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뇌신경세포에서 tPA에 의한 MMP의 발현 조절에 관한 연구
고운철(Woon-Chul Ko),이선령(Sun-Ryung Lee) 한국생명과학회 2009 생명과학회지 Vol.19 No.6
뇌졸중 치료에 사용되는 tPA는 탁월한 혈전 용해 효과를 보이고 있어 혈액의 흐름을 용이하게 하는데 중요한 역할을 한다. 그러나 tPA 치료법은 매우 짧은 시간 내에 사용해야하는 단점과 출혈, 부종과 같은 여러 가지 부작용이 수반될 수 있기 때문에 매우 제한적이다. 이전의 실험 결과에 따르면 tPA의 이러한 양면적인 현상은 MMP의 활성 조절과 관련이 있는 것으로 보고되어 있으나 세포시스템을 활용한 이들의 직접적인 효과나 조절 기전에 대한 연구는 거의 알려져 있지 않다. 본 연구는 임상에서 사용되는 tPA의 부정적인 효과를 극복하기 위한 방안을 모색하고자 tPA와 MMP 활성과의 조절 기전을 살펴보았다. 랫트의 뇌로부터 추출한 신경세포에서 tPA의 처리는 MMP의 발현을 촉진시켰고 저산소상태에서 tPA에 의한 MMP활성 증가가 더욱 가속화되었으며 JNK 신호전달 경로를 통해 조절되는 것을 확인하였다. Tissue plasminogen activator (tPA) is very useful for dissolving the clots of blood, however, the use of tPA is limited to only 3-5% of ischemic stroke patients because of the narrow therapeutic time windows and negative side effects. Previous evidences suggest that limitation of tPA in thrombolytic therapy may be related to the upregulation of MMPs. However, little is known about the regulatory mechanism. In this study, we examined the role of tPA on MMP upregulation in rat neuronal cells. tPA (5 ㎍/㎖) increased MMP-9 levels of neuronal cells in a time dependent manner. Hypoxia/reoxygenation amplified tPA-induced MMP-9 levels significantly. Pretreatment with JNK inhibitor SP600125 reduced the MMP-9 response. These results suggest that tPA can upregulate MMPs in neuronal cells and that JNK kinase may be involved.
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화학적 저산소증이 유도하는 뇌신경세포 손상에 있어서 미성숙 진귤 과피 발효 추출물의 보호 효과
고운철(Ko, Woon Chul),이선령(Lee, Sun Ryung) 한국영양학회 2015 Journal of Nutrition and Health Vol.48 No.5
Purpose: Neuronal apoptotic events induced by aging and hypoxic/ischemic conditions is an important risk factor in neurodegenerative diseases such as ischemia stroke and Alzheimer"s disease. The peel of Citrus sunki Hort. ex Tanaka has long been used as a traditional medicine, based on multiple biological activities including anti-oxidant, anti-inflammation, and anti-obesity. In the current study, we examined the actions of fermented C. sunki peel extract against cobalt chloride (CoCl₂)-mediated hypoxic death in human neuroblastoma SH-SY5Y cells. Methods: Cell viability was measured by trypan blue exclusion. Expression of apoptosis related proteins and release of cytochrome c were detected by western blot. Production of intracellular reactive oxygen species (ROS) and apoptotic morphology were examined using 2",7"- dichlorofluorescin diacetate (DCF-DA) and 4",6-diamidino-2-phenylindole (DAPI) staining. Results: Exposure to CoCl₂, a well-known mimetic agent of hypoxic/ischemic condition, resulted in neuronal cell death via caspase-3 dependent pathway. Extract of fermented C. sunki peel significantly rescued the CoCl₂-induced neuronal toxicity with the cell viability and appearance of apoptotic morphology. Cytoprotection with fermented C. sunki peel extract was associated with a decrease in activities of caspase-3 and cleavage of poly (ADP ribose) polymerase (PARP). In addition, increase in the intracellular ROS and release of cytochrome c from mitochondria to the cytosol were inhibited by treatment with extract of fermented C. sunki peel. Conclusion: Based on these data, fermented C. sunki peel extract might have a protective effect against CoCl₂-induced neuronal injury partly through generation of ROS and effectors involved in mitochondrial mediated apoptosis.
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산유자 잎 에탄올 추출물의 미백, 주름억제, 항염증 및 항산화 효능
이재연 ( Jae Yeon Lee ),안은경 ( Eun Kyung Ahn ),고혜진 ( Hye Jin Ko ),조영락 ( Young Rak Cho ),고운철 ( Woon Chul Ko ),정용환 ( Yong Hwan Jung ),최경민 ( Kyung Min Choi ),최미래 ( Mi Rae Choi ),오좌섭 ( Joa Sub Oh ) 한국응용생명화학회 2014 Journal of Applied Biological Chemistry (J. Appl. Vol.57 No.4
In the present study, we investigated the biological activities of Xylosma congesta leaf ethanol extract (XCO) using a variety of in vitro and cell culture model systems for antimelanogenic, anti-wrinkle, anti-inflammatory and anti-oxidant activities. First, XCO markedly inhibited α-melanocyte stimulating hormone-stimulated melanin synthesis in B16F10 cells. Secondly, XCO marginally induced procollagen synthesis in CCD-986SK cells. Thirdly, XCO dose-dependently suppressed lipopolysaccharideinduced nitric oxide (NO) production in RAW 264.7 cells. XCO did not affect cell viability at different concentrations used in this study, indicating that XCO-mediated inhibition of melanin,procollagen and NO synthesis is not mediated by cytotoxicity. Finally, XCO was found to exert anti-oxidant effect. Taken together, these findings demonstrate for the first time that XCO possesses anti-melanogenic, anti-wrinkle, anti-inflammatory andanti-oxidant activities, and suggest further evaluation and development of XCO as a functional supplement or cosmetic that may be useful for whitening skin, reducing wrinkles and treating inflammatory responses.
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