced prominently apoptosis. Therefore our data provide the possibility that combination therapy of CGM and HS-1200 could be considered as a novel therapeutic strategy for human osteosarcoma.

Apoptotic Effect of Co-Treatment with Valproic Acid and 17AAG on Human Osteosarcoma Cells

박준영,박세진,김인령,박봉수,정성희,고명연,안용우,Park, Jun-Young,Park, Se-Jin,Kim, In-Ryoung,Park, Bong-Soo,Jeong, Sung-Hee,Ko, Myung-Yun,Ahn, Yong-Woo Korean Academy of Orofacial Pain and Oral Medicine 2011 Journal of Oral Medicine and Pain Vol.36 No.1

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent. And it is known that antitmor activity of VPA is associated with its targeted at histone deacetylases. 17AAG, Inhibition of HSP90 leads to the proteasome degradation of the HSP90 client proteins, such as Akt, Raf/Ras, Erk, VEGF, cyclin D and p53, and causes potent antitumor activity. It is reported that 17AAG-induced HSP90 inhibition results in prevention of cell proliferation and induction of apoptosis in several types of cancer. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and the HSP90 inhibitor, 17AAG on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and 17AAG showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-3, caspase-7 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or 0.5 ${\mu}M$ 17AAG for 48 h did not induce apoptosis, the co-treatment with them induced prominently apoptosis. Therefore our data in this study provide the possibility that combination therapy with VPA and 17AAG could be considered as a novel therapeutic strategy for human osteosarcoma.

Apoptotic Effect of Combination Treatment with a Proteasome Inhibitor, Lactacystin, and a Histone Deacetylase Inhibitor, Trichostatin A, on MCF-7 Cells

김규천(Gyoo-Cheon Kim),신유정(Yoo-Jung Shin),김인령(In-Ryeon Kim),이무형(Moo-Hyung Lee),황영섭(Young-Seob Hwang),길영기(Young-Gi Gil),박봉수(Bong-Soo Park) 대한해부학회 2006 Anatomy & Cell Biology Vol.39 No.6

Proteasome 저해제와 HDAC 저해제의 상호작용에 의한 상승효과가 여러 형태의 암에서 세포자멸사를 일으키는 연구가 많음에도 불구하고, 그 기작에 대해서는 거의 알려진 바가 없다. 본 연구는 proteasome 저해제인 lactacystin과 HDAC 저해제인 TSA의 병용처리가 세포자멸사 유도에 미치는 영향을 알아보고자 시행되었다. TSA를 전처리한 후 연이어 lactacystin을 처리한 군은 강한 항암효과와 핵의 응축현상을 보였다. Western blot 분석에서는 TSA와 lactacystin의 병용 처리는 Bax/Bcl-2 분율변화와 XIAP 수준의 감소 및 caspase-7의 활성화와 PARP의 분절의 결과를 얻었다. 그리고 더 나아가서 병용처리한 실험군에서 cell cycle arrest는 G2/M기에서 일어났으며, proteasome 활성은 사라졌다. 본 연구는 TSA와 lactacystin의 병용처리에 의해 일어나는 세포자멸사의 기작에 대해 설명하였고, 본 연구의 결과 자료는 생체의 항암치료전략에 도움을 줄 수 있을 거라고 생각한다. Although much information has been accumulated about the synergistic interaction of proteasome inhibitors and HDAC inhibitors to induce apoptosis in a certain type of cells, much less is known currently about the underlying mechanism. This study was undertaken to explore the combination effect of a histone deacetylase inhibitor, TSA, and a proteasome inhibitor, lactacystin, on the induction of apoptosis. Pretreatment of TSA and subsequent treatment of lactacystin showed the strong antitumor activity and nuclear condensation. Western blot assay showed that combination treatment of TSA and lactacystin increased Bax/Bcl-2 ratio and decreased level of XIAP. Activation of caspase-7 and cleavage of PARP were demonstrated after the combination treatment. In combination treatment group, cell cycle arrest was induced at G2/M phase and abolished increase in proteasome activity. This study is elucidating the mechanims whereby targeting apoptotic machineries may help in directing therapeutic strategies.

지속적 경막외진통법후 Pressure Algometer 에 의한 요통의 평가

권영은,박성희,김인령,이준학,이기남,문준일 예수병원 1997 예수병원학술지 Vol.18 No.-

국소마취중 Patient Controlled Sedation 을 위한Propofol 과 Midazolam 의 비교

이기남,박성희,권영은,이준학,김인령,문준일 대한마취과학회 1997 Korean Journal of Anesthesiology Vol.32 No.3

Background : Surgical procedures carried out under local anesthesia are associated with patient discomfort and apprehension. The purpose of this study is to compare propofol and midazolam with regard to their suitability for the patient controlled sedation (PCS) technique during local anesthesia. Methods : Forty unpremedicated, ASA physical status I day surgery patients undergoing elective minor surgery were randomly divided into two equal groups of patients who self-administered either propofol or midazolam intraoperatively. All patients initially received 0.5 g.kg-1 fentanyl. The bolus dose was either 20 mg (2 ml over 25 sec) of self-administered propofol or 0.5 mg (2 ml over 25 sec) of midazolam and lock-out period was 1 min. Results : The onset of sedation following propofol was significantly faster than midazolam (p$lt;0.05) and demands of propofol was significantly less than midazolam (p$lt;0.05). There were no significant differences for postoperative recovery, sedation and comfort scale. Conclusions : Propofol was judged the more suitable agent for PCS than midazolam, because of its more rapid onset of sedation and less demands of drug. (Korean J Anesthesiol 1997; 32: 457∼462)