Effects of Small Molecular Antioxidants on Choline-Deficient Ethionine Supplemented Diet-Induced Acute Pancreatitis in Mice

Background/Aims: It has been suggested that oxygen free radicals are involved in the initiation process of acute pancreatitis. In this study, we evaluated the role of oxygen radicals and the effect of small molecular antioxidants in the development of choline-deficient ethionine supplemented (CDE) diet-induced acute pancreatitis. Methods: Acute necrotizing pancreatitis was induced in young female ICR mice (12.5 ±1.9 g) by feeding CDE diet for 48 hours. Then, the effects of antioxidant (rebamipide, N-acetyl-cysteine, allopurinol,β-carotene, and combination of α-tocopherol and ascor bate) were examined. Results: CDE diet resulted in a significant increase in serum amylase level and the concentration of pancreatic malondialdehyde (MDA). It also caused pancreatic edema and in creased proinflammatory cytokines such as TNF-α, IL-6 and IL-1 βin serum. Treatment of rebami pide, or combination of α-tocopherol and ascorbate significantly decreased the CDE diet-induced pathophysiologic deterioration of pancreas. On the other hand, allopurinol,β-carotene and N-acetyl-cysteine showed little effect. Conclusions: These results indicate that oxygen free radicals play an important role in the development of acute pancreatitis. Antioxidants may ameliorate the CDE diet induced acute pancreatitis. Further evaluation of antioxidants such as rebamipide, combination of α-tocopherol and ascorbate is necessary for possible therapeutic application.ope

Manganese Superoxide Dismutase Deficiency Exacerbates Cerebral Infarction After Focal Cerebral Ischemia/Reperfusion in Mice Implications for the Production and Role of Superoxide Radicals

BACKGROUND AND PURPOSE: Superoxide anion radicals (O2*-) are implicated in ischemia/reperfusion injury, although a direct relationship has not been elucidated. Recently, a specific method of hydroethidine (HEt) oxidation by O2*- was developed to detect O2*- production in a variety of experimental brain injury models. To clarify the role of O2*- in the mechanism of ischemia/reperfusion, we investigated O2*- production after ischemia/reperfusion and ischemia/reperfusion injury in mutant mice deficient in mitochondrial manganese superoxide dismutase (MnSOD) and in wild-type littermates. METHODS: Ischemia/reperfusion was performed for 60 minutes using intraluminal suture blockade of the middle cerebral artery in the mutant or wild-type mice. We evaluated fluorescent kinetics of HEt or ethidium, the oxidized form of HEt, in brains after an intravenous injection of HEt, followed by measurement of cellular O2*- production using specific HEt oxidation by O2*- before and after ischemia/reperfusion. Furthermore, we compared O2*- production and subsequent infarct volume in the mice using triphenyltetrazolium chloride after ischemia/reperfusion. RESULTS: HEt oxidation to ethidium is primarily a result of mitochondrially produced O2*- under physiological conditions. Cerebral ischemia/reperfusion produced O2*- prominently in neurons shortly after reperfusion, followed by a delayed increase in endothelial cells. A deficiency in MnSOD in mutant mice increased mitochondrial O2*- production and exacerbated cerebral infarction, worsening neurological deficits after ischemia/reperfusion. CONCLUSION: These results suggest that mitochondrial O2*- production may be a critical step underlying the mechanism of ischemia/reperfusion injury and that MnSOD may protect against ongoing oxidative cell death after ischemia/reperfusion.ope

An Empirical Study on the Amount of Cash Holdings in Korean Ocean-going Shipping Companies Before and After 2008 Global Financial Crisis

본 연구는 기업의 현금보유수준에 관한 실증연구를 국적외항선사의 글로벌 금융위기 전·후를 고려한 패널 데이터 분석을 이용해 분석해 보고자 한다. 기업은 미래의 불확실성을 가진 상황에 대비하기 위해 다양한 방법을 가지고 있다. 부채를 줄여 향후 기업의 비용을 줄이거나 유동성을 가진 현금성 자산 등을 늘려 발생되는 비용을 대비할 수도 있다. 특히, 해운 기업은 세계경제와 밀접한 연관이 있고 외환 및 금융시장 변동성에도 매우 민감한 기업형태를 가지고 있어 미래 불확실성에 대비한 현금보유수준에 대한 고려가 매우 중요하다고 볼 수 있다. 이를 바탕으로 국적 외항선사 43개 기업의 1999년부터 2017년까지 19년 동안의 자료를 분석한 결과는 다음과 같다. 첫째, Opler, et al.(1999)의 연구에서 기업의 현금보유수준은 일정한 수준의 목표치를 가진 다는 것을 이용하여 국적 외항선사에 적용하면 국적 외항선사도 일정 수준의 현금보유수준을 목표치로 갖고 있는 것으로 나타났다. 둘째, 글로벌 금융위기 전과 후에 현금보유수준 변동에 차이가 있는지를 분석한 결과 국적 외항선사의 현금보유수준은 글로벌 금융위기로 인하여 유의하게 증가하는 것으로 분석되었다. 기업의 현금흐름 변동성으로 측정한 기업별 위험은 다른 기업과 마찬가지로 국적 외항선사의 현금보유수준에 유의하게 양(+)의 영향을 주었다. 셋째, 일반 기업과 마찬가지로 국적 외항선사도 기업의 규모는 거래적 동기로써 기업의 현금보유 수준에 부(-)의 영향을 주었다. 그러나 국적 외항선사의 규모변수로 자산보다는 선박장부가의 규모가 더 의미가 있었다. 부채의 비용, 규모, 만기 모두 현금보유수준에 음(-)의 영향을 주었다. 규모보다는 비용과 만기 요인이 더 의미 있는 요인이었다. 기업의 성장 및 투자기회 확대에 관한 요인은 국적 외항선사에서는 유의한 결과를 얻지 못하였다. 미래 성장을 위한 자본조달로서의 현금보유보다는 생존을 위한 현금보유 동기가 더 큰 것으로 분석되었다. 본 연구는 세계 경제와 매우 밀접하고 변동성이 큰 특징을 가진 국적 외항선사의 현금보유 특성을 분석하고 글로벌 금융위기로 인한 국적 외항선사의 현금보유수준 변화를 분석하였다는데 의의를 가진다.|This study aims to analyze the empirical study on the cash holdings of company by using panel data analysis considering the before and after of global financial crisis of Korean Ocean-going shipping companies. The business have various means of preparations prior to future uncertainty. Paying down debt to reduce the next business operating expenses or increasing liquidity cashable assets may be a good ready for incurred expense. Shipping firms in particular has close connection with world economy that its business type is very sensitive to foreign exchange and financial market changes; therefore, taking the cash holdings for future uncertainty into consideration is very important. So with that, the following is the result of analyzing 43 Korean Ocean-going shipping companies for 19 years specifically from 1999 to 2017. Firstly, Opler, et al.(1999)’s study shows that the cash holdings of firm aims constant target level. Likewise, this study finds that it is also true with Korean Ocean-going shipping companies. Secondly, as a result of comparing with before and after of global financial crisis, the cash holdings of Korean Ocean-going shipping companies shows a significant change due to global financial crisis. Korean Ocean-going shipping companies’cash flow volatility affects positively on the cash holdings as same as the other established firms. Thirdly, as transactional motive, Korean Ocean-going shipping companies’ business scale negatively affects on the cash holdings like the other business. However, the size of the ship’s book value was more meaningful than the assets, when considering representative variable of size of Korean ocean-going shipping companies. The cost, size, and maturity of the debt have negative impact on the cash holdings. Cost and maturity are more significant factors than the size. The factors related to the growth of firms and the investment opportunities were not found to be significant in Korean Ocean-going shipping companies. This analyzation shows that the survival motivates the cash holdings more than the capital finance for future growth. This study is meaningful in analysing the characteristics of cash holdings of Korean Ocean-going shipping companies which are closely related to the global economy and have high volatility and the change of cash holdings by the global financial crisis.1. 서론 1.1 연구의 배경 및 목적 1 1.2 연구의 구성 6 2. 해운업의 특성 및 현황 2.1 해운업의 주기성 7 2.1.1 장기 해운경기 순환주기(Long shipping cycles) 7 2.1.2 단기 해운경기 순환주기(Short shipping cycles) 8 2.1.3 계절 해운경기 순환주기(Seasonal shipping cycles) 9 2.2 해운업의 수익 10 2.2.1 운임수익 10 2.2.1 대선수익 13 2.2.1 선박 매각 수익 14 2.3 해운업의 비용 15 2.3.1 선비(Operating costs) 15 2.3.2 정기검사비(Periodic maintenance costs) 16 2.3.3 운항비(Voyage costs) 16 2.3.4 화물 취급비(Cargo-handling costs) 17 2.3.5 자본비(Capital costs) 18 2.4 해운기업의 현금보유 특성 및 국내 현황 19 3. 이론적 배경 및 선행 연구 3.1 이론적 배경 21 3.2 선행 연구 23 4. 실증분석 4.1 패널데이터 분석 28 4.2 데이터 30 4.3 국적 외항선사의 현금보유 평균회귀성 30 4.4 변수 설정 및 추정 방법 32 4.5 실증분석 39 4.5.1 금융위기 효과 분석 39 4.5.2 금융위기 효과를 제외하고 기업별 위험을 고려한 분석 43 4.5.3 금융위기 효과와 기업별 위험을 함께 고려한 분석 46 4.5.4 기업별 위험과 금융위기 더미변수의 교호작용항을 포함한 분석 48 5. 결론 5.1 연구의 요약 및 결론 51 5.2 연구의 한계 및 향후과제 53 감사의 글 54 참고문헌 55Maste

Early Decrease in DNA Repair Proteins, Ku70 and Ku86, and Subsequent DNA Fragmentation After Transient Focal Cerebral Ischemia in Mice

BACKGROUND AND PURPOSE: Ku70 and Ku86, multifunctional DNA repair proteins, bind to broken DNA ends, including double-strand breaks, and trigger a DNA repair pathway. To investigate the involvement of these proteins in DNA fragmentation after ischemia/reperfusion, Ku protein expression was examined before and after transient focal cerebral ischemia (FCI) in mice. METHODS: Adult male CD-1 mice were subjected to 60 minutes of FCI by intraluminal suture blockade of the middle cerebral artery. Ku protein expression was studied by immunohistochemistry and Western blot analysis. DNA fragmentation was evaluated by gel electrophoresis and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL). The spatial relationship between Ku expression and DNA fragmentation was examined by double labeling with Ku and TUNEL after reperfusion. RESULTS: Immunohistochemistry showed constitutive expression of Ku proteins in control brains. The number of Ku-expressing cells was decreased in the entire middle cerebral artery territory as early as 4 hours after reperfusion and remained reduced until 24 hours. Western blot analyses confirmed the significant reduction of these proteins (59.4% and 57.7% reduction in optical density at 4 hours of reperfusion from the normal level of Ku70 and Ku86 bands, respectively; P<0.001). DNA gel electrophoresis demonstrated DNA laddering 24 hours after reperfusion, but not at 4 hours. Double staining with Ku and TUNEL showed a concomitant loss of Ku immunoreactivity and TUNEL-positive staining. CONCLUSIONS: These results suggest that the early reduction of Ku proteins and the loss of defense against DNA damage may underlie the mechanism of DNA fragmentation after FCI.ope

쇼그렌 증후군 마우스 모델에서 결막하 투여된 항HMGB1이 건성안에 미치는 영향

학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의학과, 2018. 2. 김미금.Purpose: Extracellular high mobility group box 1 (HMGB1) acts as a damage associated molecular pattern molecule through the Toll-like receptor (TLR) to promote autoreactive B cell activation, which may be involved in the pathogenesis of Sjӧgrens syndrome. Moreover, extracellularly secreted HMGB1 is reported to be involved in the activation of T helper (Th) 17 cells during inflammatory disease, and may also be involved in interleukin (IL)-17 or IL-22 secretion in innate lymphoid cells (ILCs) which have important functions in innate and adaptive immunity. Considering that TLR9 abundantly expressed on B cells and plasmacytoid dendritic cells and main role of reactive B cells and plasma cells that secrete autoantibodies in the pathogenesis of Sjӧgrens syndrome together, we hypothesized that chronic epithelial damage to the cornea or lacrimal gland may contribute to trigger the vicious cycle of inflammation by secreting HMGB1 as a danger signal. Therefore, this study was aimed to investigate the effect of subconjunctival administration of anti-HMGB1 antibodies on dry eye in a mouse model of Sjӧgrens syndrome via evaluation of changes in clinical manifestations of dry eye and immunologic responses. Methods: NOD.B10.H2b mice were used as primary Sjӧgrens syndrome model, and to investigate inhibitory effect of triggering by HMGB1 in early stage of inflammatory cascades, ten weeks-old mice were chosen based on previous preliminary data. Twenty-four mice were divided into 4 groups and anti-HMGB1 antibodies (0.02, 0.2 and 2 µg/0.1 cc) or phosphate buffered saline (PBS) containing chicken immunoglobulin Y (0.2 µg/0.1 cc) were injected subconjunctivally twice a week for two consecutive weeks. To evaluate changes in clinical manifestations, tear volume and corneal staining scores were measured and compared between before- and after-treatment. Goblet cell density was counted in periodic acid Schiff (PAS) stained forniceal conjunctiva. For the evaluation of changes in immunologic responses, flow cytometry was performed to evaluate the changes in BrdU+ cells, IL-17-, IL-10-, or IFNγ-secreting cells, functional B cells, and IL-22 secreting group 3 ILCs in cervical lymph nodes. The level of anti-SSA in plasma and IL-22 in intraorbital glands were also measured using enzyme-linked immunosorbent assay. Inflammatory foci score (>50 cells/focus) was measured in extraorbital glands after CD3 and B220 immunohistochemical staining. Results: Injection of 2 µg or 0.02 µg anti-HMGB1 antibodies significantly attenuated corneal epithelial erosions (p<0.05). Tear volume significantly increased in groups treated with 2 µg or 0.02 µg anti-HMGB1 antibodies (p<0.05). Although statistical significance was failed to be shown, clinical manifestation of corneal epithelial disruption and tear secretion tended to be improved in the 0.2 µg anti-HMGB1 antibodies treated group. Goblet cell density was increased in 0.2 µg and 2 µg anti-HMGB1-treated-mice with marginal significance. The percentage and number of BrdU+CD3+T and BrdU+B220+B cells in the draining lymph nodes of treated mice were not significantly altered compared to that in controls. For effector T cell responses, the percentage of Th17 cells and cytotoxic T cells that secret IL-17 were not different and IFNγ-secreting cells were not changed following treatment. For functional B cell responses, no significant changes were found in the percentage of plasma cells or regulatory B cells in the draining lymph nodes. Level of anti-SSA in plasma was not significantly changed. The infiltrating focus of CD3+T cells was very similar to that of B220+B cells in extraorbital gland and scores of inflammatory foci were not different among the groups. Unexpectedly, the percentage of group 3 ILCs was significantly increased in the draining lymph nodes (p<0.05), and the expression of IL-22 was significantly increased in the intraorbital glands (p<0.05) after administration of 2 µg anti-HMGB1. Conclusion: Subconjunctival administration of anti-HMGB1 improved clinical manifestations of dry eye in NOD.B10.H2b mice. The improvement of dry eye may involve an increase of group 3 ILCs, rather than modulation of B cells or plasma cells, as shown in the present study using a mouse model of Sjӧgrens syndrome.Chapter 1. Introduction 1 1.1. Study Background 1 1.2. Purpose of Research 6 Chapter 2. Materials and Methods 7 2.1. Animals 7 2.2. Mouse model of Sjӧgrens syndrome 7 2.3. Anti-HMGB1 treatment 8 2.4. BrdU proliferation analysis 8 2.5. Phenol red thread test for tear volume measurement 8 2.6. Corneal dye staining 9 2.7. Periodic acid Schiff (PAS) staining for identification of goblet cells 9 2.8. Histopathology 10 2.9. Flow cytometry 10 2.10. Enzyme-linked immunosorbent assay 12 2.11. Statistical analysis 12 Chapter 3. Results 13 3.1. Effect of anti-HMGB1 treatment on the clinical manifestation of dry eye 13 3.2. Changes in immunologic responses in the extraorbital glands, plasma, and draining lymph nodes 15 3.3. Changes in innate lymphoid cell type 3 in the draining lymph nodes 19 Chapter 4. Discussion 21 Chapter 5. Conclusion 26 Bibliography 27 Supporting Information 31 Abstract in Korean 35Docto

Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q

Apoptosis signal-regulating kinase-1 (ASK1), an early signaling element in the cell death pathway, has been hypothesized to participate in the pathology of neurodegenerative diseases. The systemic administration of 3-nitropropionic acid (3-NP) facilitates the development of selective striatal lesions. However, it remains unclear whether specific neurons are selectively targeted in 3-NP-infused striatal degeneration. Recently, it has been proposed that complement-mediated synapse elimination may be reactivated aberrantly in the pathology of neurodegenerative diseases. We hypothesized that ASK1 is involved in striatal astrocyte reactivation; reactive astrocyte secretes molecules detrimental to neuron; and striatal neurons are more susceptible to these factors. Our results indicate that striatal astrocyte is reactivated and ASK1 level increases after 3-NP general and chronic infusion. Reactive striatal astrocyte increases TGF-beta differentially to cortex and striatum. ASK1 may be involved in regulation of astrocyte TGF-beta and it is linked to the C1q level in spatial and temporal, and moreover in the earlier stage of progressing striatal neuronal loss. Conclusively the present study suggests that ASK1 mediates 3-NP toxicity and regulates C1q level through the astrocyte TGF-beta. And also it may suggest that C1q level may be a surrogate of prediction marker representing neurodegenerative disease progress before developing behavioral impairment.ope

핵 수용체 LXR의 공동 활성 조절자로서 AP-1과 NR1D1 연구

학위논문 (석사)-- 서울대학교 대학원 약학대학 약학과, 2017. 8. 이미옥.Liver X receptor (LXR) α and β are nuclear receptors that regulate genes controlling lipid metabolism in numerous tissues. LXRs have been suggested as a potential therapeutic target to treat various pathological disorders that are driven by lipid metabolism. Thus numerous efforts to find ligands and modulators that have the ability to regulate LXR activity are being made to treat diseases and have been highlighted. Therefore, we aimed to identify the modulators and molecular mechanisms which regulate LXR-mediated lipid metabolism in certain tissues. We found two cases of regulating the activity of LXR in skin and liver. First, in skin, Raffinose, an oligosaccharide, activated LXR transcriptional activity and induced genes involved in LXR-mediated lipid metabolism, water transport and keratinocyte differentiation through in vitro and in vivo study. However, Raffinose is not a ligand of LXRs. To elucidate the mechanism, we focused on the correlation between LXRs and AP-1 family that plays a critical role in keratinocyte survival and differentiation. Raffinose and TO901317 induced the expression of JunD and Fra1, and increased DNA binding of c-Jun on the AP-1 response element in the promoter of involucrin and loricrin. Interestingly, LXRs also bound to AP-1 sites after treatment with Raffinose and TO901317. JunD and Fra1 enhanced transcriptional function of LXR and increased expression of genes involved in LXR-mediated lipid metabolism. Therefore, the results of the first case suggest that Raffinose inducess AP-1 family, c-Jun, JunD and Fra1, which leads to the induction of LXR signaling and stimulation of keratinocyte differentiation. Secondly, in liver, we showed that nuclear receptor subfamily 1 , group D, member1 (NR1D1) upregulated genes of LXRα and SREBP1-c and induced transcriptional acitivity of LXRα and LXRβ. In vitro screening for finding NR1D1 ligand showed that Compound1 antagonizes transcriptional activity of NR1D1. This Compound1 suppressed transcriptional function of LXR as well as protein levels of LXR and LXR-mediated lipogenic genes. Taken together, our results suggest that as transactivating coregulators of LXR, AP-1 family and NR1D1 regulate lipid metabolism in skin and liver. Our observations may help applying on treating a variety of diseases.Ⅰ. INTRODUCTION １ Ⅱ. PURPOSE of the STUDY 9 Ⅲ. MATERIALS and METHODS 10 1. Cell lines and cell treatment 10 2. Reporter gene assay 10 3. Fluorescence resonance energy transfer (FRET)assay 11 4. Chromatin immunoprecipitation (ChIP) assay 11 5. Animal, tissue preparation and Immunohistochemistry in skin in vivo model 12 6. Quantitative real-time polymerase chain reaction (qRT-PCR) 13 7. Western blot assay 13 8. Statistical analysis 14 Ⅳ. RESULTS 16 1. Raffinose activates transcriptional function of LXR, but is not a ligand of LXR 16 2. Raffinose stimulates lipid metabolism and epidermal differentiation in the skin of Hairless mouse 19 3. Raffinose inducestranscription of genes involved in lipid metabolism and keratinocyte differentiation in HaCaT cell 21 4. AP-1 family are regulated by Raffinose and involved in keratinocyte differentiation 23 5. JunD and Fra1 enhance LXR signaling 26 6. NR1D1 regulate expression and transcriptional function of LXRs 29 7. In vitro Screening, the Compound1 antagonized trnascriptional function of NR1D1 29 8. The Compound1, NR1D1 suppresor, inhibits LXR signaling 35 Ⅴ. DISCUSSION 38 REFERENCE 43 국문초록 47Maste

Neuronal Expression of the DNA Repair Protein Ku 70 After Ischemic Preconditioning Corresponds to Tolerance to Global Cerebral Ischemia

BACKGROUND AND PURPOSE: Oxidative stress after ischemia/reperfusion has been shown to induce DNA damage and subsequent DNA repair activity. Ku 70/86, multifunctional DNA repair proteins, bind to broken DNA ends and trigger a DNA repair pathway. We investigated the involvement of these proteins in the development of neuronal tolerance to global cerebral ischemia after ischemic preconditioning. METHODS: Adult male Sprague-Dawley rats were subjected to either 5 minutes of lethal global ischemia with or without 3 minutes of sublethal ischemic preconditioning or 3 minutes of ischemia only. Neuronal injury was histologically assessed, and DNA damage was visualized by in situ labeling of DNA fragmentation and DNA gel electrophoresis. Ku expression was also examined by immunohistochemistry and Western blot analysis. RESULTS: Hippocampal CA1 neurons underwent DNA-fragmented cell death 3 days after 5 minutes of ischemia. However, these neurons showed a strong tolerance to 5 minutes of ischemia 1 to 3 days after ischemic preconditioning. Immunohistochemistry showed virtually no constitutive expression of Ku proteins in CA1 neurons; however, ischemic preconditioning induced neuronal Ku 70 expression 1 to 3 days later. Western blot confirmed an increase in Ku 70 in this region at the same time. CONCLUSIONS: The temporal and spatial expression of Ku 70 corresponded to tolerance of the hippocampal CA1 neurons to subsequent ischemia, suggesting the involvement of Ku proteins in the development of neuronal tolerance after ischemic preconditioning.ope

15-deoxy-D12,14-prostaglandin J2 suppresses RANTES expression by inhibiting NADPH oxidase activation in Helicobacter pylori-infected gastric epithelial cells

Peroxisome proliferators-activated receptor-γ (PPAR-γ) is a ligand-activated transcription factor. 15 deoxy-(12,14) prostaglandin J(2) (15d-PGJ(2)) is a potent PPAR-γ ligand and acts as an anti-inflammatory agent via PPAR-γ-dependent and independent mechanisms. Helicobacter pylori (H. pylori) induces gastric inflammation by inducing the activation of oxidant-sensitive transcription factor NF-κB and cytokine expression in gastric epithelial cells. Since 15d-PGJ(2) inhibits NF-κB activation in various cells, it may suppress H. pylori-induced inflammatory signaling and cytokine expression in gastric epithelial cells. The present study aims to determined the effect of 15d-PGJ(2) on the activation of inflammatory mediators Jak/Stat (Janus kinase/signal transducers and activators of transcription) and induction of cytokine RANTES in H. pylori-infected gastric epithelial AGS cells. Since NADPH oxidase is a candidate for the production of reactive oxygen species in H. pylori-infected gastric epithelial cells, we determined the effect of 15d-PGJ(2) on the activation of NADPH oxdase. AGS cells were cultured in the presence of H. pylori treated with or without 15d-PGJ(2). The activations of NADPH oxidase and Jak1/Stat3, the levels of H(2)O(2) and RANTES in the medium, and DNA binding activity of Stat3 were assessed. A Jak/Stat3 specific inhibitor AG490 and an inhibitor of NADPH oxidase diphenyleneiodonium (DPI) were treated to determine the direct involvement of Jak/Stat and NADPH oxidase on the production of H(2)O(2) and RANTES in H. pylori-infected cells. H. pylori induced the production of H(2)O(2) and RANTES as well as the activations of NADPH oxidase and Jak1/Stat3, which were inhibited by the treatment of 15d-PGJ(2). DPI suppressed H. pylori-induced alterations similar to 15d-PGJ(2). However, AG490 had no effect on NADPH oxidase activation, but reduced the level of RANTES in the medium released from H. pylori-infected cells. Conclusion: NADPH oxidase activation is an upstream signaling of Jak1/Stat3 activation and induction of RANTES in H. pylori-infected AGS cells. 15d-PGJ(2), inhibits the activations of NADPH oxidase and Jak1/Stat3 and RANTES expression, suggesting that 15d-PGJ(2) may be beneficial for the treatment of H. pylori-induced gastric inflammation.ope

Involvement of superoxide in excitotoxicity & DNA fragmentation in straiatal vulnerability in mice after treatment with the mitochondrial toxin, 3-NP

Oxidative stress and excitotoxicity have been implicated in selective striatal vulnerability caused by the mitochondrial toxin, 3-nitropropionic acid (3-NP), which may simulate Huntington's disease in animals and humans. The detailed mechanism of the role of superoxide in striatal vulnerability induced by 3-NP is still unknown. The authors investigated oxidative cellular injury and DNA fragmentation after systemic 3-NP injection in wild-type (Wt) mice and mutant mice with a deficiency in manganese superoxide dismutase (MnSOD; Sod2 -/+). Furthermore, they investigated the effects of decortication after 3-NP treatment in Sod2 -/+ mice, and copper/zinc SOD (CuZnSOD) treatment in recently developed Sod2 -/+ mice that overexpress CuZnSOD (SOD1 +/- / Sod2 -/+ mice). Oxidized hydroethidine, 8-hydroxyguanosine immunoreactivity, and nitrotyrosine immunoreactivity were increased in the Sod2 -/+ mice compared with the Wt mice after 3-NP treatment (P < 0.001). Decortication completely abolished oxidative striatal damage after 3-NP treatment in the Sod2 -/+ mice. Increased CuZnSOD attenuated DNA fragmentation and striatal lesion volume after 3-NP treatment in the Sod2 -/+ mice (P < 0.001). These data suggest that production of superoxide may be a critical step to excitotoxicity and subsequent DNA fragmentation in selective striatal vulnerability after 3-NP treatment.ope