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인체 폐암조직에서 Phospholipase C-$\gamma1$의 활성화 단백, AHNAK의 발현양상
오윤정,박준성,최소연,정성철,이선민,황성철,이이형,한명호,이기범,류한영,하만준,배윤수,이서구,Oh, Yoon-Jung,Park, Chun-Seong,Choi, So-Yeon,Cheong, Seong-Cheoll,Lee, Sun-Min,Hwang, Sung-Chul,Lee, Yi-Hyeong,Hahn, Myung-Ho,Lee, Kyi-Beom,Ryu, Han 대한결핵및호흡기학회 1999 Tuberculosis and Respiratory Diseases Vol.47 No.3
배경: Phospholipase C(PLC)는 세포의 성장, 분화, 변형(transformation)과 관련된 세포내 신호 전달과정에 중추적인 역할을 하는 효소이다. 이들 중 PLC-$\gamma$는 tyrosine kinase의 인산화에 의해 주로 활성화되는 데, 최근에 phosphatidic acid(PA), phosphatidy-linositol 3, 4, 5-trisphosphate($PIP_3$), tau 단백에 의한 활성화 기전이 밝혀진 바 있다. 특히 tau 단백은 bovine brain에서 arachidonic acid와 함께 PLC-$\gamma$를 활성화시키는 것으로 알려져 PLC-$\gamma$와 $PLA_2$ 사이의 cross-talk이 이루어질 가능성이 제시되고 있다. 최근 보고에 의하면 tau 단백과 같은 기전으로 PLC-${\gamma}1$ 활성화시키는 단백이 bovine lung에서 발견되었고, 이 활성화 단백을 정제 및 클론하여 AHNAK 단백임이 확인된 바 있다. 또한 PLC-${\gamma}1$이 유방암, 대장암, 위암 등에서 증가되어 있어 발암 과정과 연관되어 있음이 보고되어 왔으나 PLC-${\gamma}1$의 활성화 단백인 AHNAK 단백에 대해서는 질병과 관련되어 연구된 것이 아직 없는 실정이며 저자 등은 폐암 조직과 정상 폐조직에서 AHNAK 단백의 발현 양상을 연구하여 폐암의 발암과정에 AHNAK 단백이 관여함을 밝히고자 하였다. 대상 및 방법: 아주대학교 병원에 내원하여 폐암으로 수술을 받은 환자의 폐암 조직과 동일 환자의 정상 폐조직에서 AHNAK 단백의 발현양상을 western blot 분석과 면역조직화학적 염색방법을 통하여 조사하였다. 결과: 14예의 편평상피암 세포조직 중 8예 (57.1 %)와 14예의 선암 세포조직 모두에서 정상 대조군에 비해 AHNAK 단백의 발현이 증가하였고, 70 kDa~200kDa의 여러가지 분자량을 가지는 띠모양으로 나타났다. 면역조직화학적 염색에서도 정상 폐조직보다 폐암 조직내에서 강한 발색반응을 보였다. 결론: PLC-${\gamma}1$의 활성화 단백인 AHNAK 단백이 폐암 조직에서 정상 조직보다 과발현된 것은, AHNAK 단백이 PLC-${\gamma}1$을 활성화시켜 폐암의 발생 기전에 관여할 수 있음을 뒷받침한다고 하겠다. Background: Phospholipase C(PLC) plays a central role in cellular signal transduction and is important in cellular growth, differentiation and transformation. There are currently ten known mammalian isozymes of PLC reported to this date. Hydrolysis of phosphatidylinositol 4,5-bisphosphate($PIP_2$) by PLC produces two important second messengers, inositol 1,4,5-trisphosphate($IP_3$) and diacylglycerol. PLC-${\gamma}1$, previously, was known to be activated mainly through growth factor receptor tyrosine kinase. Other mechanisms of activating PLC-yl have been reported such as activation through tau protein in the presence of arachidonic acid in bovine brain and activation by $IP_3$, phosphatidic acid, etc. Very recently, another PLC-${\gamma}1$ activator protein such as tau has been found in bovine lung tissue, which now is considered to be AHNAK protein. But there has been no report concerning AHNAK and its associated disease to this date. In this study, we examined the expression of the PLC-${\gamma}1$ activator, AHNAK, in lung cancer specimens and their paired normal. Methods: From surgically resected human lung cancer tissues taken from twenty-eight patients and their paired normal counterparts, we evaluated expression level of AHNAK protein using immunoblot analysis of total tissue extract Immunohistochemical stain was performed with primary antibody against AHNAK protein. Results: Twenty-two among twenty-eight lung cancer tissues showed overexpression of AHNAK protein (eight of fourteen squamous cell lung cancers, all of fourteen adenocarcinomas). The resulting bands were multiple ranging from 70 to 200 kDa in molecular weight and each band was indistinct and formed a smear, reflecting mobility shift mainly due to proteolysis during extraction process. On immunohistochemistry, lung cancer tissues showed a very heavy, dense staining with anti-AHNAK protein antibody as compared to the surrounding normal lung tissue, coresponding well with the results of the western blot Conclusion: The overexpression of PLC-${\gamma}1$ activator protein, AHNAK in lung cancer may provide evidence that the AHNAK protein and PLC-${\gamma}1$ act in concerted manner in carcinogenesis.
기관지천식 환자에서 아스피린과 음식첨가물에 대한 과민성의 빈도
박해심(Hae Sim Park),조요한(Yo Han Cho),김선신(Sun Sin Kim),김희연(Hee Yeon Kim),남동호(Dong Ho Nahm),서창희(Chang Hee Suh),한명호(Myung Ho Hahn) 대한천식알레르기학회 1998 천식 및 알레르기 Vol.18 No.4
Objective and method: In order to identify the aggravating agents for intrinsic asthma, we performed ASA- and food additive-challenge tests on 182 subjects diagnosed as having intrinsic asthma. The following tests were performed: Lysine-aspirin bronchoprovocation test to confirm aspirin-sensitivity, sodium bi-sulfite (40-200mg) oral provocation test for sulfite sensitivity, tartrazine oral provocation test (50mg) for tartrazine sensitivity, and sodium benzoate (400mg) oral provocation test for sodium benzoate sensitivity. Positive reaction was defined as decrease in FEV, by more than 20% from the baseline value after the provocation. Result: Seventy-five (41.2%) of 182 subjects showed positive responses to more than one agent among the aspirin and three food additives challenged. The prevalence of aspirin-sensitivity was the highest (22.5%), followed by sulfite-sensitivity (8.8%), and then concurrent sensi- tivity to both aspirin and sulfite (6.0% ), to both aspirin and tartrazine (1.6% ), to aspirin, sulfite and tartrazine (1.1%) and to aspirin, sulfite and sodium benzoate (0.5%). Rhino-sinusitis was noted in 62.5% of aspirin-sensitive asthmatic subjects, 60% of sulfite-sensitive ones, and 80% of tartrazine-sensitive ones. Urticaria was noted in 21.4% of aspirin-sensitive asthmatic subjects, 16.6% of sulfite-sensitive ones and 6.3% of tartrazine-sensitive ones. Thirty-seven to 83% of positive responders had no adverse reaction history. Conclusion: These findings suggest that ASA and food additive challenge tests should be considered as a screening test to evaluate any aggravating factors in subjects with intrinsic asthma, even though they may not have experienced any adverse reactions.
원발성폐암 환자에서 말초혈액과 국소림프절 단핵구의 NK 및 LAK 활성도에 관한 연구
이이형(Yi Hyeong Lee),김세규(Se Kyu Kim),김형일(Hyung Il Kim),정경영(Kyoung Young Chung),장준(Joon Chang),김성규(Sung Kyu Kim),이원영(Won Young Lee),한명호(Myung Ho Hahn),윤정구(Jung Ku Youn) 대한내과학회 1998 대한내과학회지 Vol.54 No.3
Background: Several lymphocytic populations, such as natural killer(NK) cells and lymphokine-activated killer(LAK) cells, are involved in immunosurveillance against tumors. Whereas the biological significance of the regional lymph node as a tumor barrier remains unclear, the clinical prognostic relevance of the neoplastic infiltration of these nodes is accepted. It appears that lymph node metastasis are more frequent in lung cancer than in other cancers because of impaired defensive mechanisms in the regional lymph nodes. However little is known about the immunologic function of regional lymph node lymphocytes in patients with lung cancer. Although there is general agreement that the NK and LAK activities of peripheral blood mononuclear cells(PBMC) decreases in patients with various solid and leukemic tumors, this decrease remains unclear with regard to the NK and LAK activities of their regional lymph node mononuclear cells(LNMC). We performed this study to determine the NK and LAK activities of regional lymph node, and to compare with those of peripheral blood in patients with lung cancer. Methods: We measured the NK and LAK activities of PBMC and LNMC that were extirpated at lung cancer operations in 17 patients with lung cancer by 4 hour 51Cr-release assay using K562, Raji cell and allogenous lung cancer cell line(NCIH1092) as a target cell. BT ratio were 12.5:1, 25:1, and 50:l. Results: 1. Recombinant interleukin-2 induced strong cytotoxic activities against various target cells in PBMC and LNMC. 2. In patients with lung cancer, NK and LAK activities against K562 and allogenous lung cancer cell line(NCIH 1092) were lower than those of PBMC. 3. Against Raji cell, NK activities were not significantly different between PBMC and LNMC, but LAK activities were significantly lower than those of PRMC. 4. NK activities against K562, Raji, and NCIH1092 cell were not significantly different between in patients with early stage and advanced stage lung cancer. 5. LAK activities of PBMC and LNMC against K562, Raji, and NCIH1(62 cell were significantly lower in patients with advanced stage than those in patients with early stage lung cancer. Conclusion: NK and LAK activities of LNMC in patients with lung cancer were lower than those of PBMC, but the cytotoxicity was markedly increased after culture with rIL-2.
방사선 조사후 손상된 백서 폐조직에서의 Thioredoxin Peroxidase의 발현
정성철 ( Seong Cheoll Cheong ),박준성 ( Joon Seong Park ),박지원 ( Jee Won Park ),이선민 ( Sun Min Lee ),박광주 ( Kwang Joo Park ),황성철 ( Sung Chul Hwang ),이이형 ( Yi Hyeong Lee ),한명호 ( Myung Ho Hahn ),오영택 ( Young Taek 대한결핵 및 호흡기학회 1999 Tuberculosis and Respiratory Diseases Vol.47 No.5