[논문]Honokiol에 의한 토끼의 무릎 연골세포에서 PI-3K/AKT pathway를 통하여 nitric oxide에 의해 유도되는 세포사멸의 억제

이원길; 김송자

doi:10.5352/jls.2010.20.10.1443

Honokiol에 의한 토끼의 무릎 연골세포에서 PI-3K/AKT pathway를 통하여 nitric oxide에 의해 유도되는 세포사멸의 억제
Honokiol Inhibits Nitric Oxide-Induced Apoptosis in Rabbit Articular Chondrocytes via PI-3K/AKT Pathway 원문보기

생명과학회지 = Journal of life science, v.20 no.10 = no.126, 2010년, pp.1443 - 1450

이원길 (공주대학교 자연과학대학 생명과학과) , 김송자 (공주대학교 자연과학대학 생명과학과)

초록
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Honokiol은 작은 분자량을 갖는 중국의 약초인 'Magnolia officinalis'에서 추출한 리간드로서 중국과 일본에서 전통 의약제로 사용되어 왔다. 이전 연구에서는 honokiol이 다양한 종류의 암에서anti-angiogenic, anti-invasive, anti-proliferative activities 등의 다양한 효과가 있는 것으로 알려져 있다. 우리는 이전 연구에서 Nitric oxide donor인 sodium nitroprusside (SNP)에 의해서 토끼 무릎관절연골세포에서 세포사멸이 일어나는 것을 보고하였다. 본 연구에서는 무릎 연골세포에서 NO에 의해 유도되는 세포사멸이 honokiol 처리농도에 의존적으로 억제되는 것을 세포형태, MTT assay, Western blot analysis 그리고 FACS를 통해 확인할 수 있었다. 또한, honokiol은 SNP에 의해 유도되는 p53의 발현 및 pro-caspase-3의 활성 저해, DNA fragmentation을 억제하였다. Honokiol에 의한 세포사멸 억제는 PI-3K의 특정 저해제인 LY294002를 SNP와 honokiol과 함께 처리하였을 때 세포의 사멸이 증가하는 것을 확인할 수 있었다. 이는 honokiol이 PI-3K/AKT pathway를 통하여 NO가 유도하는 세포사멸을 억제하는 것을 의미한다.

Abstract ▼ AI-Helper

Honokiol is a small molecular weight ligand originally isolated from the Chinese medicinal herb Magnolia officinalis, a plant used in traditional Chinese and Japanese medicine [9]. In a previous study, the effects of honokiol were shown to have anti-angiogenic, anti-invasive and anti-proliferative activities in a variety of cancers [1,3,4,11,13,17,24,29,30]. We showed previously that direct production of nitric oxide (NO) by treatment of NO donor, sodium nitroprusside (SNP), led to apoptosis in rabbit articular chondrocytes [15,16]. This study confirmed that NO-induced apoptosis was suppressed by honokiol treatment in a dose-dependent manner as determined by cell phenotype, MTT assay, Western blot analysis and FACS analysis in articular chondrocytes. Treatment of honokiol inhibited SNP-induced expression of p53 as well as DNA fragmentation in articular chondrocytes, but increased expressionof pro-caspase-3. Inhibition of SNP-induced apoptosis by honokiol treatment was rescued by LY294002, the specific inhibitors of phosphoinositide 3-kinase (PI-3K) in articular chondrocytes. Our results indicate that honokiol inhibits NO-induced apoptosis via PI-3K/AKT pathway in rabbit articular chondrocytes.

주제어

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문제 정의

However, the regulatory mechanism of NO-induced apoptosis has not been clearly elucidated yet. This study addressed the effects of honokiol on the regulation of NO-induced apoptosis by SNP, and suggests that inhibition of No-induced apoptosis by honokiol is required for PI-3 Kinase-dependent pathway.

제안 방법

To further investigate anti-apoptotic effects regulated by honokiol, LY294002, a well known signaling molecule upstream of PI-3K/AKT was treated in chondrocytes to block activation of PI-3K/AKT.

대상 데이터

33, 100 mM) in DMSO prepared and stored at 4℃ The following pharmacological agents were added 1 hr prior to honokiol, LY294002 to inhibit PI-3 kinase. LY294002 war obtained from BioMol (BioMol, PA).

데이터처리

A Student’s t-test was used to compare individual treatments with their respective control values.

이론/모형

The DNA content of 2×10⁴ cells in each group was analyzed by flow cytometer (Partec GmbH, Münster, Germany) and the results were demonstrated as histograms of DNA content. Quantification of the distinct cell cycle phases was calculated using the FloMax program.

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