• 제목/요약/키워드: mitochondria

검색결과 1,648건 처리시간 0.024초

후코이단/이고들빼기 혼합물에 의한 HepG2 간암세포의 apoptosis 유도 (Induction of apoptosis using the mixture of fucoidan and Crepidiastrum denticulatum extract in HepG2 liver cancer cells)

  • 박세은;최다빈;오교녀;김한중;박형범;김기만
    • 한국식품저장유통학회지
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    • 제31권2호
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    • pp.276-286
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    • 2024
  • 본 연구에서는 후코이단/이고들빼기 혼합물이 HepG2 세포의 apoptosis에 미치는 영향을 확인하고 어떠한 경로를 통해 나타나는지를 조사하였다. 후코이단/이고들빼기 혼합물이 HepG2 세포의 증식을 억제하고 세포 독성을 나타냈다. 이러한 HepG2 세포의 증식 억제 및 세포 독성이 apoptosis에 의한 효과인지를 확인한 결과, DNA fragmentation과 mitochondria membrane potential의 저해를 일으키는 것을 확인하였다. 이러한 결과를 바탕으로 HepG2 세포에서 후코이단/이고들빼기 혼합물이 apoptosis를 유도하는 기전에 관여하는 단백질의 발현 양상을 확인한 결과, intrinsic apoptosis 경로인 p53을 증가시키고, Bcl-2 family인 Bcl-2의 억제 및 BAX의 증가를 통해서 cytochrome c를 증가시켜 caspase-9 활성화하였고, caspase-3를 활성화시켜 결과적으로 apoptosis를 유도하였다. 또한, 전반적으로 후코이단/이고들빼기 혼합물의 apoptosis 유도 효과는 후코이단만 처리한 것보다 더 높은 효과를 나타냈으며, 이는 이고들빼기 추출물과의 혼합물 제조를 통해서 후코이단의 apoptosis 유도 효과가 증대되는 것으로 판단된다. 이러한 결과는 후코이단/이고들빼기 혼합물이 HepG2 세포에서 apoptosis 관련 유전자의 발현 조절에 의해 항암 효과를 나타내며, 이는 후코이단/이고들빼기 혼합물의 항암 작용의 기전을 해석하였을 뿐만 아니라, 이러한 기전 연구를 바탕으로 실질적인 간암 치료제로서의 사용 가능성을 확인하기 위해서는 유용 물질 분석 및 in vivo에서 추가 실험 등이 다양하게 수행되어야 할 것으로 판단된다.

Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-Mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress

  • Hyun Hwangbo;Cheol Park;EunJin Bang;Hyuk Soon Kim;Sung-Jin Bae;Eunjeong Kim;Youngmi Jung;Sun-Hee Leem;Young Rok Seo;Su Hyun Hong;Gi-Young Kim;Jin Won Hyun;Yung Hyun Choi
    • Biomolecules & Therapeutics
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    • 제32권3호
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    • pp.349-360
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    • 2024
  • Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type of iridoid glycoside contained in Cornus officinalis, is reported to have advantages as a natural compound that prevents various diseases. However, the question of whether this phytochemical exerts any inhibitory effect against oxidative stress in muscle cells has not been well reported. Therefore, the current study aimed to evaluate whether morroniside can protect against oxidative damage induced by hydrogen peroxide (H2O2) in murine C2C12 myoblasts. Our results demonstrate that morroniside pretreatment was able to inhibit cytotoxicity while suppressing H2O2-induced DNA damage and apoptosis. Morroniside also significantly improved the antioxidant capacity in H2O2-challenged C2C12 cells by blocking the production of cellular reactive oxygen species and mitochondrial superoxide and increasing glutathione production. In addition, H2O2-induced mitochondrial damage and endoplasmic reticulum (ER) stress were effectively attenuated by morroniside pretreatment, inhibiting cytoplasmic leakage of cytochrome c and expression of ER stress-related proteins. Furthermore, morroniside neutralized H2O2-mediated calcium (Ca2+) overload in mitochondria and mitigated the expression of calpains, cytosolic Ca2+-dependent proteases. Collectively, these findings demonstrate that morroniside protected against mitochondrial impairment and Ca2+-mediated ER stress by minimizing oxidative stress, thereby inhibiting H2O2-induced cytotoxicity in C2C12 myoblasts.

Driver의 개념변화 학습 모형을 적용한 수업이 고등학생들의 식물의 광합성과 호흡의 오개념 교정에 미치는 효과 (Effects of Teaching Based on Driver's Conceptual Change Model on Rectifying High School Students' Misconception of Photosynthesis and Respiration)

  • 김동렬
    • 한국과학교육학회지
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    • 제29권6호
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    • pp.712-729
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    • 2009
  • 본 연구에서는 고등학생들의 식물의 광합성과 호흡에 관련된 오개념을 조사하고, 이를 교정할 수 있는 방안으로 Driver 개념변화 학습 모형을 적용한 수업 프로그램을 개발 적용하여 그 효과를 알아보는데 목적이 있다. 연구 대상은 부산광역시 소재의 남자고등학교 재량교과 시간에 생물학습을 선택한 1학년 66명을 연구 대상으로 하였으며, 학생들의 광합성과 식물의 호흡에 관한 개념 정도는 그림그리기와 서술형 검사로 서로 상호적인 방법으로 조사되었다. 광합성과 식물 호흡에 관한 학생의 오개념을 단계별 수준으로 구분 짓는 방법으로 그림그리기 방법을 적용한 결과, 많은 학생들이 과학교과서나 과학자에 의해 이해되지 않은 오개념이 포함된 그림을 그렸으며, Driver 개념 변화 학습 모형 적용 후에는 식물의 광합성과 호흡의 필수 요소인 빛, 이산화탄소, 물, 포도당, 산소, 나뭇잎, 엽록체, 미토콘드리아, 기공, 에너지 등을 포함한 과학적 인 그림을 그렸다. 식물의 광합성과 호흡의 여러 측면에 대한 개념을 조사하기 위해 실시한 서술형 검사 결과에도 사전검사에서는 식물의 광합성과 호흡이 일어나는 시점과 장소, 식물의 영양소, 광합성에서의 잎의 역할, 식물의 광합성과 호흡의 관계에 대해서 많은 학생들이 오개념을 보였으나, Driver 개념변화 학습 모형을 적용한 수업 후에는 식물의 광합성과 호흡에 대한 오개념이 많이 교정된 것으로 나타났다.

Vitamin D Attenuates Pain and Cartilage Destruction in OA Animals via Enhancing Autophagic Flux and Attenuating Inflammatory Cell Death

  • JooYeon Jhun;Jin Seok Woo;Ji Ye Kwon;Hyun Sik Na;Keun-Hyung Cho;Seon Ae Kim;Seok Jung Kim;Su-Jin Moon;Sung-Hwan Park;Mi-La Cho
    • IMMUNE NETWORK
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    • 제22권4호
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    • pp.34.1-34.19
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    • 2022
  • Osteoarthritis (OA) is the most common form of arthritis associated with ageing. Vitamin D has diverse biological effect on bone and cartilage, and observational studies have suggested it potential benefit in OA progression and inflammation process. However, the effect of vitamin D on OA is still contradictory. Here, we investigated the therapeutic potential of vitamin D in OA. Six-week-old male Wistar rats were injected with monosodium iodoacetate (MIA) to induce OA. Pain severity, cartilage destruction, and inflammation were measured in MIA-induced OA rats. Autophagy activity and mitochondrial function were also measured. Vitamin-D (1,25(OH)2D3) and celecoxib were used to treat MIA-induced OA rats and OA chondrocytes. Oral supplementation of vitamin D resulted in significant attenuations in OA pain, inflammation, and cartilage destruction. Interestingly, the expressions of MMP-13, IL-1β, and MCP-1 in synovial tissues were remarkably attenuated by vitamin D treatment, suggesting its potential to attenuate synovitis in OA. Vitamin D treatment in OA chondrocytes resulted in autophagy induction in human OA chondrocytes and increased expression of TFEB, but not LC3B, caspase-1 and -3, in inflamed synovium. Vitamin D and celecoxib showed a synergistic effect on antinociceptive and chondroprotective properties in vivo. Vitamin D showed the chondroprotective and antinociceptive property in OA rats. Autophagy induction by vitamin D treatment may be a promising treatment strategy in OA patients especially presenting vitamin D deficiency. Autophagy promoting strategy may attenuate OA progression through protecting cells from damage and inflammatory cell death.

Synergistic Effect of Hydrogen and 5-Aza on Myogenic Differentiation through the p38 MAPK Signaling Pathway in Adipose-Derived Mesenchymal Stem Cells

  • Wenyong Fei;Erkai Pang;Lei Hou;Jihang Dai;Mingsheng Liu;Xuanqi Wang;Bin Xie;Jingcheng Wang
    • International Journal of Stem Cells
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    • 제16권1호
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    • pp.78-92
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    • 2023
  • Background and Objectives: This study aims to clarify the systems underlying regulation and regulatory roles of hydrogen combined with 5-Aza in the myogenic differentiation of adipose mesenchymal stem cells (ADSCs). Methods and Results: In this study, ADSCs acted as an in vitro myogenic differentiating mode. First, the Alamar blue Staining and mitochondrial tracer technique were used to verify whether hydrogen combined with 5-Aza could promote cell proliferation. In addition, this study assessed myogenic differentiating markers (e.g., Myogenin, Mhc and Myod protein expressions) based on the Western blotting assay, analysis on cellular morphological characteristics (e.g., Myotube number, length, diameter and maturation index), RT-PCR (Myod, Myogenin and Mhc mRNA expression) and Immunofluorescence analysis (Desmin, Myosin and 𝛽-actin protein expression). Finally, to verify the mechanism of myogenic differentiation of hydrogen-bound 5-Aza, we performed bioinformatics analysis and Western blot to detect the expression of p-P38 protein. Hydrogen combined with 5-Aza significantly enhanced the proliferation and myogenic differentiation of ADSCs in vitro by increasing the number of single-cell mitochondria and upregulating the expression of myogenic biomarkers such as Myod, Mhc and myotube formation. The expressions of p-P38 was up-regulated by hydrogen combined with 5-Aza. The differentiating ability was suppressed when the cells were cultivated in combination with SB203580 (p38 MAPK signal pathway inhibitor). Conclusions: Hydrogen alleviates the cytotoxicity of 5-Aza and synergistically promotes the myogenic differentiation capacity of adipose stem cells via the p38 MAPK pathway. Thus, the mentioned results present insights into myogenic differentiation and are likely to generate one potential alternative strategy for skeletal muscle related diseases.

Integrative analysis of microRNA-mediated mitochondrial dysfunction in hippocampal neural progenitor cell death in relation with Alzheimer's disease

  • A Reum Han;Tae Kwon Moon;Im Kyeung Kang;Dae Bong Yu;Yechan Kim;Cheolhwan Byon;Sujeong Park;Hae Lin Kim;Kyoung Jin Lee;Heuiran Lee;Ha-Na Woo;Seong Who Kim
    • BMB Reports
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    • 제57권6호
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    • pp.281-286
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    • 2024
  • Adult hippocampal neurogenesis plays a pivotal role in maintaining cognitive brain function. However, this process diminishes with age, particularly in patients with neurodegenerative disorders. While small, non-coding microRNAs (miRNAs) are crucial for hippocampal neural stem (HCN) cell maintenance, their involvement in neurodegenerative disorders remains unclear. This study aimed to elucidate the mechanisms through which miRNAs regulate HCN cell death and their potential involvement in neurodegenerative disorders. We performed a comprehensive microarray-based analysis to investigate changes in miRNA expression in insulin-deprived HCN cells as an in vitro model for cognitive impairment. miR-150-3p, miR-323-5p, and miR-370-3p, which increased significantly over time following insulin withdrawal, induced pronounced mitochondrial fission and dysfunction, ultimately leading to HCN cell death. These miRNAs collectively targeted the mitochondrial fusion protein OPA1, with miR-150-3p also targeting MFN2. Data-driven analyses of the hippocampi and brains of human subjects revealed significant reductions in OPA1 and MFN2 in patients with Alzheimer's disease (AD). Our results indicate that miR-150-3p, miR-323-5p, and miR-370-3p contribute to deficits in hippocampal neurogenesis by modulating mitochondrial dynamics. Our findings provide novel insight into the intricate connections between miRNA and mitochondrial dynamics, shedding light on their potential involvement in conditions characterized by deficits in hippocampal neurogenesis, such as AD.

식품원료로 사용금지 대상인 기름치 (기름갈치꼬치 및 흑갈치꼬치) 판별법 개발 (Development of Detection Method for Oilfish (Ruvettus pretiosus and Lepidocybirium flavobrunneum) as a Food Materials not Usable in Foods)

  • 박용춘;김미라;정용현;신준호;김규헌;이재황;조태용;이화정;이상재;한상배
    • 한국식품위생안전성학회지
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    • 제28권1호
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    • pp.50-55
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    • 2013
  • 기름치를 참치회 또는 메로구이로 판매하는 사례가 있으며 국내에서는 2012년 6월1일부터 식품원료로 판매가 금지되어 이를 판별하는 시험법 마련이 필요하다. 기름치는 농어목(Perciformes) 갈치꼬치과(Gempylidae)에 속하는 기름갈치꼬치(R. pretiosus)와 흑갈치꼬치(L. flavobrunneum)가 있으며 이를 판별하기 위한 종 특이 프라이머를 개발하기 위하여 미토콘드리아에 존재하는 16S DNA 유전자부위를 선정하였다. 그리고 미국 국립보건원에서 운영하는 유전자 은행(www.ncbi.nlm.nih.gov)에 등록되어있는 기름갈치꼬치, 흑갈치꼬치. 참다랑어, 황다랑, 청새치 및 황새치의 염기서열을 대상으로 BioEdit ver. 7.0.9.0 프로그램을 사용하여 비교 및 분석을 실시하였다. 분석을 통하여 기름갈치꼬치 및 흑갈치꼬치를 판별할 수 있는 각각 4종의 프라이머를 설계하였다. 설계된 프라이머에 대하여 대조군으로 다랑어 3종(참다랑어, 황다랑어, 눈다랑어) 및 새치류 4종(청새치, 황새치, 녹새치, 돛새치)에 대한 실험적 평가를 실시하였다. 그 결과 기름갈치꼬치에 대하여는 R.P-16S-006-F/R.P-16S-008-R, 흑갈치꼬치는 L.F-16S-004-F/L.F-16S-006-R 프라이머를 최종 선정하였으며, PCR 조건을 확립하였다. 확립된 조건에서는 각각 178bp 및 238bp의 PCR 산물을 확인하였으며, 유사종간의 비특이적 밴드는 형성되지 않았다. 따라서 본 연구에서 개발된 기름치를 판별할 수 있는 종 특이 프라이머는 인터넷쇼핑몰 또는 시중에 불법적으로 유통 가능성이 있는 제품을 신속하고 과학적으로 판별할 수 있어 식품안전관리에 활용도가 매우 클 것으로 기대된다.

Effects of Endocrine Disruptors (NP, DBP and BPA) on Sperm Characteristics and Development of IVF Embryos in Pig

  • Yuh, In Suh;Cheong, Hee Tae;Kim, Jong Taek;Park, In Chul;Park, Choon Keun;Yang, Boo Keun
    • Journal of Animal Science and Technology
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    • 제55권4호
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    • pp.237-247
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    • 2013
  • This study was to examine single or combined in vitro effects of environmental endocrine disruptors on boar sperm characteristics, oxidative stress damage in sperm and development of porcine IVF embryos. Addition of various concentration of NP (10, 20, $30{\mu}M$), DBP (10, 50, $100{\mu}M$) and BPA (1, 5 or $10{\mu}g/ml$) on boar sperm characteristics such as percentages of sperm motility, viability, membrane integrity and mitochondrial activity were dose-dependently decreased within 3, 6 or 9 hr incubation period (p<0.05). The overall detrimental effects increased with incubation time increasement. NP, DBP and BPA showed the detrimental effects on sperm membrane and mitochondria of energy production organelles affecting cell viability with the dependancy of dose and incubation time. In combination effects, NP ($10{\mu}M$) + DBP ($10{\mu}M$) significantly decreased boar general sperm characteristics for 3 or 6 hr incubation period compared with control (p<0.05). When both of NP and DBP concentrations (NP; $30{\mu}M$, DBP; $100{\mu}M$) increase, the detrimental effects on sperm characteristics were larger than those of low concentration combination (p<0.05). The inhibitory effects of NP ($30{\mu}M$) + BPA ($10{\mu}g/ml$) on sperm characteristics were larger than those of NP ($10{\mu}M$) + BPA ($1{\mu}g/ml$) (p<0.05). DBP ($100{\mu}M$) + BPA ($10{\mu}g/ml$) decreased sperm characteristics compared with the low concentration combination (DBP $10{\mu}M$ + BPA $1{\mu}g/ml$, p<0.05). This result indicates the detrimental effects of both chemicals on sperm characteristics were dose dependent. Addition of NP ($30{\mu}M$) + DBP ($100{\mu}M$), NP ($30{\mu}M$) + BPA ($10{\mu}g/ml$), DBP ($10{\mu}M$) + BPA ($1{\mu}g/ml$) or DBP ($100{\mu}M$) + BPA ($10{\mu}g/ml$) significantly increased lipid peroxidation for 3 or 6 hr incubation period (p<0.05) compared with no addition control. NP (${\geq}20{\mu}M$) decreased the percentages of IVF embryo development from morulae and blastocyst stages (p<0.05) and its detrimental effects were dose-dependant. BPA 0, 1, 5 or $10{\mu}g/ml$ decreased significantly and dose-dependently the percentage of morulae plus and blastocysts (p<0.05). Combinations of DBP ($100{\mu}M$) plus NP ($30{\mu}M$) and DBP ($100{\mu}M$) plus BPA ($10{\mu}g/ml$) did not affect on morulae and blastocyst development, but NP ($30{\mu}M$) plus BPA ($10{\mu}g/ml$) has significant detrimental effect on embryo development at these stages (p<0.05). These overall results indicate that the partial detrimental effects on boar sperm characteristics and embryo development by NP, DBP, BPA or the combination of these chemicals might be due to the increasement of lipid peroxidation and free radical formation in the cell and there were no specific interaction effects on boar sperm and embryo degeneration among the combined treatments.

cDNA Microarray를 이용한 구강편평세포암종 세포주에서 $Taxol^{(R)}$과 Cyclosporin A로 유도된 유전자 발현양상 (GENE EXPRESSION PATTERNS INDUCED BY $TAXOL^{(R)}$ AND CYCLOSPORIN A IN ORAL SQUAMOUS CELL CARCINOMA CELL LINE USING CDNA MICROARRAY)

  • 김용관;이재훈;김철환
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제28권3호
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    • pp.202-212
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    • 2006
  • It is well-known that paclitaxel($Taxol^{(R)}$), which is extracted from the pacific and English yew, has been used as a chemotherapeutic agent for ovarian carcinoma and advanced breast carcinoma and Cyclosporin A, which is highly lipophilic cyclic peptide and isolated from a fungus, has been also used as an useful immunosuppressive drug after transplantation and is associated with cellular apoptosis. Since 1953, in which James Watson, Rosalind Franklin and Francis Crick discovered the double helical structure of DNA, a few kinds of techniques for identifying gene expression have been developed. In postgenomic period, many of researchers have used the DNA microarray which is high throughput screening technique to screen large numbers of gene expression simultaneously. In this study, we searched and screened the gene expression in the oral squamous cell carcinoma cell lines treated with $Taxol^{(R)}$, cyclosporin or cyclosporin combined with $Taxol^{(R)}$ using cDNA microarray. The results were as following; 1. It was useful that the appropriate concentration of Cyclosporin A and $Taxol^{(R)}$ used in oral squamous cell carcinoma cell line was under 1${\mu}g/ml$ and 3${\mu}g/ml$. 2. In the experimental group in which $Taxol^{(R)}$ and $Taxol^{(R)}$ + Cyclosporin A were used, the cell growth was extremely decreased. 3. In the group in which Cyclosporin A was used, the MTT assay was rarely decreased which means the activity of succinyl dehydrogenase is remained in mitochondria but in the group in which the mixture of Cyclosporin A and $Taxol^{(R)}$ were used, the MTT assay was extremely decreased. 4. In the each group in which Cyclosporin A(3 ${\mu}g/ml$) and $Taxol^{(R)}$(1 ${\mu}g/ml$) were used, the cell arrest was appeared in $G_2/M$ phase and in the group in which $Taxol^{(R)}$(3 ${\mu}g/ml$) was used, the cell arrest was appeared in both S phase and $G_2/M$ phase. 5. In the oral squamous cell carcinoma cell line treated with $Taxol^{(R)}$, several genes including ANGPTL4, RALBP1 and TXNRD1, associated with apoptosis, SUI1, MAC30, RRAGA and CTGF, related with cell growth, HUS1 and DUSP5, related with cell cycle and proliferation, ATF4 and CEBPG, associated with transcription factor, BTG1 and VEGF, associated with angiogenesis, FDPS, FCER1G, GPA33 and EPHA4 associated with signal transduction and receptor activity and AKR1C2 and UGTA10 related with carcinogenesis were detected in increased levels. The genes that showed increaced expression in the oral squamous cell carcinoma cell line treated with Cyclosporin A were CYR61, SERPINB2, SSR3 and UPA3A which are known as genes associated with cell growth, carcinogenesis, receptor activity and transcription factor. The genes expressed in the HN22 cell line treated with cyclosporin combined with $taxol^{(R)}$ were ALCAM and GTSE1 associated with cancer invasiveness and cell cycle regulation.

유기주석화합물이 웅성생식세포주에 미치는 영향 (Mechanisms of Tributyltin-induced Leydig Cell Apoptosis)

  • Lee, Kyung-Jin;Kim, Deok-Song;Ra, Myung-Suk;Wui, Seong-Uk;Im, Wook-Bin;Park, Hueng-Sik;Lee, Jong-Bin
    • Environmental Analysis Health and Toxicology
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    • 제18권2호
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    • pp.89-94
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    • 2003
  • 본 연구는 환경 호르몬으로. 분류된 67종 중의 하나인, 선저 도료나 어망, 어구 및 방오페인트 재료로 사용되어지고 유기주석화합물(tributyltin)을 사용하여 설치류의 웅성생식세포에서 세포자연사를 일으키는 작용기작을 조사하였다 먼저 흰쥐의 레이딕 세포주인 R2C에 유기주석화합물을 농도별(1∼500 nM)로 처리한 후 DNA fragment현상을 전기영동법을 통하여 조사하였다. 그 결과 유기주석화합물을 처리한 군들에서 대조군에 비하여 세포자연사현상이 농도 의존적으로 증가하였다. 유기주석화합물이 세포 내 칼슘이온(Ca$^2$$^{+}$)및 유해 산소종(reactive oxygen species)에 미치는 영향을 조사해본 결과 유기주석화합물 처리시 세포 내 칼슘이온 및 유해 산소종이 시간에 의존적으로 크게 증가하였다. 또한 칼슘 킬레이터인 BAPTA를 전 처리한 경우 유기주석화합물에 의해 유도된 칼슘이온 및 유해 산소종이 대조군에 비해 유의성 있게 감소하였다. 이러한 세포자연사 과정이 미토콘드리아의 cytochromec방출에 의한 과정인지를 화인하기 위해 세포질 내 cytochrome c양을 western blot법을 사용하여 확인해 본 결과 유기주석화합물처리 시간 및 농도에 따라 증가하며, 이 또한 BAPTA를 전처리 한 경우 대조군에 비하여 유의성 있게 감소하였다. 또한 유기주석화합물이 세포자연사 유발 시 caspase-3 효소 활성과의 관계를 확인하기 위해 ELISA법을 사용하여 확인해 본 결과 유기주석화합물 처리 농도에 의존적으로 증가하였으며, caspase-3효소 억제자로 잘 알려진 Z-DEVD FMK을 전 처리한 경우 유기주석화합물을 처리한 군에 비해 세포자연사율이 크게 감소하였다. 이러한 결과들을 종합해 볼 때 유기주석화합물은 세포 내 칼슘이온의 증가를 일으키고, 그로 인하여 세포질 내 유해산소종 및 cytochrome c의 양이 증가함으로써 세포자연사 다음 단계인 caspase효소 활성의 증가를 통하여 흰쥐의 레이딕 세포주인 R2C의 세포자연사를 일으킬 것이라 추론할 수 있다.