The FASEB Journal最新文献_第4页

Treadmill exercise alleviates brain iron dyshomeostasis accelerating neuronal amyloid‐β production, neuronal cell death and cognitive impairment in transgenic mice model of Alzheimer’s disease 在阿尔茨海默病转基因小鼠模型中，跑步机运动可缓解大脑铁失衡，加速神经元淀粉样蛋白-β的生成、神经元细胞死亡和认知障碍

The FASEB Journal Pub Date : 2020-04-01 DOI: 10.1096/fasebj.2020.34.s1.09298

Dong-Hun Choi, Ki-chun Kwon, Dong-Ju Hwang, Hyun-Seob Um, Jung‐hoon Koo, Eung-Jun Kim, D. Yeom, Joon-Yong Cho

{"title":"Treadmill exercise alleviates brain iron dyshomeostasis accelerating neuronal amyloid‐β production, neuronal cell death and cognitive impairment in transgenic mice model of Alzheimer’s disease","authors":"Dong-Hun Choi, Ki-chun Kwon, Dong-Ju Hwang, Hyun-Seob Um, Jung‐hoon Koo, Eung-Jun Kim, D. Yeom, Joon-Yong Cho","doi":"10.1096/fasebj.2020.34.s1.09298","DOIUrl":"https://doi.org/10.1096/fasebj.2020.34.s1.09298","url":null,"abstract":"Brain iron increases with age and brain iron dyshomeostasis is proving increasingly likely to be involved in the pathology of Alzheimer’s disease (AD) and Parkinson’s disease (PD), possibly via promoting oxidative damage. There is therefore an urgent need to research into improving role iron play in AD. Sustained exercise may be ways to slow the rate of overload of iron, by perhaps alleviating oxidative stress due to the Fenton reaction. Yet, the exact mechanisms of the effects of exercise on iron toxicity are not well understood. Here, we explored whether treadmill exercise impacts the AD‐related mechanism(s) of brain iron status in vivo, using APP‐C105 AD‐model mice. We observed iron‐induced disruptions of amyloid precursor protein (APP) processing, neuronal apoptotic signaling, oxidative stress, and cognitive impairment in APP‐C105 AD‐model mice. Further, brain iron dyshomeostasis associated with Aβ‐induced neuronal cell death possibly via APP misprocessing, and oxidative stress and cognitive decline was blocked by treadmill exercise, suggesting effect led to mitigated Aβ‐induced neuronal cell death and cognitive decline by promoting non‐amyloidogenic pathway possibly via enhanced furin, concomitant with inhibiting oxidative stress possibly via down‐regulating brain iron dyshomeostasis. Together, we show evidences to suggest that treadmill exercise may be ways to inhibit Aβ‐induced neuronal cell death by up‐regulating non‐amyloidogenic pathway through enhanced furin, concomitant with down‐regulating iron‐mediated oxidative stress.","PeriodicalId":22447,"journal":{"name":"The FASEB Journal","volume":" 31","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141219117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The interaction between p53 and Mdm2 is independent of MEG3–p53 association p53 和 Mdm2 之间的相互作用与 MEG3-p53 关联无关

The FASEB Journal Pub Date : 2020-04-01 DOI: 10.1096/fasebj.2020.34.s1.09899

Nicholas C. Bauer, Anli Yang, Xin Wang, Yunli Zhou, A. Klibanski, R. Soberman

引用次数: 1

Pleiotropic Activation of Endothelial Function by Angiotensin II Receptor Blockers is Crucial to Their Protective Anti‐vascular Remodeling Effects 血管紧张素 II 受体阻滞剂对内皮功能的多重激活是其保护性抗血管重塑作用的关键所在

The FASEB Journal Pub Date : 2020-04-01 DOI: 10.1096/fasebj.2020.34.s1.02011

Arash Y. Tehrani, N. Fameli, Zoe White, Mitra Esfandiarei, Casey van Breemen, Pascal Bernatchez

引用次数: 0

Effects of Lycopene on Growth Factor Response in Prostate Cancer Cells 番茄红素对前列腺癌细胞生长因子反应的影响

The FASEB Journal Pub Date : 2020-04-01 DOI: 10.1096/fasebj.2020.34.s1.00112

Mary P. Nivison, Allegra VanderWilde, Pravita Balijepalli, Kathryn E. Meier

{"title":"Effects of Lycopene on Growth Factor Response in Prostate Cancer Cells","authors":"Mary P. Nivison, Allegra VanderWilde, Pravita Balijepalli, Kathryn E. Meier","doi":"10.1096/fasebj.2020.34.s1.00112","DOIUrl":"https://doi.org/10.1096/fasebj.2020.34.s1.00112","url":null,"abstract":"Dietary and nutritional factors are considered critical modulating factors in prostate cancer development. Epidemiological data have suggested to the idea that dietary consumption of lycopene, found in tomatoes, may prevent prostate cancer. This study examined the mechanism by which lycopene interacts with prostate cancer cells, with the goal of discovering less toxic treatment and prevention options. The hypothesis that was addressed was that lycopene interferes with growth factor‐mediated signal transduction in prostate cancer cells. The effects of lycopene on PC‐3, a human prostate cancer cell line, were analyzed using proliferation assays, immunoblot analysis, and confocal microscopy. The growth factors used were lysophosphatidic acid (LPA) and epidermal growth factor (EGF). Lycopene (10 μM) inhibited LPA and EGF‐induced proliferation of PC‐3 cells, confirming previous unpublished results. Lycopene also inhibited activation of Akt in response to LPA and EGF as assessed by immunoblotting. Confocal immunofluorescence microscopy showed that the decrease in activated Akt was most prominent in the cell nucleus. These results confirm the ability of lycopene to inhibit growth factor response in human prostate cancer cells, and suggest new directions for future studies.","PeriodicalId":22447,"journal":{"name":"The FASEB Journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89112038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

In Memoriam: Gerald Weissmann 纪念:杰拉德·魏斯曼

The FASEB Journal Pub Date : 2019-09-01 DOI: 10.1096/fj.190901ufm

T. Pederson

引用次数: 1

Intraluminal delivery of thrombospondin‐2 small interfering RNA inhibits the vascular response to injury in a rat carotid balloon angioplasty model 在大鼠颈动脉球囊血管成形术模型中，腔内递送血栓反应蛋白- 2小干扰RNA抑制血管对损伤的反应

The FASEB Journal Pub Date : 2017-01-01 DOI: 10.1096/fj.201600501r

Thomas C. F. Bodewes, Joel M. Johnson, M. Auster, C. Huynh, Sriya Muralidharan, M. Contreras, F. Logerfo, Leena Pradhan-Nabzdyk

{"title":"Intraluminal delivery of thrombospondin‐2 small interfering RNA inhibits the vascular response to injury in a rat carotid balloon angioplasty model","authors":"Thomas C. F. Bodewes, Joel M. Johnson, M. Auster, C. Huynh, Sriya Muralidharan, M. Contreras, F. Logerfo, Leena Pradhan-Nabzdyk","doi":"10.1096/fj.201600501r","DOIUrl":"https://doi.org/10.1096/fj.201600501r","url":null,"abstract":"In an effort to inhibit the response to vascular injury that leads to intimal hyperplasia, this study investigated the in vivo efficacy of intraluminal delivery of thrombospondin‐2 (TSP‐2) small interfering RNA (siRNA). Common carotid artery (CCA) balloon angioplasty injury was performed in rats. Immediately after denudation, CCA was transfected intraluminally (15 min) with one of the following: polyethylenimine (PEI)+TSP‐2 siRNA, saline, PEI only, or PEI+control siRNA. CCA was analyzed at 24 h or 21 d by using quantitative real‐time PCR and immunohistochemistry. TSP‐2 gene and protein expression were significantly up‐regulated after endothelial denudation at 24 h and 21 d compared with contralateral untreated, nondenuded CCA. Treatment with PEI+TSP‐2 siRNA significantly suppressed TSP‐2 gene expression (3.1‐fold) at 24 h and TSP‐2 protein expression, cell proliferation, and collagen deposition up to 21 d. These changes could be attributed to changes in TGF‐β and matrix metalloproteinase‐9, the downstream effectors of TSP‐2. TSP‐2 knockdown induced anti‐inflammatory M2 macrophage polarization at 21 d; however, it did not significantly affect intima/media ratios. In summary, these data demonstrate effective siRNA transfection of the injured arterial wall and provide a clinically effective and translationally applicable therapeutic strategy that involves nonviral siRNA delivery to ameliorate the response to vascular injury.—Bodewes, T.C.F., Johnson, J.M., Auster, M., Huynh, C., Muralidharan, S., Contreras, M., LoGerfo, F. W., Intraluminal delivery of thrombospondin‐2 small interfering RNA inhibits the vascular response to injury in a rat carotid balloon angioplasty model. FASEB J. 31, 109–119 (2017) www.fasebj.org","PeriodicalId":22447,"journal":{"name":"The FASEB Journal","volume":"13 1","pages":"109 - 119"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84380181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Protective effects of mitochondria‐targeted antioxidants and statins on cholesterolinduced osteoarthritis 线粒体靶向抗氧化剂和他汀类药物对胆固醇性骨关节炎的保护作用

The FASEB Journal Pub Date : 2017-01-01 DOI: 10.1096/fj.201600600r

S. Farnaghi, I. Prasadam, G. Cai, T. Friis, Zhibin Du, R. Crawford, Xinzhan Mao, Yin Xiao

{"title":"Protective effects of mitochondria‐targeted antioxidants and statins on cholesterolinduced osteoarthritis","authors":"S. Farnaghi, I. Prasadam, G. Cai, T. Friis, Zhibin Du, R. Crawford, Xinzhan Mao, Yin Xiao","doi":"10.1096/fj.201600600r","DOIUrl":"https://doi.org/10.1096/fj.201600600r","url":null,"abstract":"The contribution of metabolic factors on the severity of osteoarthritis (OA) is not fully appreciated. This study aimed to define the effects of hyper cholesterolemia on the progression of OA. A polipoprotein E‐deficient (ApoE−/−) mice and rats with diet‐induced hypercholesterolemia (DIHC) rats were used to explore the effects of hyper cholesterolemia on the progression of OA. Both models exhibited OA‐like changes, characterized primarily by a loss of proteoglycans, collagen and aggrecan degradation, osteophyte formation, changes to subchondral bone architecture, and cartilage degradation. Surgical destabilization of the knees resulted in a dramatic increase of degradative OA symptoms in animals fed a high‐cholesterol diet compared with controls. Clinically relevant doses of free cholesterol resulted in mitochondrial dysfunction, overproduction of reactive oxygen species (ROS), and increased expression of degenerative and hypertrophic markers in chondrocytes and breakdown of the cartilage matrix. We showed that the severity of diet‐induced OA changes could be attenuated by treatment with both atorvastatin and a mitochondrial targeting antioxidant. The protective effects of the mitochondrial targeting antioxidant were associated with suppression of oxidative damage to chondrocytes and restoration of extracellular matrix homeostasis of the articular chondrocytes. In summary, our data show that hypercholesterolemia precipitates OA progression by mitochondrial dysfunction in chondrocytes, in part by increasing ROS production and apoptosis. By addressing the mitochondrial dysfunction using antioxidants, we were able attenuate the OA progression in our animal models. This approach may form the basis for novel treatment options for this OA risk group in humans.—Farnaghi, S., Prasadam, I., Cai, G., Friis, T., Du, Z., Crawford, R., Mao, X., Xiao, Y. Protective effects of mitochondria‐targeted antioxidants and statins on cholesterolinduced osteoarthritis. FASEB J. 31, 356–367 (2017) www.fasebj.org","PeriodicalId":22447,"journal":{"name":"The FASEB Journal","volume":"37 1","pages":"356 - 367"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84910626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 61

Acute lung injury is reduced by the α7nAChR agonist PNU‐282987 through changes in the macrophage profile α7nAChR激动剂PNU‐282987通过改变巨噬细胞谱减少急性肺损伤

The FASEB Journal Pub Date : 2017-01-01 DOI: 10.1096/fj.201600431r

Nathalia M Pinheiro, F. R. Santana, R. R. Almeida, M. Guerreiro, M. Martins, L. Caperuto, N. Câmara, L. A. Wensing, V. Prado, I. Tiberio, Marco Antônio M. Prado, C. Prado

{"title":"Acute lung injury is reduced by the α7nAChR agonist PNU‐282987 through changes in the macrophage profile","authors":"Nathalia M Pinheiro, F. R. Santana, R. R. Almeida, M. Guerreiro, M. Martins, L. Caperuto, N. Câmara, L. A. Wensing, V. Prado, I. Tiberio, Marco Antônio M. Prado, C. Prado","doi":"10.1096/fj.201600431r","DOIUrl":"https://doi.org/10.1096/fj.201600431r","url":null,"abstract":"Nicotinic α‐7 acetylcholine receptor (nAChRα7) is a critical regulator of cholinergic anti‐inflammatory actions in several diseases, including acute respiratory distress syndrome(ARDS). Given the potential importance of α7nAChR as a therapeutic target, we evaluated whether PNU‐282987, an α7nAChR agonist, is effective in protecting the lung against inflammation. We performed intratracheal instillation of LPS to generate acute lung injury (ALI) in C57BL/6 mice. PNU‐282987 treatment, either before or after ALI induction, reduced neutrophil recruitment and IL‐ 1β, TNF‐α, IL‐6, keratinocyte chemoattractant (KC), and IL‐10 cytokine levels in the bronchoalveolar lavage fluid (P> 0.05). In addition, lung NF‐κB phosphorylation decreased, along with collagen fiber deposition and the number of matrix metalloproteinase‐9+ and −2+ cells, whereas the number of tissue inhibitor of metalloproteinase‐1+ cells increased (P < 0.05). PNU‐282987 treatment also reduced lung mRNA levels and the frequency of M1 macrophages, whereas cells expressing the M2‐related markers CD206 and IL‐10 increased, suggesting changes in the macrophage profile. Finally, PNU‐282987 improved lung function in LPS‐treated animals. The collective results suggest that PNU‐282987, anagonist of α7nAChR, reducesLPS‐induced experimental ALI, thus supporting the notion that drugs that act on α7nAChRs should be explored for ARDS treatment in humans.—Pinheiro, N. M., Santana, F. P. R., Almeida, R. R., Guerreiro, M., Martins, M.A., Caperuto, L.C., Câmara, N.O.S., Wensing, L.A., Prado, V. F., Tibério, I. F. L. C., Prado, M.A.M., Prado, C. M. Acute lung injury is reduced by the α7nAChR agonist PNU‐282987 through changes in the macrophage profile. FASEB J. 31, 320–332 (2017) www.fasebj.org","PeriodicalId":22447,"journal":{"name":"The FASEB Journal","volume":"21 1","pages":"320 - 332"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78893339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 68

Professor Naba Gupta (1934–1997)

The FASEB Journal Pub Date : 1998-03-01 DOI: 10.1096/fasebj.12.3.390

K. Chakraburtty, J. Hershey

引用次数: 0