• 대한의생명과학회지
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• 제29권3호
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• pp.201-205
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• 2023

Free adenine is mainly made during the polyamine synthesis in proliferating cells. Adenine molecule itself acts biological modulator in inflammation and cell death. In the previous report, we showed that adenine induces apoptotic cell death of B16-F10 mouse melanoma cells by eliciting of PARP and caspase 3 cleavages. In this study, we examined the adenine effect on other apoptotic molecules affecting caspase activation in B16-F10 melanoma cells. Adenine treatment make pro-apoptotic molecules active states. Bax/Bcl-2 ratio was increased and phosphorylation of mTOR and Akt was decreased in a dose dependent manner. These results showed the possibility that Bax/Bcl-2, Akt and mTOR are engaged in adenine induced apoptosis of melanoma cells.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Current Trends in Toxicological Sciences
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• pp.94-94
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• 2002

• BMB Reports
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• 제48권6호
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• pp.336-341
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• 2015

Sepsis is a life-threatening, infectious, systemic inflammatory disease. In this study, we investigated the therapeutic effect of α-cubebenoate, a novel compound isolated from Schisandra chinensis against polymicrobial sepsis in a cecal ligation and puncture (CLP) experimental model. Administration of α-cubebenoate strongly enhanced survival in the CLP model. α-cubebenoate administration also markedly blocked CLP-induced lung inflammation and increased bactericidal activity by enhancing phagocytic activity and hydrogen peroxide generation in mouse bone marrow-derived macrophages and neutrophils. Expression of two important inflammatory cytokines, IL-1 and IL-6, was strongly increased in the CLP model, and this was dramatically blocked by α-cubebenoate. Lymphocyte apoptosis and caspase-3 activation, which are associated with immune paralysis during sepsis, were markedly attenuated by α-cubebenoate. Taken together, our findings indicate that α-cubebenoate, a natural compound isolated from Schisandra chinensis, is a powerful potential anti-septic agent. [BMB Reports 2015; 48(6): 336-341]

• BMB Reports
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• 제55권10호
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• pp.500-505
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• 2022

Uncoupling protein 2 (Ucp2) was first introduced as a member of Uncoupling protein family and a regulator of ROS formation; however, its role in adipose tissue is not fully understood. In the present study, we have investigated the role of Ucp2 against high-fat diet (HFD)-induced obesity in epididymal white adipose tissue (eWAT) and browning of inguinal white adipose tissue (iWAT). Diet-induced obesity is closely related to macrophage infiltration and the secretion of pro-inflammatory cytokines. Macrophages surround adipocytes and form a crown-like-structure (CLS). Some reports have suggested that CLS formation requires adipocyte apoptosis. After 12 weeks of HFD challenge, Ucp2 knockout (KO) mice maintained relatively lean phenotypes compared to wild-type (WT) mice. In eWAT, macrophage infiltration, CLS formation, and inflammatory cytokines were reduced in HFD KO mice compared to HFD WT mice. Surprisingly, we found that apoptotic signals were also reduced in the Ucp2 KO mice. Our study suggests that Ucp2 deficiency may prevent diet-induced obesity by regulating adipocyte apoptosis. However, Ucp2 deficiency did not affect the browning capacity of iWAT.

• Nutrition Research and Practice
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• 제17권5호
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• pp.899-916
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• 2023

BACKGROUND/OBJECTIVES: Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates nerve cells. Neurodegenerative diseases are chronic central nervous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietary compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin's neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide (H₂O₂)-treated SH-SY5Y cells. MATERIALS/METHODS: SH-SY5Y cells were treated with H₂O₂ (400 µM) in hesperetin absence or presence (10-40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4',6-diamidino-2-phenylindole staining allowed us to observe nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. RESULTS: Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H₂O₂-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H₂O₂-induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NF-κB translocation into H₂O₂-treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H₂O₂-treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophagy pathways. CONCLUSION: These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietary agent that reduces neurodegenerative disease onset, progression, and prevention.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제5권1호
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• pp.1-10
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• 2002

목적: 소아기는 알코올이나 약물 등에 의한 자극이 거의 없는 시기로 H. pylori 감염의 자연 경과와 단기간의 영향을 연구하기에 적합한 시기이다. 최근 H. pylori 감염의 기전으로 중요시되고 있는 위상피세포 증식과 세포사에 대해 소아에서 알아보고자 하였다. 방법: 1996년 5월부터 2001년 6월까지 이화여자대학교 목동병원 소아과에서 소화기 증상으로 내시경을 시행하여 H. pylori 감염으로 진단된 58예와 감염 음성 40예를 대상으로 하였다. H. pylori 감염 양성은 조직학적으로 H. pylori 균이 관찰되고, CLO 검사와 ureC PCR이 전부 양성인 경우로 하였다. 위생검 조직에서 개정된 시드니 체계를 이용하여 조직 소견을 분석하고, proliferating cell nuclear antigen (PCNA) 발현으로 위 상피세포 증식의 정도를, in situ terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) 방법으로 세포사의 정도를 조사하였다. 결과: 1) H. pylori 감염 양성에서 다핵형 중성구의 활동성(P=0.000), 만성 염증(P=0.000), 상피손상(P=0.000), 림프여포(P=0.000)의 정도가 감염 음성에 비하여 유의하게 높았다. H. pylori 감염 양성에서 장형화생은 관찰되지 않았다. 2) H. pylori 감염 양성에서 세포 증식 지표는 $67.8{\pm}18.13$으로, 음성 $54.8{\pm}14.46$에 비하여 유의하게 높았다(P=0.000). 세포 증식 지표는 H. pylori 밀도가 증가할수록(r=0.277, P=0.007), 다핵형 중성구의 활동성이 증가할수 (r=0.280, P=0.007), 만성염증이 증가할수록(r=0.284, P=0.006) 증가하였다. 3) 세포사 지표는 H. pylori 감염 양성에서 $0.44{\pm}0.447$, 음성에서 $0.14{\pm}0.196$으로 감염 양성에서 음성보다 유의하게 높았다(P=0.000). 세포사 지표는 H. pylori 밀도가 증가할수록(r=0.472, P=0.000), 다핵형 중성구의 활동성이 증가할수록(r=0.370, P=0.001), 만성 염증이 증가할수록(r=0.483, P=0.000) 증가하였다. 4) 세포 증식 지표가 증가할수록 세포사 지표는 유의하게 증가하였다(r=0.353, P=0.003). 결론: H. pylori 감염 소아에서 세포 증식 지표와 세포사 지표가 유의하게 증가하였으며 상관성도 유의하였다. 이는 소아에서 위 상피세포 증식과 세포사가 H. pylori의 병인에 중요함을 시사하며, 앞으로 세포 증식과 세포사의 기전, 유발 요인 외에 다른 병독 인자와의 관련성에 대한 연구가 필요하리라 생각된다.

• BMB Reports
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• 제51권5호
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• pp.219-224
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• 2018

Necroptosis is an emerging form of programmed cell death occurring via active and well-regulated necrosis, distinct from apoptosis morphologically, and biochemically. Necroptosis is mainly unmasked when apoptosis is compromised in response to tumor necrosis factor alpha. Unlike apoptotic cells, which are cleared by macrophages or neighboring cells, necrotic cells release danger signals, triggering inflammation, and exacerbating tissue damage. Evidence increasingly suggests that programmed necrosis is not only associated with pathophysiology of disease, but also induces innate immune response to viral infection. Therefore, necroptotic cell death plays both physiological and pathological roles. Physiologically, necroptosis induce an innate immune response as well as premature assembly of viral particles in cells infected with virus that abrogates host apoptotic machinery. On the other hand, necroptosis per se is detrimental, causing various diseases such as sepsis, neurodegenerative diseases and ischemic reperfusion injury. This review discusses the signaling pathways leading to necroptosis, associated necroptotic proteins with target-specific inhibitors and diseases involved. Several studies currently focus on protective approaches to inhibiting necroptotic cell death. In cancer biology, however, anticancer drug resistance severely hampers the efficacy of chemotherapy based on apoptosis. Pharmacological switch of cell death finds therapeutic application in drug- resistant cancers. Therefore, the possible clinical role of necroptosis in cancer control will be discussed in brief.

• BMB Reports
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• 제34권5호
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• pp.463-471
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• 2001

The bark of Ulmus darvidiana var. japonica Nakai (UDN) has been used for a long time to cure inflammation in oriental medicine. In the present study, two types of extracts, Ulmus water-eluted fraction (UWF) and Ulmus ethanol-eluted fraction (UEF), were prepared from the UDN stem bark, and employed to test the extracts to see if they had anti-oxidative properties against hydroxyl radicals that could alter immune reactivity in mouse immune cells. Deoxyribose assay, DNA nicking assay, and glucose/glucose oxidase assay showed that both fractions had scavenging activity against oxygen free radicals at 50 mg/ml. In addition, hydroxyl radical-mediated apoptosis in mouse thymocytes was not protected by UEF treatment, but the apoptosis was protected by UWF at the same concentration. DNA synthesis and cytokine production that were induced in splenocytes by mitogens (Concanavalin A and lipopolysaccharide) were reduced by the addition of both fractions. These results indicate that both extracts that were prepared from the UDN stem bark have anti-oxidative activities, anti-apoptotic effects, and inhibitory effects on DNA synthesis and cytokine production in mouse immune cell cultures.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1977-1981
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• 2012

Houttuynia cordata Thunb (HCT) is a native herb found in Southeast Asia which features various pharmacological activities against allergy, inflammation, viral and bacterial infection, and cancer. The aims of this study were to determine the cytotoxic effect of 6 fractions obtained from silica gel column chromatography of alcoholic HCT extract on human leukemic Molt-4 cells and demonstrate mechanisms of cell death. Six HCT fractions were cytotoxic to human lymphoblastic leukemic Molt-4 cells in a dose-dependent manner by MTT assay, fraction 4 exerting the greatest effects. Treatment with $IC_{50}$ of HCT fraction 4 significantly induced Molt-4 apoptosis detected by annexinV-FITC/propidium iodide for externalization of phosphatidylserine to the outer layer of cell membrane. The mitochondrial transmembrane potential was reduced in HCT fraction 4-treated Molt-4 cells. Moreover, decreased expression of Bcl-xl and increased levels of Smac/Diablo, Bax and GRP78 proteins were noted on immunoblotting. In conclusion, HCT fraction 4 induces Molt-4 apoptosis cell through an endoplasmic reticulum stress pathway.

• 대한한의학방제학회지
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• 제31권3호
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• pp.183-191
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• 2023

Objective : UVB damages skin health by causing skin redness and intense inflammation, sunburn, and skin cancer. Paeoniae Radix Alba has been used to relieve gynecological symptoms, muscle spasms, and skin ailments. This study was conducted to confirm whether it has a protective effect against UVB photodamage. Methods : Ethanol extract of Paeoniae Radix Alba (PRA) was prepared by extracting 100 g Paeoniae Radix Alba in 1 L of ethanol for 48 h. Apoptosis was monitored by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and expression levels of apoptosis indicator proteins, and tyrosinase activity was measured with a colorimetric commercial kit. Results : In human keratinocyte HaCaT cells, PRA reduced UVB-induced cell death through apoptosis by inhibiting PARP cleavage and caspase-3 and -9. UVB-induced increase in cellular reactive oxygen species (ROS) was suppressed by PRA pretreatment. PRA also showed dose-dependent ABTS and DPPH radical scavenging activities. Furthermore, the inhibitory effect of tyrosinase activity by PRA was confirmed. Conclusion : These results demonstrated the protective role of PRA in UVB photodamage of human keratinocytes, mainly due to its antioxidant and antiapoptotic properties. We also suggest that PRA can be considered as an effective natural agent to prevent skin photodamage.