7 709

Cited 0 times in

산화 스트레스에 의한 Thioredoxin의 발현과 폐암 조직에서의 발현

Other Titles
 Induction of thioredoxin by oxidative stress and overexpression of thioredoxin in lung cancer tissue 
Authors
 이장훈 
Issue Date
1998
Description
의학과/박사
Abstract
[한글]

활성산소종(reactive oxygen species)은 체내에서 정상 대사과정의 산물로 생성 될 뿐 아니라 대식 세포의 활성화 또는 생물이 방사선이나 일부 약제등의 생체이물(xenobiotics)에 노출되는 경우 발생한다 활성산소종은 DNA의 손상, 유전자 전사의 조절 및 원종양유전자(Proto-oncogenes)의 활성화를 통해 발암 개시에 관여한다. 대부분의 종양 세포주 및 종양 세포는 활성산소종을 생성하며 반면 종양 세포의 catalase, Mn- 및 CuZn-superoxid

e disinutase(SOD)등 항산화 단백의 활성도는 대부분 저하되어 있다. 이러한 조직내의 지속적인 산화 스트레스는 종양 침습 및 전이를 촉진한다.

Glutathione 및 glutaredoxin과 함께 세포내 산화환원 전위(redox potential)를 조절하는 12-kDa의 thioredoxin은 세포 활성, 증식, 분화 및 티올에 의한 아포토시스(thiol-mediated apoptosis) 조절에 관여한다. 최근 성인 T-세포 백혈병, 자궁 경부의 상피세포암 및 간세포암에서 thioredoxin의 양이 증가되어 있다는 보고가 있다.

따라서, 본 연구에서는 세포내 항산화 단백으로서 산화 스트레스에 의한 thioredoxin의 발현유도를 관찰하고 폐암 조직과 정상 조직을 비교하여 catalase, CuZn-SOD 및 glutathione peroxidase등 기존의 항산화 단백과 thioredoxin의 발현을 관찰하고 면역조직 화학적 검사를 통하여 폐암 조직내 thioredoxin의 발현을 관찰하여 다음과 같은 결과를 얻었다.

1. Thioredoxin의 양은 차이가 있었지만 대상으로 하였던 모든 조직에 thioredoxin이 존재 하였다.

2. Mouse monocyte-macrophage cells(RAW 264.7)에 5 mU/ml glucose oxidase 및 5μM menadione을 처치하였다. Thioredoxin의 발현은 12시간에 증가되어 48시간까지 지속되었으며 thioredoxin의 과발현이 glucose oxidase 보다 menadione을 처치한 경우 뚜렷하였다.

3. Immunoblot 검사상 thioredoxin의 발현은 폐암 조직에서 정상 폐조직과 비교하여 증가 하였으나 catalase 및 CuZn-SOD의 발현은 폐암 조직에서 정상 폐조직과 비교하여 감소 하였고 glutathione peroxidase의 발현 변화는 일정하지 않았다.

4. 면역조직화학적 검사상 주위 정상 조직에 비해 폐암 조직에서 thioredoxin의 발현이 증가해 있었다.

5. Thioredoxin이 여러 폐암 세포에 존재하였으나 다른 폐암 세포보다 소세포암 세포에 상대적으로 많이 존재하였다.

이상의 결과로 폐암 세포는 catalase, CuZn-SOD 및 glutathione peroxidase의 발현 감소로 지속적인 산화 스트레스에 노출되고 이러한 산화 스트레스는 폐암 세포의 thioredoxin 발현을 증가시키며 thioredoxin 발현 증가는 산화 스트레스에 의한 세포 파괴를 방어

하고 세포 증식을 통해 종양 성장에 관여하리라고 사료된다.

[영문]

Reactive oxygen species(0^^2 , H^^2 O^^2 , OH) are generated in vivo as byproducts of normal metabolism. They are also produced by activated phagocytes, and when organism is exposed to ionizing radiation, drugs capable of redox cycling or xenobiotics as well. Reactive oxygen species induce DNA damage, regulation of gene transcription and activation of proto-oncogenes that may lead to initiation of carcinogenesis. The most of carcinoma cell lines and carcinoma cells in tumor tissue produce reactive oxygen species. On the other hand, tumor cells are almost always low in catalase, Mn- and CuZn- superoxide dismutase(SOD) activity. Thus,

persistent oxidative stress in tumor tissue facilitate tumor invasion and metastasis.

12-kDa thioredoxin, which regulate the intracellular redox potential with glutathione and glutaredoxin, is involved in cell activation, proliferation, differentiation and thiol-mediated regulation of apoptosis. Recently, it was reported that adult T-cell leukemia, squamous cell carcinoma of uterine cervix, and hepatocellular carcinoma showed increased amounts of human thioredoxin.

In this study, the induction of thioredoxin, an intracellular antioxidant, was confirmed in the cell culture by giving oxidative stress, and the expression of thioredoxin and conventional antioxidant enzymes such as catalase, CuZn-SOD and

glutathione peroxidase were determined in lung cancer tissue, compared to paired lung tissue, by means of immunoblot analysis. The expression of thioredoxin was also observed in lung cancer tissue by immunohistochemical stain.

1. Although the amount of expressed thioredoxin was different, all tissues examined in this study showed immunoreactive bands.

2. Mouse monocyte-macrophage cells(RAW 264.7) were treated with 5 mU/ml glucose oxidase and 5 μM menadione. The expression of thioredoxin was increased at 12 hours after treatment with free radical generating system and sustained to 48 hours. The overexpression of thioredoxin wvas more prominent in menadione treatment than glucose oxidase treatment.

3. On immunoblot analysis, the expression of thioredoxin was increased in lung cancer tissue compared to normal tissue. However the expression of catalase and CuZn-SOD were decreased in lung cancer tissue compared to normal tissue. The expression of glutathione peroxidase was not consistent in tissues tested.

4. On immunohistochemical stain, the thioredoxin was intensely immunoreactive in lung cancer tissue compared to adjacent normal tissue.

5. Although thioredoxin was found in various lung cancer cells, the amount of thioredoxin in small cell carcinoma cells was relatively larger than that of the other cells.

In conclusion, it was confirmed that the oxidative stress could induce the thioredoxin, and it was also observed that lung cancer cells expressed high amount of thioredoxin whereas conventional antioxidant enzymes were reduced. Therefore it can be suggested that increased expression of thioredoxin in cancer cells would involve, in part, in tumor growth by cell proliferation and block of apoptosis.
Full Text
https://ymlib.yonsei.ac.kr/catalog/search/book-detail/?cid=CAT000000005590
Files in This Item:
제한공개 원문입니다.
Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 3. Dissertation
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/125733
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links