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21.
Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models
Heesun Choi Haeng Jun Kim Jinhee Yang Sehyun Chae Wonik Lee Sunwoo Chung Jisoo Kim Hyunjung Choi Hyeseung Song Chang Kon Lee Jae Hyun Jun Yong Jae Lee Kyunghyeon Lee Semi Kim Hye‐ri Sim Young Il Choi Keun Ho Ryu Jong‐Chan Park Dongjoon Lee Sun‐Ho Han Daehee Hwang Jangbeen Kyung Inhee Mook‐Jung 《Aging cell》2020,19(1)
Alzheimer's disease (AD) is an age‐related neurodegenerative disease. The most common pathological hallmarks are amyloid plaques and neurofibrillary tangles in the brain. In the brains of patients with AD, pathological tau is abnormally accumulated causing neuronal loss, synaptic dysfunction, and cognitive decline. We found a histone deacetylase 6 (HDAC6) inhibitor, CKD‐504, changed the tau interactome dramatically to degrade pathological tau not only in AD animal model (ADLPAPT) brains containing both amyloid plaques and neurofibrillary tangles but also in AD patient‐derived brain organoids. Acetylated tau recruited chaperone proteins such as Hsp40, Hsp70, and Hsp110, and this complex bound to novel tau E3 ligases including UBE2O and RNF14. This complex degraded pathological tau through proteasomal pathway. We also identified the responsible acetylation sites on tau. These dramatic tau‐interactome changes may result in tau degradation, leading to the recovery of synaptic pathology and cognitive decline in the ADLPAPT mice. 相似文献
22.
Jung‐Gu Han Chihyun Hwang Su Hwan Kim Chanhyun Park Jonghak Kim Gwan Yeong Jung Kyungeun Baek Sujong Chae Seok Ju Kang Jaephil Cho Sang Kyu Kwak Hyun‐Kon Song Nam‐Soon Choi 《Liver Transplantation》2020,10(20)
High‐capacity Li‐rich layered oxide cathodes along with Si‐incorporated graphite anodes have high reversible capacity, outperforming the electrode materials used in existing commercial products. Hence, they are potential candidates for the development of high‐energy‐density lithium‐ion batteries (LIBs). However, structural degradation induced by loss of interfacial stability is a roadblock to their practical use. Here, the use of malonic acid‐decorated fullerene (MA‐C60) with superoxide dismutase activity and water scavenging capability as an electrolyte additive to overcome the structural instability of high‐capacity electrodes that hampers the battery quality is reported. Deactivation of PF5 by water scavenging leads to the long‐term stability of the interfacial structures of electrodes. Moreover, an MA‐C60‐added electrolyte deactivates the reactive oxygen species and constructs an electrochemically robust cathode‐electrolyte interface for Li‐rich cathodes. This work paves the way for new possibilities in the design of electrolyte additives by eliminating undesirable reactive substances and tuning the interfacial structures of high‐capacity electrodes in LIBs. 相似文献
23.
Lee JunHyung Hosseindoust Abdolreza Kim MinJu Kim KwangYeol Choi YoHan Lee SeokHee Lee SongYi Cho HyunJong Kang Wei Soo Chae ByungJo 《Biological trace element research》2020,193(2):536-547
Biological Trace Element Research - In this study, the pattern of metals concentration in water, sediment, plants, and three edible fish species (Channa striata, Labeo rohita, and Catla catla) of... 相似文献
24.
Young Kwang Chae Han-Yao Huang Paul Strickland Sandra C. Hoffman Kathy Helzlsouer 《PloS one》2009,4(8)
Estrogen may be involved in the development of prostate cancer. The association between genetic polymorphisms of estrogen receptors α (ESR1) and β (ESR2) and prostate cancer risk was examined in a nested case-control study in Washington County, Maryland. Incident prostate cancer cases (n = 269) were matched to one or two controls (n = 440) by age, sex, race, and date of blood donation. Associations between estrogen receptor genotypes or dietary intake and the development of prostate cancer were examined in conditional logistic regression models. Results from this study showed that six single base-pair polymorphisms (SNPs) of ESR1 (rs1801132, rs2077647, rs746432, rs2273206, rs851982, rs2228480) and four SNPs of ESR2 (rs4986938, rs928554, rs8018687, rs number not available for ESR2 5696 bp 3′ of STP A>G) were not significantly associated with prostate cancer risk, either by allelic or genotypic frequencies. However, an interactive association with BMI was observed in the relationship between prostate cancer risk and genotypes of ESR2 38 bp 3′ of STP G>A (rs4986938) (p = 0.031). An interaction between intake level of phytoestrogen and genotypes of ESR1 Ex1-192G>C (rs746432) and between intake level of phytoestrogen and genotypes of ESR1 Ex8+229G>A (rs2228480) and risk of prostate cancer was observed (p = 0.0009 and p = 0.044, respectively). In conclusion, selected genetic polymorphisms of ESR1 and ESR2, overall, were not associated with prostate cancer risk. However, a variation in risk by BMI and phytoestrogen intake was implicated. 相似文献
25.
26.
Jung Eun Hwang Joon Ki Hong Ji Hyun Je Kyun Oh Lee Dool Yi Kim Sang Yeol Lee Chae Oh Lim 《Plant cell reports》2009,28(11):1623-1632
Phytocystatins are cysteine proteinase inhibitors in plants that are implicated in the endogenous regulation of protein turnover
and defense mechanisms against insects and pathogens. A cDNA encoding a phytocystatin called AtCYS6 (Arabidopsis thaliana phytocystatin6) has been isolated. We show that AtCYS6 is highly expressed in dry seeds and seedlings and that it also accumulates
in flowers. The persistence of AtCYS6 protein expression in seedlings was promoted by abscisic acid (ABA), a seed germination
and post-germination inhibitory phytohormone. This finding was made in transgenic plants bearing an AtCYS6 promoter–β-glucuronidase (GUS) reporter construct, where we found that expression from the AtCYS6 promoter persisted after ABA treatment but was reduced under control conditions and by gibberellin4+7 (GA4+7) treatment during the germination and post-germinative periods. In addition, constitutive over-expression of AtCYS6 retarded germination and seedling growth, whereas these were enhanced in an AtCYS6 knock-out mutant (cys6-2). Additionally, cysteine proteinase activities stored in seeds were inhibited by AtCYS6 in transgenic Arabidopsis. From these data, we propose that AtCYS6 expression is enhanced by the germination inhibitory phytohormone ABA and that it participates in the control of germination
rate and seedling growth by inhibiting the activity of stored cysteine proteinases. 相似文献
27.
Kang‐Young Choi Hyun‐Jung Kim Byung‐Chae Cho In‐San Kim Hyun‐Jung Kim Hyun‐Mo Ryoo 《Journal of cellular biochemistry》2009,107(4):818-825
TGF‐β3, TβR‐I, and TGF‐β‐activated Smad2 has been suggested to be a series of signaling molecules for secondary palate fusion. In this article, we show that a gene induced by TGF‐β, βig‐h3, is coincidentally expressed with TGF‐β3 in medial edge epithelial (MEE) cells undergoing apoptosis during normal palatal fusion. βig‐h3 was also highly expressed in the areas of post‐weaning mammary gland cells and developing phalangeal joints in which TGF‐β3 or BMP‐4‐induced apoptosis occurs, respectively. Blocking of βig‐h3 expression in E12.5 embryos with antisense oligodeoxynucleotides (ODN) resulted in cleft of the secondary palate in 84% of the treated mice that were born. Moreover, the antisense ODN treatment resulted in a failure of apoptosis in the MEE between palatal shelves in physical contact in organ culture. We conclude that βig‐h3 expression in the MEE is stimulated by TGF‐β3, causes cell death, and consequently results in complete fusion of the apposed palatal shelves. J. Cell. Biochem. 107: 818–825, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
28.
A new kinetic model of the Na+/H+ exchanger (NHE) was developed by fitting a variety of major experimental findings, such as ion-dependencies, forward/reverse mode, and the turnover rate. The role of NHE in ion homeostasis was examined by implementing the NHE model in a minimum cell model including intracellular pH buffer, Na+/K+ pump, background H+, and Na+ fluxes. This minimum cell model was validated by reconstructing recovery of pHi from acidification, accompanying transient increase in [Na+]i due to NHE activity. Based on this cell model, steady-state relationships among pHi, [Na+]I, and [Ca2+]i were quantitatively determined, and thereby the critical level of acidosis for cell survival was predicted. The acidification reported during partial blockade of the Na+/K+ pump was not attributed to a dissipation of the Na+ gradient across the membrane, but to an increase in indirect H+ production. This NHE model, though not adapted to the dimeric behavioral aspects of NHE, can provide a strong clue to quantitative prediction of degree of acidification and accompanying disturbance of ion homeostasis under various pathophysiological conditions. 相似文献
29.
30.
Jeong‐Han Kang Hyun‐Ji Cho In‐Seon Lee Moonkyu Kim In‐Kyu Lee Young‐Chae Chang 《Proteomics》2009,9(19):4445-4456
Transforming growth factor‐β1 (TGF‐β1) has a wide range of biological functions such as the regulation of cell growth, differentiation, and immunological response in various types of cells. Particularly, TGF‐β1 induces plasminogen activator inhibitor‐1 (PAI‐1) as a major target protein. PAI‐1 is associated with fibrosis, thrombosis, and metabolic disorders. In this study, to identify proteins potentially involved in TGF‐β1‐induced fibrosis processes, we performed a proteomic analysis of TGF‐β1‐induced normal rat kidney cells exposed to ascofuranone (AF). In these cells, we detected 1500 proteins, with 74 differentially expressed proteins identified by MALDI‐TOF and reference to the NCBI and Swiss‐Prot databases, including PAI‐1, peroxisome prdifesator‐activated receptor, prohibitin, glutamate formyltransferase, LIM domain protein 1, LASP‐1, porphobilinogen deaminase, and peroxiredoxin 2. We also found that AF suppresses expression of profibrotic factors induced by TGF‐β in renal fibroblasts, including matrix proteins and PAI‐1. AF was also shown to inhibit selectively phosphorylation of epidermal growth factor receptor, and downstream kinases such as extracellular signal‐regulated kinase 1/2 (ERK‐1/2). Further ongoing analysis of fibrosis‐related proteins will determine AF's potential for application in fibrotic diseases and therapeutics. 相似文献