• 한국식품영양과학회지
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• 제33권2호
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• pp.455-462
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• 2004

토마토에는 라이코펜과 quercetin, phytoene, phytofluene, cyclolycopene, salicylates 그리고 tomatlne과 같은 다양한 생리활성 물질들이 함유되어 있으며, 이들은 라이코펜과 함께 항암작용에 관여하는 것으로 사료된다. 생리적 농도에서 라이코펜은 세포주기의 정지(arrest)와 세포 자가사멸을 통한 암세포의 생존률을 감소시키고, 사이클린을 조절하며, 세포간의 연락체계를 증가시키는 것으로 보고되고 있다. 라이코펜은 산화에 민감하여 매우 쉽게 산화물질을 만든다. 토마토 제품의 섭취는 혈중 phytoene, phytofluene 그리고 라이코펜 산화물질인 cyclolycopene의 농도를 유의적으로 증가시켰다. 또한 토마토나 토마토 제품을 통한 라이코펜의 섭취는 혈중 라이코펜의 농도를 최고 1.26 $\mu$M까지 증가시켰다. 다양한 암 부위 (cancer sites)를 통한 19건의 동물실험결과, 10건의 실험에서 라이코펜이 효과가 입증되었고, 7건의 실험에서는 통계적인 유의성이 밝혀지지 않았고, 2건의 전립선암 실험에서는 억제효과를 보이지 않았다. 임상실험에서 라이코펜 섭취와 토마토 제품섭취군 모두 백혈구와 전립선에서 의 DNA 산화물질을 감소시킴을 확인하였다. 라이코펜은 암화과정을 방해하는 생리활성 물질로 밝혀졌으나 phytoene, phytofluene 그리고 cyclolycopene의 역할에 관해서는 아직 밝혀져 있지 않다. 따라서 라이코펜과 토마토에 함유되어 있는 다른 식물성 화학성분들(phytochemicals) 간의 상호작용에 관해서는 좀 더 구체적이고 신뢰성 있는 연구가 필요하다.

• 생명과학회지
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• 제28권1호
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• pp.43-49
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• 2018

Chrysoeriol은 alfalfa에서 주로 발견되는, 식물계에 많이 분포하고 있는 flavone으로 전통의학에서 소화불량, 천식, 비뇨기계 이상의 치료에 사용되어 왔다. 최근의 연구에서는 항염증 효과가 있는 것으로 밝혀졌으나 항산화 효과에 대한 분석은 없었다. 본 연구에서는 chrysoeriol의 항산화 효과와 그 분자적 기전을 RAW 264.7 cell에서 세포생존율, reactive oxygen species (ROS)와 Western blot분석을 통해 알아보고자 하였다. Chrysoeriol은 lipopolysaccharide(LPS)에 의해 발생한 ROS를 세포독성없이 농도의존적으로 제거하였다. 그리고 항산화효과를 보이는 2상 효소 중 하나인 heme oxygenase (HO)-1의 발현을 강하게 유도하였고, 그와 동시에 전사인자인 Nrf2의 핵내 이동도 촉진하는 것으로 밝혀졌다. 특히, 산화스트레스에 대한 세포내 산화환원항상성 유지에 중요한 역할을 하고 있는 것으로 알려진 mitogen activated protein kinase (MAPK)와 phosphoinositide 3-kinase (PI3K)의 분석결과, chrysoeriol은 extracellular signal regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK)와 p38의 인산화를 통해 HO-1의 발현을 유도하는 것으로 나타났다. HO-1에 의한 항산화 효과를 확인하기 위하여 chrysoeriol을 전처리한 후 t-BHP에 의한 산화 스트레스에 세포를 노출시킨 결과, chrysoeriol 처리에 의해 세포사멸이 줄어드는 것을 확인하였고, HO-1의 유도제와 억제제의 처리에 따라 세포생존율 또한 조절되는 것을 확인할 수 있었다. 따라서, chrysoeriol은 HO-1의 발현을 유도하여 항산화 효과를 높이고 이것은 Nrf2/MAPK 신호전달 체계에 의한다는 것을 알 수 있었다.

• 대한한방부인과학회지
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• 제25권2호
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• pp.78-88
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• 2012

Objectives: Paeonia japonica has been widely used for gynecopathy and analgesic effects in Korean Traditional Medicine. The aim of the present study is to determine the antioxidant effect of Paeonia japonica extracts(PJE) by using mouse embryonic fibroblast cells(MEF cells). Methods: We evaluated Radical Scavenging Activity of PJE by the DPPH assay. Protective effect of the PJE on the hydrogen peroxide($H_2O_2$) induced oxidative damage of MEF cells was analyzed by the MTT assay. The Morphological changes of MEF cells induced by P. japonica, $H_2O_2$ and P. japonica+$H_2O_2$ was evaluated by DAPI staining. And effect of PJE on the rate of apoptosis in MEF cells was measured using flow cytometry with Annexin V-FITC and PI double staining. Results: We observed that PJE contain significant DPPH radical scavenging activity. Cell viability of oxidative damaged cells treated with various concentrations of $H_2O_2$ was increased by treatment with PJE. Flow cytometric analysis of the cells treated with $H_2O_2$ in the absence or presence of PJE showed that the crumbled G1 peak was accumulated by the treatment with $H_2O_2$ alone, but restored by addition of PJE. Portion of cells that undergo apoptosis mediated by oxidative stress was decreased by treatment of PJE. The nuclear fragmentation occurred in the oxidative damaged MEF cells was also decreased by PJE treatment. Conclusions: Taken together, our results suggest that PJE exhibits significant antioxidant activity and functions to inhibit cell death mediated by oxidative damage induced apoptotic pathways.

• Journal of Korean Neurosurgical Society
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• 제67권4호
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• pp.418-430
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• 2024

Objective : Isoflurane, a widely used common inhalational anesthetic agent, can induce brain toxicity. The challenge lies in protecting neurologically compromised patients from neurotoxic anesthetics. Choline alfoscerate (L-α-Glycerophosphorylcholine, α-GPC) is recognized for its neuroprotective properties against oxidative stress and inflammation, but its optimal therapeutic window and indications are still under investigation. This study explores the impact of α-GPC on human astrocytes, the most abundant cells in the brain that protect against oxidative stress, under isoflurane exposure. Methods : This study was designed to examine changes in factors related to isoflurane-induced toxicity following α-GPC administration. Primary human astrocytes were pretreated with varying doses of α-GPC (ranging from 0.1 to 10.0 µM) for 24 hours prior to 2.5% isoflurane exposure. In vitro analysis of cell morphology, water-soluble tetrazolium salt-1 assay, quantitative real-time polymerase chain reaction, proteome profiler array, and transcriptome sequencing were conducted. Results : A significant morphological damage to human astrocytes was observed in the group that had been pretreated with 10.0 mM of α-GPC and exposed to 2.5% isoflurane. A decrease in cell viability was identified in the group pretreated with 10.0 µM of α-GPC and exposed to 2.5% isoflurane compared to the group exposed only to 2.5% isoflurane. Quantitative real-time polymerase chain reaction revealed that mRNA expression of heme-oxygenase 1 and hypoxia-inducible factor-1α, which were reduced by isoflurane, was further suppressed by 10.0 µM α-GPC pretreatment. The proteome profiler array demonstrated that α-GPC pretreatment influenced a variety of factors associated with apoptosis induced by oxidative stress. Additionally, transcriptome sequencing identified pathways significantly related to changes in isoflurane-induced toxicity caused by α-GPC pretreatment. Conclusion : The findings suggest that α-GPC pretreatment could potentially enhance the vulnerability of primary human astrocytes to isoflurane-induced toxicity by diminishing the expression of antioxidant factors, potentially leading to amplified cell damage.

• Journal of Dental Anesthesia and Pain Medicine
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• 제17권1호
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• pp.21-28
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• 2017

Background: The skin consists of tightly connected keratinocytes, and prevents extensive water loss while simultaneously protecting against the entry of microbial pathogens. Excessive cellular levels of reactive oxygen species can induce cell apoptosis and also damage skin integrity. Propofol (2,6-diisopropylphenol) has antioxidant properties. In this study, we investigated how propofol influences intracellular autophagy and apoptotic cell death induced by oxidative stress in human keratinocytes. Method: The following groups were used for experimentation: control, cells were incubated under normoxia (5% $CO_2$, 21% $O_2$, and 74% $N_2$) without propofol; hydrogen peroxide ($H_2O_2$), cells were exposed to $H_2O_2$ ($300{\mu}M$) for 2 h; propofol preconditioning (PPC)/$H_2O_2$, cells pretreated with propofol ($100{\mu}M$) for 2 h were exposed to $H_2O_2$; and 3-methyladenine $(3-MA)/PPC/H_2O_2$, cells pretreated with 3-MA (1 mM) for 1 h and propofol were exposed to $H_2O_2$. Cell viability, apoptosis, and migration capability were evaluated. Relation to autophagy was detected by western blot analysis. Results: Cell viability decreased significantly in the $H_2O_2$ group compared to that in the control group and was improved by propofol preconditioning. Propofol preconditioning effectively decreased $H_2O_2$-induced cell apoptosis and increased cell migration. However, pretreatment with 3-MA inhibited the protective effect of propofol on cell apoptosis. Autophagy was activated in the $PPC/H_2O_2$ group compared to that in the $H_2O_2$ group as demonstrated by western blot analysis and autophagosome staining. Conclusion: The results suggest that propofol preconditioning induces an endogenous cellular protective effect in human keratinocytes against oxidative stress through the activation of signaling pathways related to autophagy.

• BMB Reports
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• 제49권7호
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• pp.382-387
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• 2016

Reactive oxygen species generated under oxidative stress are involved in neuronal diseases, including ischemia. Glutathione S-transferase pi (GSTpi) is a member of the GST family and is known to play important roles in cell survival. We investigated the effect of GSTpi against oxidative stress-induced hippocampal HT-22 cell death, and its effects in an animal model of ischemic injury, using a cell-permeable PEP-1-GSTpi protein. PEP-1-GSTpi was transduced into HT-22 cells and significantly protected against H2O2-treated cell death by reducing the intracellular toxicity and regulating the signal pathways, including MAPK, Akt, Bax, and Bcl-2. PEP-1-GSTpi transduced into the hippocampus in animal brains, and markedly protected against neuronal cell death in an ischemic injury animal model. These results indicate that PEP-1-GSTpi acts as a regulator or an antioxidant to protect against oxidative stress-induced cell death. Our study suggests that PEP-1-GSTpi may have potential as a therapeutic agent for the treatment of ischemia and a variety of oxidative stress-related neuronal diseases.

• The Plant Pathology Journal
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• 제24권2호
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• pp.101-111
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• 2008

The fungal genus Alternaria is comprised of many saprophytic and endophytic species, but is most well known as containing many notoriously destructive plant pathogens. There are over 4,000 Alternaria/host associations recorded in the USDA Fungal Host Index ranking the genus 10th among nearly 2,000 fungal genera based on the total number of host records. While few Alternaria species appear to have a sexual stage to their life cycles, the majority lack sexuality altogether. Many pathogenic species of Alternaria are prolific toxin producers, which facilitates their necrotrophic lifestyle. Necrotrophs must kill host cells prior to colonization, and thus these toxins are secreted to facilitate host cell death often by triggering genetically programmed apoptotic pathways or by directly causing cell damage resulting in necrosis. While many species of Alternaria produce toxins with rather broad host ranges, a closely-related group of agronomically important Alternaria species produce selective toxins with a very narrow range often to the cultivar level. Genes that code for and direct the biosynthesis of these host-specific toxins for the Alternaria alternata sensu lato lineages are often contained on small, mostly conditionally dispensable, chromosomes. Besides the role of toxins in Alternaria pathogenesis, relatively few genes and/or gene products have been identified that contribute to or are required for pathogenicity. Recently, the completion of the A. brassicicola genome sequencing project has facilitated the examination of a substantial subset of genes for their role in pathogenicity. In this review, we will highlight the role of toxins in Alternaria pathogenesis and the use of A. brassicicola as a model representative for basic virulence studies for the genus as a whole. The current status of these research efforts will be discussed.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1947-1959
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• 2016

Background: Colorectal cancer (CRC) is a major cause of morbidity and mortality, being the second most common type of cancer worldwide in both men and women. It accounts yearly for approximately 9% of all new cases of cancers. Furthermore, the current chemotherapeutic regimens seem unsatisfactory, so that exploration of novel therapeutic modalities is needed. The present study was undertaken to investigate the inhibitory effects of a crude alkaloid extract (CAERS) of a medicinal herb, Rhazya stricta, on proliferation of CRC HCT116 cells and to elucidate mechanisms of action. To achieve these aims, we utilized MTT, comet, DNA laddering and gene reporter assays, along with Western blot and RT-PCR analyses. Results: We found that CAERS inhibited cell proliferation and induced apoptotic cell death in HCT116 cells. Hallmarks of morphological and biochemical signs of apoptosis were clearly evident. CAERS down-regulated DNA-binding and transcriptional activities of NF-${\kappa}B$ and AP-1 proteins, while up-regulating expression of the Nrf-2 protein. It also down-regulated expression levels of the ERK MAPK, Bcl-2, cyclin D1, CDK-4, survivin and VEGF and up-regulated levels of Bax, caspase-3/7 and -9, p53, p21, Nrf-2. Markedly, it promoted mRNA expression levels of cytoprotective genes including the hemeoxygenase-1, NAD(P)H quinine oxidoreductase 1 and UDP-glucuronyltransferase. Conclusions: These findings indicate that CAERS exerts antiproliferative action on CRC cells through induction of apoptotic mechanisms, and suggest CAERS could be a promising agent for studying and developing novel chemotherapeutic agents aimed at novel molecular targets for the treatment of CRC.

• 동의생리병리학회지
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• 제23권6호
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• pp.1368-1378
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• 2009

Unfolded protein response (UPR) is an important genomic response to endoplasmic reticulum (ER) stress. The ER response is characterized by changes in specific proteins, induction of ER chaperones and degradation of misfolded proteins. Also, the pathogenesis of several diseases like Alzheimer's disease, neuronal degenerative diseases, and diabetes reveal the role of ER stress as one of the causative mechanisms. Borneolum has been used for neuronal disease in oriental medicine. In the present study, the protective effect of borneolum on thapsigargin-induced apoptosis in rat C6 glial cells. Treatment with C6 glial cells with 5 uM thapsigargin caused the loss of cell viability, and morphological change, which was associated with the elevation of intracellular $Ca^{++}$ level, the increase in Grp78 and CHOP and cleavage of pro-caspase 12 Furthermore, thapsigargin induced Grp98, XBP1, and ATF4 protein expression in C6 glial cells. Borneolum reduced thapsigargin-induced apoptosis through ER pathways. In the ER pathway, borneolum attenuated thapsigargin-induced elevations in Grp78, CHOP, ATF4, and XBP1 as well as reductions in pro-caspase 12 levels. Also, our data showed that borneolum protected thapsigargin-induced cytotoxicity in astrocytes from rat (P3) brain. Taken together, our data suggest that borneolum is neuroprotective against thapsigargin-induced ER stress in C6 glial cells and astrocytes. Accordingly, borneolum may be therapeutically useful for the treatment of thapsigargin-induced apoptosis in central nervous system.

• 생명과학회지
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• 제16권1호
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• pp.126-130
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• 2006

본 연구는 DNA상해유도기작을 규명하기 위하여 하등 진핵생물인 분열형 효모 Schizosaccharomyces pombe로부터 subtraction hybridization방법을 이용하여 자외선 유도 유전자인 UVI-155을 분리하고 그 유전자 구조와 발현양상을 조사하였다. UVI-155 유전자의 발현양상을 Northern hybridization 방법으로 살펴본 결과 자외선(ultraviolet-light) 조사 1시간 후에 최대의 발현 증가를 나타내었다. 반면 알킬화제 인 MMS (methyl methanesulfonate) 처리에 의해서도 발현이 증가되었다. 이 결과 다른 UV-inducible 유전자와는 다르게 UVI-l55 유전자는 UV와 MMS 등의 DNA 상해에 모두 발현이 증가됨을 알 수 있었다. 또 한 유전자의 기능을 알기 위하여 null-mutant세포 주를 제조하여 그 특성을 살펴본 결과 이 유전자는 세포의 성장에 필수적인 유전자임을 알 수 있었다.