알러젠 제거 옻나무 추출물이 종양 전이 억제에 미치는 영향

박재현,문구,Park, Jae-Hyun,Moon, Goo 대한암한의학회 2010 大韓癌韓醫學會誌 Vol.15 No.1

Objective : The aim of this present study is to evaluate the inhibitory effect of allergen removed Rhus verniciflua (ARV) on Matrix Metalloproteinase-9 (MMP-9), Matrix Metalloproteinase-2 (MMP-2) which is considered to have a clinically important role in tumor metastasis. Methods : The inhibitory effects of standardized extract of ARV on the MMP-2, MMP-9 were investigated by spectrofluorometer while the inhibitory effects on the active MMP-2, pro MMP-2, pro MMP-9 were investigated by zymography. Antimetastatic effect of standardized extract of ARV was investigated in vitro on human fibrosarcoma cell (HT1080)'s invasion through Matrigel. Results : The standardized extract of ARV showed inhibitory effects on the active MMP-2 (IC50, $1.01{\mu}g$/ml), active MMP-9 (IC50, $2.5{\mu}g$/ml) depending on concentrations which was determined by spectrofluorometer. The standardized extract of ARV showed inhibitory effects on the active MMP-2, pro MMP-2, pro MMP-9 depending on concentrations which was determined by zymography. However its inhibitory effect on pro MMP-9 was relatively weaker rather than active MMP-2, pro MMP-2. The standardized extract of ARV showed inhibitory effects in vitro on human fibrosarcoma cell (HT1080)'s invasion through Matrigel according to concentration. Conclusions : These results indicate that standardized extract of ARV has antimetastatic effect through inhibit again MMP-2, MMP-9. Also its inhibitory effect is more powerful on active MMP-2, pro MMP-2 than on active MMP-9, pro MMP-9. It is necessary to conduct further studies on other MMP families, TIMP, and each component of standardized extract of ARV.

난소암 세포주들의 전이능력과 Type Ⅳ collagenase 효소 활성화의 비교

이상형(SH Lee),배석년(SN Bae),김재동(JD Kim),박종섭(JS Park),김승조(SJ Kim) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.5

Our purpose in this study was to detect the secretory pattern and the degree of enzymatic activity of MMP-2 and to evaluate the invasive activty in vitro in each cancer cell line, using four kinds of human ovarian cancer cell lines (CAOV-4, SW626, NIH: OVCAR-3, and SK-OV-3) as well as MCF-7MMP-2 cell line which secretes recombinant 72-kDa MMP-2 as an inactive form. The results were as follows; 1. An inactive form of MMP-2 was secreted by all ovarian cancer cell lines, but the activated form of MMP-2 was also secreted by NIH: OVCAR-3, SK-OV-3, and SW626. 2. In the Boyden chamber chemoinvasion assay, the invasive activity was shown in SK-OV-3, NIH: OVCAR-3, SW626, and CAOV-4 cell lines in order. This finding corresponds with the secretory pattern of 62 kDa MMP-2, activated form. 3. In the outgrowth morphology on Matrigel, the dendritic processes of NIH: OVCAR-3 and SK-OV-3 cell lines were seen to emerge more actively than those of SW626 and CAOV-4 cell lines. NIH: OVCAR-3 and SK-OV-3 cell lines also had a clustered formation. 4. An inactive form of MMP-2 secreted by CAOV-4 was activated by the treatment with Concanavalin A, MMP-2 activator. 5. The productions and secretions of MMP-2 in SK-OV-3, NIH: OVCAR-3, and SW626 cell lines were inhibited by the treatment with cycloheximide, MMP-2 inhibitor. From the above results, we showed that the invasion and metastasis of human ovarian cancr cell lines have directly relations with MMP-2. It was identified that the secretory patterns of activated MMP-2 were closely associated with the invasiul activity of human ovarian cancer cell lines in vitro and that the MMP-2 secreted by human ovarian cancer cell lines might been activated or inhibited by enzyme regulators. In the future, we wish this study applied to the metastatic prevention and treatment of human ovarian cancer by using enzyme regulators.

The MMP-2 -735 C Allele is a Risk Factor for Susceptibility to Breast Cancer

Yari, Kheirollah,Rahimi, Ziba,Moradi, Mohamad Taher,Rahimi, Zohreh Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Background: The expression of MMP genes has been demonstrated to be associated with tumor invasion, metastasis and survival rate for a variety of cancers. The functional promoter polymorphism MMP-2 C-735T is associated with decreased expression of the MMP-2 gene. The aim of present study was to detect any association between MMP-2 C-735T and susceptibility to breast cancer. Materials and Methods: The MMP-2 C-735T polymorphism was studied in 233 women (98 with breast cancer and 135 healthy controls). All studied women were from Kermanshah and Ilam provinces of Western Iran. The MMP-2 C-735T polymorphism was detected using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The frequencies of MMP-2 CC, CT and TT genotypes in healthy individuals were 59.3, 38.5 and 2.2%, respectively. However, in breast cancer patients, only CC (71.4%) and CT (28.6%) genotypes were observed (p=0.077). In patients the frequency of the MMP-2 C allele was significantly higher (85.7%) compared to that in controls (78.5 %, p=0.048). The presence of C allele of MMP-2 increased the risk of breast cancer by 1.64-fold [OR=1.64 (95%CI 1.01-2.7, p=0.049)]. The frequency of MMP-2 C allele was also higher in patients ${\leq}40$ years (88.9%) than those aged ${\geq}41$ years (67.5%, p=0.07). In addition, the frequency of MMP-2 C allele tended to be higher in patients with a family history of cancer in first-degree relatives (76.6%) compared to that without a family history of cancer (67.3%, p=0.31). Conclusions: Our findings indicate that the C allele of MMP-2 C-735T polymorphism is associated with increased risk of breast cancer. Also, the MMP-2 C allele might increase the risk of young onset breast cancer in our population.

Type I Collagen-induced Pro-MMP-2 Activation is Differentially Regulated by H-Ras and N-Ras in Human Breast Epithelial Cells

Kim, In-Young,Jeong, Seo-Jin,Kim, Eun-Sook,Kim, Seung-Hee,Moon, A-Ree Korean Society for Biochemistry and Molecular Biol 2007 Journal of biochemistry and molecular biology Vol.40 No.5

Tumor cell invasion and metastasis are often associated with matrix metalloproteinases (MMPs), among which MMP-2 and MMP-9 are of central importance. We previously showed that H-Ras, but not N-Ras, induced invasion of MCF10A human breast epithelial cells in which the enhanced expression of MMP-2 was involved. MMP-2 is produced as a latent pro-MMP-2 (72 kDa) to be activated resulting the 62 kDa active MMP-2. The present study investigated if H-Ras and/or N-Ras induces pro-MMP-2 activation of MCF10A cells when cultured in two-dimensional gel of type I collagen. Type I collagen induced activation of pro-MMP-2 only in H-Ras MCF10A cells but not in N-Ras MCF10A cells. Induction of active MMP-2 by type I collagen was suppressed by blocking integrin ${\alpha}2$, indicating the involvement of integrin signaling in pro-MMP-2 activation. Membrane-type (MT)1-MMP and tissue inhibitor of metalloproteinase (TIMP)-2 were up-regulated by H-Ras but not by N-Ras in the type I collagen-coated gel, suggesting that H-Ras-specific up-regulation of MT1-MMP and TIMP-2 may lead to the activation of pro-MMP-2. Since acquisition of pro-MMP-2 activation can be associated with increased malignant progression, these results may help understanding the mechanisms for the cell surface matrix-degrading potential which will be crucial to the prognosis and therapy of breast cancer metastasis.

섬유아세포에서 프로모터 다형성에 의한 Matrix Metalloproteinase-1의 발현에 관한 연구

이진우,정유정,봉심규,박노준,이상헌,노민수,임경민,김수남,Lee, Jin Woo,Jung, Yujung,Bong, Sim-Kyu,Park, No-June,Lee, Sang Heon,Noh, Minsoo,Lim, Kyung-Min,Kim, Su-Nam 대한화장품학회 2021 대한화장품학회지 Vol.47 No.3

본 연구는 피부 섬유아세포에 자외선을 조사하거나 TNF-α를 처리하면 세포에 따라 MMP-1의 발현이 다르게 나타나는데, 이것이 MMP-1 프로모터의 다형성에 의해서 나타남을 밝히기 위해 수행되었다. 시판하는 23 종의 primary 섬유아세포에 대하여 MMP-1 프로모터의 -1607 부위의 유전형을 분석한 결과 6 개의 1G/1G 유전형, 10 개의 1G/2G 유전형, 7 개의 2G/2G 유전형을 가진 섬유아세포를 확인할 수 있었다. Hs68과 Detroit 551 세포주는 1G/2G 유전형을 가지는 것으로 확인되었다. 1G/1G 유전형은 TNF-α 처리에 의해 대조군에 비해 MMP-1이 2 배 높게 발현되었으며, 자외선에 의해서는 거의 발현되지 않았다. 1G/2G 유전형의 경우는 TNF-α 처리에 의해 MMP-1이 2.45 배 높게 발현되었으며, 자외선에 의해서는 1.4 배 MMP-1이 발현되었다. 2G/2G 유전형의 경우는 TNF-α 처리에 의해 MMP-1이 1.35 배 발현되었으며, 자외선에 의해서는 2.5 배로 높게 발현되었다. 즉 1G 유전형은 TNF-α에 의해, 2G 유전형은 자외선에 의해 발현이 유도되는 것으로 추정할 수 있으며, -1607 위치에 하나 더 삽입된 G에 의해서 Ets 전사인자가 결합할 수 있는 site가 만들어져서 MMP-1의 발현이 증가한다고 추정할 수 있으며, 피부 노화와 관련하여 섬유아세포에서는 이에 대한 연구가 전혀 진행되어 있지 않아서 향후 추가로 연구되어야 할 부분이다. 피부는 내인성 노화와 광노화의 영향을 동시에 받는 기관이므로, 피부 노화를 개선하기 위한 타겟으로 MMP-1의 발현을 분석할 경우에는 실험 조건에 적합한 유전형을 가지는 세포를 선택하여 연구를 진행하는 전략을 세워야 할 필요성이 대두된다. The skin fibroblasts of different origins showed different expression levels of MMP-1 in response to TNF-α treatment or UV irradiation. We hypothesized that this is caused by polymorphism in the MMP-1 promoter region. To elucidate it, first of all, we analyzed and classified the genotype of the -1607 site of the MMP-1 promoter in 23 commercially available primary fibroblasts, and then we examined the expression of MMP-1 by TNF-α or UVB stimulation for each classified genotype. As a result of the analysis, fibroblasts with 6 1G/1G genotypes, 10 1G/2G genotypes, and 7 2G/2G genotypes were identified. Hs68 and Detroit 551 cell lines were confirmed to have 1G/2G genotypes. In the 1G/1G genotype, MMP-1 was expressed twice as high as that of the control group by TNF-α treatment, and was hardly expressed by UV light. In the case of the 1G/2G genotype, MMP-1 was expressed 2.45 fold higher by TNF-α treatment, and 1.4 fold by UV light than the control. In the case of the 2G/2G genotype, MMP-1 was expressed 1.35 fold by TNF-α treatment, and was highly expressed by 2.5 fold by ultraviolet rays compared to control. It can be estimated that MMP-1 expression is better induced in the 1G genotype by TNF-α and in the 2G genotype by UV light. In addition, it can be presumed that MMP-1 expression is increased by creating a site where the Ets transcription factor can bind by another G inserted at the -1607 position. These studies have not been conducted at all in fibroblasts in relation to skin aging, so it is an area that needs to be further studied in the future. In conclusion, since the skin is an organ that is affected by both intrinsic aging and photoaging at the same time, when analyzing the expression of MMP-1 as a target for improving skin aging, it is necessary to select cells with a genotype suitable for the experimental conditions of the study.

간세포 성장인자가 HT 세포주에서 matrix metalloproteinase 의 발현에 미치는 영향

신종철(Jong Chul Shin),문희봉(Hee Bong Moon),이지현(Jee Hyun Lee),양동은(Dong Eun Yang),이귀세라(Gui Se Ra Lee),이영(Young Lee),이종승(Jong Seong Lee),김창이(Chang Yi Kim),김수평(Soo Pyung Kim) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.12

Objective : This study was performed to investigate the influence of hepatocyte growth factor (HGF) on matrix metalloproteinase (MMP), which are related in the lysis process of tissue during the invasion of trophoblasts. Method : HT cell line was treated with recombinant HGF (rHGF) of different concentration (0, 10, 50 and 100 ng/mL) and was cultured for 24 hours to check the changes in the expression of MMP-2 and MMP-9. Also, HT cell line was treated with recombinant HGF 50 ng/mL and was cultured for 24, 36, 48, and 72 hours to check the changes in the expression of MMPs according to the different time span. Total RNA were extracted from each cultured sample and RT-PCR and Western blotting were used to analyze the expression of MMP-2 and MMP-9. Results : MMP-2 mRNA expression with treated rHGF showed increase of 2, 2.5 and 2.2 times with the increase of concentration level of 10, 50 and 100 ng/mL accordingly, while MMP-2 protein expression were increased 1.4 and 1.5 times in 50 ng/mL and 100 ng/mL of rHGF respectively compared with that of normal control. MMP-9 mRNA showed no significant changes in its expression with all different levels of concentration, while MMP-9 protein showed 1.5 times increase with 10 ng/mL rHGF but 0.4 times decrease with 100 ng/mL. MMP-2 mRNA expression treated with recombinat HGF were increased 1.6 times with 24 hour culture and 2.3 times with 36 hour culture. MMP-2 protein showed 1.9 times increase only for the case of 24 hour culture. MMP-9 mRNA expression of recombinant HGF-treated groups was decreased 0.7 times compared with that of control group in 36 hours. MMP-9 protein expression were increased by 1.2, 1.6 and 1.9 times as culture time increase to 36, 48, and 72 hours accordingly, compared with that of normal control. Conclusion : This result suggests that the HGF might partially regulate the invasion of trophoblasts through MMP-2 and MMP-9.

비소세포 폐암에서 COX-2, MMP-9, p53 및 VEGF 발현에 대한 면역조직화학적 연구 : 편평세포암종과 선암종을 대상으로

하경원 외 중앙대학교 의과대학 의학연구소 2007 中央醫大誌 Vol.32 No.3

Purpose: This study was performed to investigate immunohistochemical expression of COX-2, MMP-9 and p53 using surgical specimens of 97 non-small-cell lung cancer cases and to evaluate the relationship between the expression of each molecule and clinicopathologic factors or prognosis. Methods: The following formalin-fixed paraffin embedded surgical specimens were immunohistochemically stained by avidin-biotin complex method for COX-2, MMP-9 and p53; 60 cases of primary squamous cell carcinoma and 37 cases of primary adenocarcinoma of the lung. Results: COX-2 expression of adenocarcinoma is statistically higher than that of squamous cell carcinoma (p<0.01). However, MMP-9, p53 and VEGF expression is not significantly associated with the histologic type of cancer. COX-2 expression was significantly associated with the clinical staging (p<0.05), whereas MMP-9, p53 and VEGF expression were not. Synchronous expression of each molecules (COX-2 + MMP-9 + p53 + VEGF, COX-2 + MMP-9 +p53, COX-2 + MMP-9 + VEGF, COX-2 + p53 + VEGF, COX-2 + MMP-9, COX-2 + p53, MMP-9 + p53, COX-2 + VEGF, MMP-9 + VEGF, p53 + VEGF) was 62.4% in frequency and revealed increased tendency in advanced cancer than early cancer. VEGF expression showed to portend a short survival among patients with non-small cell lung cancer (p=0.05). Conclusion: These results suggested that COX-2 overexpression might be an indicator of an unfavorable clinical outcome and VEGF overexpression appears to portend a short survival. However, further studies of a possibility of prognostic significance, such as MMP-9, p53 and synchronous production of gene products, are required for the determination of significant relationship in other clinicopathologic indices.

비소세포폐암에서 COX-2, MMP-9와 돌연변이형p53의 발현이 생존에 대한 예후 분석

신종욱 ( Jong Wook Shin ),최재호 ( Jae Ho Choi ),박인원 ( In Won Park ),유재형 ( Jae Hyung Yoo ) 대한결핵 및 호흡기학회 2007 Tuberculosis and Respiratory Diseases Vol.63 No.1

연구배경: 폐암의 병인에 기여하거나 예후를 결정하는 인자에 대해서는 매우 다양한 인자와 다양한 상호 관계로 인하여 특히 유전자의 역할에 대해서는 결정적으로 알려진 것이 없어 앞으로 더 많은 연구가 필요한 실정이다. 이에 따라 본 연구에서는 COX-2, MMP-9, p53가 비소세포폐암에서 어떻게 발현되는지 세포면역학적으로 알아보고 임상 특성과 예후와 상관관계를 알아보고자 하였다. 대상 및 방법: 91명의 비소세포폐암을 대상으로 하여 후향적으로 임상특성을 고찰하고 COX-2, MMP- 9, p53의 유전자 표현을 세포면역학적 방법을 통하여 검사하였다. 임상특성과 유전자 표현 패턴의 상관관계와 생존에 대한 예후인자로서의 역할에 대하여 조사하였다. 결과: 1) 편평상피세포암에서는 흡연자과 남자가 우세한 비율을 차지하였으며 남자에서 흡연의 비율이 유의하게 높았다. 2) 전체 대상 환자에서 생존에 영향을 미치는 결정적인 인자는 근치적 절제술의 시행여부와 병기로 나타났다. 3) COX-2의 발현은 편평상피세포암 보다 선암에서 더 유의하게 높게 발현되었다. 4) COX-2, MMP-9, p53의 발현이 모두 되지 않는 비율은 선암에 비해 편평상피세포암에서 더 흔하게 관찰되었다. 5) p53돌연변이가 있으면서 COX-2와 MMP-9은 발현이 되지 않는 비소세포폐암환자의 생존기간이 다른 발현 양상을 보이는 경우에서의 생존기간보다 더 연장되어 보였다(생존기간의 중앙값; 165.6주). 6) COX-2의 발현과 MMP-9의 발현 사이에는 유의한 상관관계가 있었다. 7) 폐암을 근치적으로 절제한 환자의 경우에 COX-2의 발현은 유의한 예후인자였다. MMP-9는 근치적 절제술을 받지 못한 환자군에서 유의한 예후인자로 작용하였다. 결론: COX-2와 MMP-9의 발현은 비소세포폐암 환자 일부에서 병의 진행에 관여하거나 예후에 영향을 줄 수 있을 것으로 기대된다. Background: In pathogenesis and prognosis of lung cancer, significance of enormous types of genetic expression were very compounding and undetermined. We performed this study to search association between clinical characteristics and expression of COX-2, MMP-9 and p53 in non-small cell lung cancer. Methods: Ninety-one patients with adenocarcinoma or squamous cell carcinoma were enrolled. We had searched clinical data retrospectively and performed immunohistochemical staining for COX-2, MMP-9 and p53. We had analyzed significance of these three genes in clinical features and prognosis for survival. Results: 1) In squamous cell carcinoma, male was predominant and was significantly correlated with smoking. 2) Major prognostic determinants for overall survival were curative resection. 3) Expression of COX-2 was more frequent in adenocarcinoma than in squamous cell carcinoma. 4) Negative staining of COX-2, MMP-9 and p53 was more frequent in squamous cell carcinoma than adenocarcinoma. 5) Survival duration was longer in the group with positive expression of p53 and negative for COX-2 and MMP-9 (median duration of survival = 165.6 weeks) than groups with the other expressional patterns. 6) Significant correlation was found between expression of MMP-9 and COX-2. In squamous cell carcinoma, expression of MMP-9, COX-2 and mutant p53 were mutually correlated. 7) COX-2 expression was significant prognostic factor for survival in resected cancer group. In unresected inoperable non-small cell lung cancer group, MMP-9 was statistically significant prognostic factor for overall survival. Conclusion: COX-2 and MMP-9 might have some roles for progression or prognosis in some selected patients with non-small cell lung cancer. COX-2 and MMP-9 may have some roles for disease progression or prognosis in selected patients with NSCLC. (Tuberc Respir Dis 2007; 63: 31-41)

만성 간질환에서 혈중 Gelatinase (Matrix Metalloproteinase-2와 9)의 측정 의의

권오상,임도윤,권광안,정문기,박동균,김선숙,김연석,권소영,구양서,김유경,최덕주,김주현,황유진,변관수,이창홍 대한간학회 2003 Clinical and Molecular Hepatology(대한간학회지) Vol.9 No.3

목적: Gelatinase (MMP-2와 9)는 기저막의 주구성요인 type IV collagen을 분해하는 효소로, MMP-2는 간경변과 MMP-0은 간세포암의 진행과 연관이 있는 것으로 알려져 있다. 본 연구에서는 만성 간질환과 MMP-2와 9의 관계를 알아보고자 하였다. 대상과 방법: 간기능이 정상이고 간질환이 없는 건강 대조군 10예, 만성 간염 15예, 간경변 18예, 그리고 간세포암 25예를 대상으로 혈장을 채취하여 MMP-2와 9의 활성을 보기 위해 zymography를 시행하였다. 결과: 혈장 MMP-2의 활성은 간경변군에서 건강 대조군(p=0.009)과 만성 간염군(p=0.011)에 비해 증가되어 있었으나 간세포암군과는 차이가 없었다. 혈장 MMP-9의 활성은 간경변군에서 건강 대조군에 비해 증가되어 있었으나(p=0.035), 만성 간염군과 간세포암군과는 차이가 없었다. 간세포함이 없는 간경변군 15예와 간세포암을 동반한 간경변군 23예를 합친 총 간경변군 38예에서 MMP-2의 활성은 total bilirubin이 높을수록 (r=0.323, p=0.048) 그리고 Child-Pugh 점수가 높을수록(r=0.414, p=0.012) 증가되어 있었다. 총 간경변군에서 MMP-2와 MMP-9의 활성은 알코올 성 간경변군에서 HBV에 의한 간경변군 보다 현저히 증가되어 있었다(각각 p=0.009, p=0.002). 결론: 혈장 MMP-2의 활성은 간경변의 진단과 중증도에 유용한 표지자로 사용될 수 있을 것이다. 혈장 MMP-9의 활성은 간세포암에서의 유용성은 적으리라 생각되나 알코올성 간경변의 진단적 표지자로는 유용하리라 생각된다. MMP-2와 MMP-9의 활성은 간경변의 원인 별로 차이가 나는 것으로 생각되며 그 이유에 대한 연구가 필요하리라 생각된다. Background/Aims: Gelatinase (matrix metalloproteinase (MMP) -2 and 9) has an important role in the pathogenesis of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). In this study, we evaluated the relationship of gelatinase to chronic liver disease. Methods: Four groups of subjects were examined; healthy control (10 cases), chronic hepatitis (18 cases), LC (15 cases), and HCC (28 cases). The plasma of each subject was obtained, and the equal quantification of plasma protein was done. The plasma activities of MMP-2 and 9 were measured by zymography. Results: The activities of plasma MMP-2 in patients with LC were significantly higher than those in controls (p=0.009) and in patients with chronic hepatitis (p=0.011), but not different from those in patients with HCC. The activities of plasma MMP-9 in patients with LC were significantly higher than those in controls, but not different from those in patients with chronic hepatitis or HCC. In patients with LC (regardless of having HCC), the activities of MMP-2 correlated with total bilirubin (r=0.323, p=0.048) and Child-Pugh score (r=0.414, p=0.012). The activities of MMP-2 and 0 were higher in patients with LC (regardless of having HCC) caused by alcohol than caused by HBV (p=0.009 and 0.0002 for each one). Conclusions: The plasma activity of MMP-2 may be a useful marker for the diagnosis and determination of the severity of LC. The plasma activity of MMP-9 was not useful for HCC, but may be a marker for alcoholic LC. Further study is needed to determine why the plasma activity of gelatinase was higher in patients with LC caused by alcohol than by HBV.(Korean J Hepatol 2003;9:222-230)

뇌허혈 손상시 아그마틴이 기질분해효소의 발현에 미치는 영향

김재환(Jae Hwan Kim),이용우(Yong Woo Lee),김재영(Jae Young Kim),이원택(Won Taek Lee),박경아(Kyung Ah Park),이종은(Jong Eun Lee) 대한해부학회 2008 Anatomy & Cell Biology Vol.41 No.1

아그마틴은 알기닌 탈탄산효소에 의해 알기닌으로부터 생성되는 일차아민으로 포유류의 뇌에 존재함이 밝혀졌다. 최근 여러연구자에 의해 아그마틴은 일산화질소 생성효소(NOS)의 발현과 활성을 조절해 일산화질소의 생성을 조절하는 것으로 보고되었으며, 중추신경계 손상시 신경보호작용이 있는 것으로 확인되었다. 본 연구에서는 대표적인 중추신경계 손상인 뇌허혈 손상시 아그마틴이 재관류 손상시발현되는 세포외 기질분해효소인 MMP2와 MMP9의 발현에 미치는 영향을 알아보고자 하였다. 뇌허혈 손상을 2시간동안 일으킨 후 재관류와 동시에 아그마틴을 100 mg/kg의 농도로 복강 내에 투여하였다. 재관류 22시간 후에 동물을 희생하여 그 결과를 확인하였다. 아그마틴은 뇌허혈-재관류 손상시 발현되는 MMP2와 MMP9의 발현을 감소시켰다. 이러한 현상은 손상핵심부위인 대뇌피질, 선조부위뿐만 아니라 손상주변부위에서도 확인할 수 있었다. 특히 혈관부위 에서도 MMP2와 MMP9의 발현의 감소를 확인하였다. 아그마틴의 발현정도를 알아보기 위한 형광면역염색에서도 대뇌피질부위는 크게 차이가 나지 않지만 선조와 손상주변 부위는 아그마틴 처리군에서 아그마틴의 발현이 증가됨을 확인하였고, 역시 혈관부위에서 아그마틴이 상대적으로 강하게 발현됨을 알 수 있었다. 아그마틴은 여러 일산화질소 생성효소 (NOS) 중에서 nNOS와 iNOS의 발현은 줄이고, eNOS의 발현은 줄이는 것으로 보고 되었으며, MMP2와 MMP9은 nNOS와 iNOS에 의해 생성되는 일산화질소에 의해 발현이 증가되는 한편 eNOS에 의해 생성되는 일산화질소에 의해서는 그 발현이 감소하는 것으로 보고되었다. 이상의 보고들을 볼 때 아그마틴은 뇌허혈 손상시 nNOS와 iNOS를 통한 일산화질소의 생성을 감소시켜 MMP2와 MMP9의 발현을 줄이며, eNOS를 통한 일산화질소의 생성을 증가시켜 MMP2와 MMP9의 발현을 감소시키는 것으로 생각된다. Agmatine is a primary amine formed by decarboxylation of L-arginine synthesized in the mammalian brain. Recent studies have shown that agmatine is neuroprotective in models of trauma and ischemia. The purpose of this study was to evaluate the effect of agmatine on the expression of MMP2 and MMP9, which are expressed in reperfusion injury following cerebral ischemia. Mice were subjected to 2 h middle cerebral artery occlusion and 22 h reperfusion. Agmatine (100 mg/kg) was administered intraperitoneally at the start of reperfusion. Agmatine treatment significantly reduced the immunoreactivity of MMP2 and MMP9 in the cortex, striatum, and penumbra on the ipsilateral side. The immunoreactivity of MMP2 and MMP9 was markedly lower in blood vessels of the agmatine-treated group than in the experimental control group. Immunoblot analysis showed that agmatine treatment decreased the expression of MMP2 and MMP9. After exogenous agmatine administration, the expression of agmatine was higher in the striatum and penumbra of the agmatine-treated group than in the experimental control group. The fluorescence intensity was markedly greater in blood vessels in the agmatine-treated group than in the experimental control group. These data suggest that agmatine might decrease the expression of MMP2 and MMP9 by regulating NOS activity, and thereby modulating NO synthesis.