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51.
Cong Cao Mengia S. Rioult-Pedotti Paolo Migani Crystal J. Yu Rakesh Tiwari Keykavous Parang Mark R. Spaller Dennis J. Goebel John Marshall 《PLoS biology》2013,11(2)
Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and a high rate of autism. AS is caused by disrupted neuronal expression of the maternally inherited Ube3A ubiquitin protein ligase, required for the proteasomal degradation of proteins implicated in synaptic plasticity, such as the activity-regulated cytoskeletal-associated protein (Arc/Arg3.1). Mice deficient in maternal Ube3A express elevated levels of Arc in response to synaptic activity, which coincides with severely impaired long-term potentiation (LTP) in the hippocampus and deficits in learning behaviors. In this study, we sought to test whether elevated levels of Arc interfere with brain-derived neurotrophic factor (BDNF) TrkB receptor signaling, which is known to be essential for both the induction and maintenance of LTP. We report that TrkB signaling in the AS mouse is defective, and show that reduction of Arc expression to control levels rescues the signaling deficits. Moreover, the association of the postsynaptic density protein PSD-95 with TrkB is critical for intact BDNF signaling, and elevated levels of Arc were found to impede PSD-95/TrkB association. In Ube3A deficient mice, the BDNF-induced recruitment of PSD-95, as well as PLCγ and Grb2-associated binder 1 (Gab1) with TrkB receptors was attenuated, resulting in reduced activation of PLCγ-α-calcium/calmodulin-dependent protein kinase II (CaMKII) and PI3K-Akt, but leaving the extracellular signal-regulated kinase (Erk) pathway intact. A bridged cyclic peptide (CN2097), shown by nuclear magnetic resonance (NMR) studies to uniquely bind the PDZ1 domain of PSD-95 with high affinity, decreased the interaction of Arc with PSD-95 to restore BDNF-induced TrkB/PSD-95 complex formation, signaling, and facilitate the induction of LTP in AS mice. We propose that the failure of TrkB receptor signaling at synapses in AS is directly linked to elevated levels of Arc associated with PSD-95 and PSD-95 PDZ-ligands may represent a promising approach to reverse cognitive dysfunction. 相似文献
52.
Ying Lu Qiao Zhou Yongbing Shi Jian Liu Fang Zhong Xu Hao Cong Li Nan Chen Weiming Wang 《PloS one》2013,8(11)
Rosiglitazone (RGL), a synthetic agonist for peroxisome proliferator activated receptor γ (PPARγ), exhibits a potent anti-inflammatory activity by attenuating local infiltration of neutrophils and monocytes in the renal interstitium. To evaluate the mechanisms that account for inhibiting inflammatory cells infiltration, we investigated the effect of RGL on chemokines secretion and nuclear factor-kappa B (NF-κB) activation in human renal proximal tubular cells (PTCs). We demonstrated that RGL significantly inhibited lipopolysaccharide (LPS)-induced interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) production in a dose-dependent manner, without appreciable cytotoxicity. Chromatin immunoprecipitation (ChIP) assays clearly revealed that, RGL inhibited p65 binding to IL-8/MCP-1 gene promoters in LPS-stimulated PTCs. Interestingly, further experiments showed RGL reversed LPS-induced nuclear receptor corepressor (NCoR) degradation. In addition, knockdown of protein inhibitor of activated STAT1 (PIAS1), an indispensable small ubiquitin-like modifier (SUMO) ligase, abrogated the effects of RGL on antagonizing LPS-induced IL-8/MCP-1 overexpression and NCoR degradation. These findings suggest that, RGL activates PPARγ SUMOylation, inhibiting NCoR degradation and NF-κB activation in LPS-stimulated PTCs, which in turn decrease chemokines expression. The results unveil a new mechanism triggered by RGL for prevention of tubular inflammatory injury. 相似文献
53.
Dam construction causes the accumulation of phosphorus in the sediments of reservoirs and increases the release rate of internal phosphorus (P) loading. This study investigated the longitudinal variability of phosphorus fractions in sediments and the relationship between the contents of phosphorus fractions and its influencing factors of the Manwan Reservoir, Lancang River, Yunnan Province, China. Five sedimentary phosphorus fractions were quantified separately: loosely bound P (ex-P); reductant soluble P (BD-P); metal oxide-bound P (NaOH-P); calcium-bound P (HCl-P), and residual-P. The results showed that the total phosphorus contents ranged from 623 to 899 µg/g and were correlated positively with iron content in the sediments of the reservoir. The rank order of P fractions in sediments of the mainstream was HCl-P>NaOH-P>residual-P>BD-P>ex-P, while it was residual-P>HCl-P>NaOH-P>BD-P>ex-P in those of the tributaries. The contents of bio-available phosphorus in the tributaries, including ex-P, BD-P and NaOH-P, were significantly lower than those in the mainstream. The contents of ex-P, BD-P, NaOH-P showed a similar increasing trend from the tail to the head of the Manwan Reservoir, which contributed to the relatively higher content of bio-available phosphorus, and represents a high bio-available phosphorus releasing risk within a distance of 10 km from Manwan Dam. Correlation and redundancy analyses showed that distance to Manwan Dam and the silt/clay fraction of sediments were related closely to the spatial variation of bio-available phosphorus. 相似文献
54.
Severe retinal ischemia causes persistent visual impairments in eye diseases. Retinal pigment epithelium (RPE) cells are located near the choroidal capillaries, and are easily affected by ischemic or hypoxia. Ginsenoside Rg-1 has shown significant neuroprotective effects. This study was performed to test the cytoprotective effect of ginsenoside Rg-1 in RPE cells against hypoxia and cobalt chloride (CoCl2) assaults, and to understand the underlying mechanisms. We found that Rg-1 pre-administration significantly inhibited CoCl2- and hypoxia-induced RPE cell death and apoptosis. Reactive oxygen specisis (ROS)-dependent p38 and c-Jun NH(2)-terminal kinases (JNK) MAPK activation was required for CoCl2-induced RPE cell death, and Rg-1 pre-treatment significantly inhibited ROS production and following p38/JNK activation. Further, CoCl2 suppressed pro-survival mTOR complex 1 (mTORC1) activation in RPE cells through activating of AMP-activated protein kinase (AMPK), while Rg-1 restored mTORC1 activity through inhibiting AMPK activation. CoCl2-induced AMPK activation was also dependent on ROS production, and anti-oxidant N-acetylcysteine (NAC) prevented AMPK activation and RPE cell death by CoCl2. Our results indicated that Rg-1 could be further investigated as a novel cell-protective agent for retinal ischemia. 相似文献
55.
Chamber tests are usually used to determine the source characteristics of semi-volatile organic compounds (SVOCs) which are critical to quantify indoor exposure to SVOCs. In contrast to volatile organic compounds (VOCs), the sorption effect of SVOCs to chamber surfaces usually needs to be considered due to the much higher surface/air partition coefficients, resulting in a long time to reach steady state, frequently on the order of months, and complicating the mathematical analysis of the resulting data. A chamber test is also complicated if the material-phase concentration is not constant. This study shows how to design a chamber to overcome these limitations. A dimensionless mass transfer analysis is used to specify conditions for (1) neglecting the SVOC sorption effect to chamber surfaces, (2) neglecting the convective mass transfer resistance at sorption surfaces if the sorption effect cannot be neglected, and (3) regarding the material-phase concentration in the source as constant. Several practical and quantifiable ways to improve chamber design are proposed. The approach is illustrated by analyzing available data from three different chambers in terms of the accuracy with which the model parameters can be determined and the time needed to conduct the chamber test. The results should greatly facilitate the design of chambers to characterize SVOC emissions and the resulting exposure. 相似文献
56.
57.
LncRNA LEF1-AS1 promotes osteogenic differentiation of dental pulp stem cells via sponging miR-24-3p
Molecular and Cellular Biochemistry - Alzheimer’s disease (AD) is the leading cause of dementia, which characterized by toxic senile plaques is composed of amyloid-β (Aβ).... 相似文献
58.
Liu Yuan Luo Cong Zhang Xiu-Juan Lu Xin-Xi Yu Hai-Xia Xie Xiao-Jie Fan Zhi-Yi Mo Xiao He Xin-Hua 《Plant Cell, Tissue and Organ Culture》2020,143(1):219-228
Plant Cell, Tissue and Organ Culture (PCTOC) - CONSTANS (CO)/CONSTANS-like (COL) genes play an important role in the photoperiodic flowering pathway. However, the functional roles of the CO/COL... 相似文献
59.
Dingsheng Liu Hong Zhang Jinchun Cong Mingming Cui Mingxing Ma Fangyuan Zhang Huayi Sun Chunsheng Chen 《Journal of cellular biochemistry》2020,121(2):1923-1933
Long noncoding RNAs (lncRNAs) are found to be aberrantly expressed and pose significant impacts in colorectal cancer (CRC), the most prevalent type malignancy in the gastrointestinal tract. This study aimed to find out the regulation of lncRNA EIF3J antisense RNA 1 (EIF3J-AS1) on CRC progression. Expressions of EIF3J-AS1, microRNA-3163 (miR-3163), and Yes-associated protein 1 (YAP1) in tissues and cells were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Association of EIF3J-AS1 with CRC prognosis was analyzed through the online bioinformatics tool GEPIA. The biological function of EIF3J-AS1 in CRC was investigated by Cell Counting Kit-8, colony formation, caspase-3 activity, and TUNEL staining. Competitive endogenous RNA (ceRNA) network of EIF3J-AS1/miR-3163/YAP1 was determined by luciferase reporter and RNA immunoprecipitation assays. Results showed that EIF3J-AS1 was upregulated in CRC tissues and cell lines, indicating poor prognosis of CRC patients. The silence of EIF3J-AS1 led to reduced proliferation and facilitated apoptosis of CRC cells. Mechanistcally, EIF3J-AS1 was upregulated by cAMP-response element-binding protein-binding protein-mediated histone H3 on lysine 27 acetylation (H3K27ac) at the promoter region, and EIF3J-AS1 upregulated YAP1 expression through sponging miR-3163 in CRC cells. In conclusion, we first found that H3K27 acetylation-induced lncRNA EIF3J-AS1 improved proliferation and impeded apoptosis of colorectal cancer through the miR-3163/YAP1 axis, which might potentially provide a novel molecular-targeted strategy for CRC treatment. 相似文献
60.