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91.
N-ethylmaleimide sensitive factor (NSF) is an ATPases associated with various cellular activities protein (AAA), broadly required for intracellular membrane fusion. NSF functions as a SNAP receptor (SNARE) chaperone which binds, through soluble NSF attachment proteins (SNAPs), to SNARE complexes and utilizes the energy of ATP hydrolysis to disassemble them thus facilitating SNARE recycling. While this is a major function of NSF, it does seem to interact with other proteins, such as the AMPA receptor subunit, GluR2, and beta2-AR and is thought to affect their trafficking patterns. New data suggest that NSF may be regulated by transient post-translational modifications such as phosphorylation and nitrosylation. These new aspects of NSF function as well as its role in SNARE complex dynamics will be discussed. 相似文献
92.
The angiotensin II type I (AT(1)) receptor mediates regulation of blood pressure and water-electrolyte balance by Ang II. Substitution of Gly for Asn(111) of the AT(1) receptor constitutively activates the receptor leading to Gq-coupled IP(3) production independent of Ang II binding. The Ang II-activated conformation of the AT1(N111G) receptor was proposed to be similar to that of the wild-type AT(1) receptor, although, various aspects of the Ang II-induced conformation of this constitutively active mutant receptor have not been systematically studied. Here, we provide evidence that the conformation of the active state of the wild-type and the constitutively active AT(1) receptors are different. Upon Ang II binding an activated conformation of the wild-type AT(1) receptor activates G protein and recruits beta-arrestin. In contrast, the agonist-bound AT1(N111G) mutant receptor preferentially couples to Gq and is inadequate in beta-arrestin recruitment. 相似文献
93.
A thorough understanding of histone acetyltransferase CBP/p300-mediated regulation of gene expression and cell growth is essential to identify mechanisms relevant to the development of histone deacetylase (HDAC) inhibitor-based preventive and therapeutic strategies. We found that knockdown of CBP/p300 interacting coactivator with glutamic acid/aspartic acid-rich tail 2 (CITED2) increased colon cancer cell invasiveness in vitro. Gene expression profiling revealed that CITED2 knockdown induced matrix metalloproteinase-13 (MMP-13) gene expression in colon cancer cells. Butyrate, a naturally occurring HDAC inhibitor, induced CITED2 expression and downregulated MMP-13 expression in RKO cells. Additionally, ectopic expression of CITED2 arrested RKO cell growth. Thus, CITED2 regulates colon cancer invasion and might be a target for HDAC inhibitor-based intervention of colon cancer. 相似文献
94.
Nijikken Y Tsukada T Igarashi K Samejima M Wakagi T Shoun H Fushinobu S 《FEBS letters》2007,581(7):1514-1520
The white-rot fungus Phanerochaete chrysosporium has two intracellular beta-glucosidases (BGL1A and BGL1B) belonging to glycoside hydrolase (GH) family 1. BGL1B effectively hydrolyzes cellobiose and cellobionolactone, but BGL1A does not. We have determined the crystal structure of BGL1A in substrate-free and gluconolactone complexed forms. The overall structure and the characteristic of subsite -1 (glycone site) were similar to those of other known GH1 enzymes. The loop regions covering on the (beta/alpha)(8) barrel was significantly deviated, and they form a unique subsite +1 (aglycone site) of BGL1A. 相似文献
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97.
Md. Sahab Uddin Abdullah Al Mamun Zubair Khalid Labu Oscar Hidalgo-Lanussa George E. Barreto Ghulam Md Ashraf 《Journal of cellular physiology》2019,234(6):8094-8112
Autophagy is a preserved cytoplasmic self-degradation process and endorses recycling of intracellular constituents into bioenergetics for the controlling of cellular homeostasis. Functional autophagy process is essential in eliminating cytoplasmic waste components and helps in the recycling of some of its constituents. Studies have revealed that neurodegenerative disorders may be caused by mutations in autophagy-related genes and alterations of autophagic flux. Alzheimer’s disease (AD) is an irrevocable deleterious neurodegenerative disorder characterized by the formation of senile plaques and neurofibrillary tangles (NFTs) in the hippocampus and cortex. In the central nervous system of healthy people, there is no accretion of amyloid β (Aβ) peptides due to the balance between generation and degradation of Aβ. However, for AD patients, the generation of Aβ peptides is higher than lysis that causes accretion of Aβ. Likewise, the maturation of autophagolysosomes and inhibition of their retrograde transport creates favorable conditions for Aβ accumulation. Furthermore, increasing mammalian target of rapamycin (mTOR) signaling raises tau levels as well as phosphorylation. Alteration of mTOR activity occurs in the early stage of AD. In addition, copious evidence links autophagic/lysosomal dysfunction in AD. Compromised mitophagy is also accountable for dysfunctional mitochondria that raises Alzheimer’s pathology. Therefore, autophagic dysfunction might lead to the deposit of atypical proteins in the AD brain and manipulation of autophagy could be considered as an emerging therapeutic target. This review highlights the critical linkage of autophagy in the pathogenesis of AD, and avows a new insight to search for therapeutic target for blocking Alzheimer’s pathogenesis. 相似文献
98.
Xiumei Chen Jianzhong Lin Tingting Hu Zhiyun Ren Linnan Li Irbaz Hameed Xiaoyu Zhang Chen Men Yan Guo Di Xu Yiyang Zhan 《Journal of cellular physiology》2019,234(7):10990-11000
Oxidized low-density lipoprotein (Ox-LDL)-induced endothelial cell injury plays a crucial role in the pathogenesis of atherosclerosis (AS). Plasma galectin-3 (Gal-3) is elevated inside and drives diverse systemic inflammatory disorders, including cardiovascular diseases. However, the exact role of Gal-3 in ox-LDL-mediated endothelial injury remains unclear. This study explores the effects of Gal-3 on ox-LDL-induced endothelial dysfunction and the underlying molecular mechanisms. In this study, Gal-3, integrin β1, and GTP-RhoA in the blood and plaques of AS patients were examined by ELISA and western blot respectively. Their levels were found to be obviously upregulated compared with non-AS control group. CCK8 assay and flow cytometry analysis showed that Gal-3 significantly decreased cell viability and promoted apoptosis in ox-LDL-treated human umbilical vascular endothelial cells (HUVECs). The upregulation of integrinβ1, GTP-RhoA, p-JNK, p-p65, p-IKKα, and p-IKKβ induced by ox-LDL was further enhanced by treatment with Gal-3. Pretreatment with Gal-3 increased expression of inflammatory factors (interleukin [IL]-6, IL-8, and IL-1β), chemokines(CXCL-1 and CCL-2) and adhesion molecules (VCAM-1 and ICAM-1). Furthermore, the promotional effects of Gal-3 on NF-κB activation and inflammatory factors in ox-LDL-treated HUVECs were reversed by the treatments with integrinβ1-siRNA or the JNK inhibitor. We also found that integrinβ1-siRNA decreased the protein expression of GTP-RhoA and p-JNK, while RhoA inhibitor partially reduced the upregulated expression of p-JNK induced by Gal-3. In conclusion, our finding suggests that Gal-3 exacerbates ox-LDL-mediated endothelial injury by inducing inflammation via integrin β1-RhoA-JNK signaling activation. 相似文献
99.
Multiple studies have reported different methods in treating gestational diabetes mellitus (GDM); however, the relationship between miR-335-5p and GDM still remains unclear. Here, this study explores the effect of miR-335-5p on insulin resistance and pancreatic islet β-cell secretion via activation of the TGFβ signaling pathway by downregulating VASH1 expression in GDM mice. The GDM mouse model was established and mainly treated with miR-335-5p mimic, miR-335-5p inhibitor, si-VASH1, and miR-335-5p inhibitor + si-VASH1. Oral glucose tolerance test (OGTT) was conducted to detect fasting blood glucose (FBG) fasting insulin (FINS). The OGTT was also used to calculate a homeostasis model assessment of insulin resistance (HOMA-IR). A hyperglycemic clamp was performed to measure the glucose infusion rate (GIR), which estimated β-cell function. Expressions of miR-335-5p, VASH1, TGF-β1, and c-Myc in pancreatic islet β-cells were determined by RT-qPCR, western blot analysis, and insulin release by ELISA. The miR-335-5p mimic and si-VASH1 groups showed elevated blood glucose levels, glucose area under the curve (GAUC), and HOMA-IR, but a reduced GIR and positive expression of VASH1. Overexpression of miR-335-5p and inhibition of VASH1 contributed to activated TGFβ1 pathway, higher c-Myc, and lower VASH1 expressions, in addition to downregulated insulin and insulin release levels. These findings provided evidence that miR-335-5p enhanced insulin resistance and suppressed pancreatic islet β-cell secretion by inhibiting VASH1, eventually activating the TGF-β pathway in GDM mice, which provides more clinical insight on the GDM treatment. 相似文献
100.
Alzheimer’s disease (AD) is a multifaceted neurodegenerative disorder affecting the elderly people. For the AD treatment, there is inefficiency in the existing medication, as these drugs reduce only the symptoms of the disease. Since multiple pathological proteins are involved in the development of AD, searching for a single molecule targeting multiple AD proteins will be a new strategy for the management of AD. In view of this, the present study was designed to synthesize and evaluate the multifunctional neuroprotective ability of the sesquiterpene glycoside α-bisabolol β-D-fucopyranoside (ABFP) against multiple targets like acetylcholinesterase, oxidative stress and β-amyloid peptide aggregation induced cytotoxicity. In silico computational docking and simulation studies of ABFP with acetylcholinesterase (AChE) showed that it can interact with Asp74 and Thr75 residues of the enzyme. The in vitro studies showed that the compound possess significant ability to inhibit the AChE enzyme apart from exhibiting antioxidant, anti-aggregation and disaggregation properties. In addition, molecular dynamics simulation studies proved that the interacting residue between Aβ peptide and ABFP was found to be involved in Leu34 and Ile31. Furthermore, the compound was able to protect the Neuro2 a cells against Aβ25-35 peptide induced toxicity. Overall, the present study evidently proved ABFP as a neuroprotective agent, which might act as a multi-target compound for the treatment of Alzheimer’s disease. 相似文献