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121.
Bing Pan Yijing Ma Hui Ren Yubin He Yongyu Wang Xiaofeng Lv Donghui Liu Liang Ji Baoqi Yu Yuhui Wang Y. Eugene Chen Subramaniam Pennathur Jonathan D. Smith George Liu Lemin Zheng 《PloS one》2012,7(11)
Background
Diabetic HDL had diminished capacity to stimulate endothelial cell (EC) proliferation, migration, and adhesion to extracellular matrix. The mechanism of such dysfunction is poorly understood and we therefore sought to determine the mechanistic features of diabetic HDL dysfunction.Methodology/Principal Findings
We found that the dysfunction of diabetic HDL on human umbilical vein endothelial cells (HUVECs) was associated with the down regulation of the HDL receptor protein, SR-BI. Akt-phosphorylation in HUVECs was induced in a biphasic manner by normal HDL. While diabetic HDL induced Akt phosphorylation normally after 20 minutes, the phosphorylation observed 24 hours after diabetic HDL treatment was reduced. To determine the role of SR-BI down regulation on diminished EC responses of diabetic HDL, Mouse aortic endothelial cells (MAECs) were isolated from wild type and SR-BI (−/−) mice, and treated with normal and diabetic HDL. The proliferative and migratory effects of normal HDL on wild type MAECs were greatly diminished in SR-BI (−/−) cells. In contrast, response to diabetic HDL was impaired in both types suggesting diminished effectiveness of diabetic HDL on EC proliferation and migration might be due to the down regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL’s capacity to activate Akt chronically.Conclusions/Significance
Diabetic HDL was dysfunctional in promoting EC proliferation, migration, and adhesion to matrix which was associated with the down-regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL’s capacity to activate Akt chronically. 相似文献122.
S Mitra S Lukianov WG Ruiz C Cianciolo Cosentino S Sanker LM Traub NA Hukriede G Apodaca 《PloS one》2012,7(7):e41816
Uroplakin (UP)3a is critical for urinary tract development and function; however, its role in these processes is unknown. We examined the function of the UP3a-like protein Upk3l, which was expressed at the apical surfaces of the epithelial cells that line the pronephric tubules (PTs) of the zebrafish pronephros. Embryos treated with upk3l-targeted morpholinos showed decreased pronephros function, which was attributed to defects in PT epithelial cell morphogenesis and polarization including: loss of an apical brush border and associated phospho-ERM proteins, apical redistribution of the basolateral Na(+)/K(+)-ATPase, and altered or diminished expression of the apical polarity complex proteins Prkcz (atypical protein kinase C zeta) and Pard3 (Par3). Upk3l missing its C-terminal cytoplasmic domain or containing mutations in conserved tyrosine or proline residues did not rescue, or only partially rescued the effects of Upk3l depletion. Our studies indicate that Upk3l promotes epithelial polarization and morphogenesis, likely by forming or stimulating interactions with cytoplasmic signaling or polarity proteins, and that defects in this process may underlie the pathology observed in UP3a knockout mice or patients with renal abnormalities that result from altered UP3a expression. 相似文献
123.
Treatment of blood loss with plasma expanders lowers blood viscosity, increasing cardiac output. However, increased flow velocity by conventional plasma expanders does not compensate for decreased viscosity in maintaining vessel wall shear stress (WSS), decreasing endothelial nitric oxide (NO) production. A new type of plasma expander using polyethylene glycol conjugate albumin (PEG-Alb) causes supra-perfusion when used in extreme hemodilution and is effective in treating hemorrhagic shock, although it is minimally viscogenic. An acute 40% hemodilution/exchange-transfusion protocol was used to compare 4% PEG-Alb to Ringer's lactate, Dextran 70 kDa and 6% Hetastarch (670 kDa) in unanesthetized CD-1 mice. Serum cytokine analysis showed that PEG-Alb elevates monocyte chemotactic protein-1 (MCP-1), a member of a small inducible gene family, as well as expression of MIP-1α, and MIP-2. MCP-1 is specific to increased WSS. Given the direct link between increased WSS and production of NO, the beneficial resuscitation effects due to PEG-Alb plasma expansion appear to be due to increased WSS through increased perfusion and blood flow rather than blood viscosity. 相似文献
124.
Membrane disruption by oligomeric α-synuclein (αS) is considered a likely mechanism of cytotoxicity in Parkinson’s disease (PD). However, the mechanism of oligomer binding and the relation between binding and membrane disruption is not known. We have visualized αS oligomer-lipid binding by fluorescence microscopy and have measured membrane disruption using a dye release assay. The data reveal that oligomeric αS selectively binds to membranes containing anionic lipids and preferentially accumulates into liquid disordered (Ld) domains. Furthermore, we show that binding of oligomers to the membrane and disruption of the membrane require different lipid properties. Thus membrane-bound oligomeric αS does not always cause bilayer disruption. 相似文献
125.
Transforming growth factor-β (TGF-β) and glial-cell-line-derived neurotrophic factor (GDNF) have been shown to synergize in
several paradigms of neuronal survival. We have previously shown that cerebellar granule neurons (CGN) degenerate in low potassium
via ERK1/2 (extra-cellular-regulated kinase)-dependent plasma membrane (PM) damage and caspase-3-dependent DNA fragmentation.
Here, we have investigated the putative synergistic function of GDNF and TGF-β in CGN degeneration. GDNF alone prevents low-potassium-induced
caspase-3 activation and DNA fragmentation but does not affect either low-potassium-induced ERK activation or PM damage. TGF-β
alone does not affect low-potassium-induced DNA fragmentation but potentiates low-potassium-induced PM damage. This effect
of TGF-β is independent of ERK1/2 activation but dependent on p38-MAPK (mitogen-activated protein kinase) activation. When
co-applied with TGF-β, GDNF paradoxically antagonizes TGF-β-induced potentiation of PM damage by inhibiting TGF-β-induced
p38-MAPK activation. In addition, PI3K (phosphatidylinositol 3-kinase) inhibitors abolish the GDNF effect. This study thus
demonstrates a differential mechanism of action of GDNF and TGF-β on CGN degeneration. GDNF inhibits caspase-3-dependent DNA
fragmentation but does not affect ERK-dependent PM damage. However, GDNF can attenuate TGF-β-induced p38-MAPK-dependent PM
damage via the PI3K pathway.
This work was supported by the Deutsche Forschungsgemeinschaft (STR 616/1–2) and by a fellowship (Young Investigator Award)
from the Medical Faculty, University of Heidelberg, Germany to S. Subramaniam. 相似文献
126.
Wallace DF Summerville L Crampton EM Subramaniam VN 《American journal of physiology. Cell physiology》2008,294(2):C383-C390
Transferrin receptor 2 (TfR2), a homologue of transferrin receptor 1 (TfR1), is a key molecule involved in the regulation of iron homeostasis. Mutations in TfR2 result in iron overload with similar features to HFE-associated hereditary hemochromatosis. The precise role of TfR2 in iron metabolism and the functional consequences of disease-causing mutations have not been fully determined. We have expressed wild-type and various mutant forms of TfR2 that are associated with human disease in a mouse liver cell line. Intracellular and surface analysis shows that all the TfR2 mutations analyzed cause the intracellular retention of the protein in the endoplasmic reticulum, whereas the wild-type protein is expressed in endocytic structures and at the cell surface. Our results indicate that the majority of mutations that cause type 3 hereditary hemochromatosis are a consequence of the defective localization of the protein. 相似文献
127.
R. D. Jebakumar Solomon Subramaniam Kallidass Jayaraj Vimalan 《World journal of microbiology & biotechnology》2005,21(6-7):1231-1236
Summary Fresh, dried and powdered samples of leaf, stem and root of Acalypha indica were subjected to fractional distillation in a soxhlet apparatus using solvents such as hexane, chloroform, acetone and methanol.
The plant extracts and a synthetic antifungal compound, Clotrimazole (authentic standard) were subjected to TLC and HPLC analyses.
The Rf (relative front) value of Clotrimazole was 0.371. The plant’s leaf, root and stem extracts also gave distinct spots respectively
at Rf value of 0.371 ± 0.0009. In HPLC, the TLC-separated active compound and Clotrimazole resolved at 1.90 ± 0.2 min (retention
time). The amounts of active compound present in root, leaf and stem extracts were 538, 415 and 171 μg/g respectively. From the results of our study, we infer that the active compound isolated from Acalypha indica is more potent in controlling Candida albicans, Aspergillus niger and Escherichia coli. The Active compound present in the plant had more than 100% activity when compared to standard Clotrimazole. 相似文献
128.
129.
Imidazolonepropionase (HutI) (imidazolone-5-propanote hydrolase, EC 3.5.2.7) is a member of the amidohydrolase superfamily and catalyzes the conversion of imidazolone-5-propanoate to N-formimino-L-glutamate in the histidine degradation pathway. We have determined the three-dimensional crystal structures of HutI from Agrobacterium tumefaciens (At-HutI) and an environmental sample from the Sargasso Sea Ocean Going Survey (Es-HutI) bound to the product [ N-formimino-L-glutamate (NIG)] and an inhibitor [3-(2,5-dioxoimidazolidin-4-yl)propionic acid (DIP)], respectively. In both structures, the active site is contained within each monomer, and its organization displays the landmark feature of the amidohydrolase superfamily, showing a metal ligand (iron), four histidines, and one aspartic acid. A catalytic mechanism involving His265 is proposed on the basis of the inhibitor-bound structure. This mechanism is applicable to all HutI forms. 相似文献
130.
Dirk Fasshauer Wolfram Antonin Vinod Subramaniam Reinhard Jahn 《Nature structural biology》2002,9(2):144-151
SNARE proteins are essential for intracellular membrane fusion of eukaryotes. Their assembly into stable four-helix bundles bridges membranes and may provide the energy for initiating membrane fusion. In vitro, assembly of soluble SNARE fragments is accompanied by major structural rearrangements that can be described as a folding reaction. The pathways and the thermodynamics of SNARE protein interactions, however, are not known. Here we report that assembly and dissociation of two distantly related SNARE complexes exhibit a marked hysteresis. The assembled and disassembled native states are separated by a kinetic barrier and cannot equilibrate on biologically relevant timescales. We suggest that the hysteresis is a hallmark of all SNARE complexes and that complex assembly and disassembly follow different pathways that may be independently controlled. 相似文献