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https://www.readbyqxmd.com/read/28542204/similar-regulatory-mechanisms-of-caveolins-and-cavins-by-myocardin-family-coactivators-in-arterial-and-bladder-smooth-muscle
#1
Baoyi Zhu, Catarina Rippe, Tran Thi Hien, Jianwen Zeng, Sebastian Albinsson, Karin G Stenkula, Bengt Uvelius, Karl Swärd
Caveolae are membrane invaginations present at high densities in muscle and fat. Recent work has demonstrated that myocardin family coactivators (MYOCD, MKL1), which are important for contractile differentiation and cell motility, increase caveolin (CAV1, CAV2, CAV3) and cavin (CAVIN1, CAVIN2, CAVIN3) transcription, but several aspects of this control mechanism remain to be investigated. Here, using promoter reporter assays we found that both MKL1/MRTF-A and MKL2/MRTF-B control caveolins and cavins via their proximal promoter sequences...
2017: PloS One
https://www.readbyqxmd.com/read/28542134/phosphorylated-cav1-activates-autophagy-through-an-interaction-with-becn1-under-oxidative-stress
#2
Jihoon Nah, Seung-Min Yoo, Sunmin Jung, Eun Il Jeong, Moonju Park, Bong-Kiun Kaang, Yong-Keun Jung
CAV1/Caveolin1, an integral membrane protein, is involved in caveolae function and cellular signaling pathways. Here, we report that CAV1 is a positive regulator of autophagy under oxidative stress and cerebral ischemic injury. Treatment with hydrogen peroxide enhanced autophagy flux and caused the localization of BECN1 to the mitochondria, whereas these changes were impaired in the absence of CAV1. Among many autophagy signals, only LC3 foci formation in response to hydrogen peroxide was abolished by CAV1 deficiency...
May 25, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28540373/in-vitro-cellular-behaviors-and-toxicity-assays-of-small-sized-fluorescent-silicon-nanoparticles
#3
Zhaohui Cao, Fei Peng, Zhilin Hu, Binbin Chu, Yiling Zhong, Yuanyuan Su, Sudan He, Yao He
Extensive investigations have been carried out for evaluating the toxicology of various nanomaterials (e.g., carbon- and metal-based nanomaterials), which offer invaluable information for assessing the feasibility of nanomaterial-based wide-ranging applications. In recent years, sufficient efforts have been made to develop fluorescent small-sized silicon nanoparticles (SiNPs) as a novel optical material simultaneously featuring strong fluorescence and ultrahigh photostability, providing high promise for a myriad of biological, biomedical and electronic applications...
May 25, 2017: Nanoscale
https://www.readbyqxmd.com/read/28540174/a-preliminary-study-on-the-interaction-between-asn-gly-arg-ngr-modified-multifunctional-nanoparticles-and-vascular-epithelial-cells
#4
Chunxi Liu, Tingxian Liu, Xiaoyue Yu, Yizhu Gu
Previously developed Asn-Gly-Arg (NGR) peptide-modified multifunctional poly(ethyleneimine)-poly(ethylene glycol) (PEI-PEG)-based nanoparticles (TPIC) have been considered to be promising carriers for the co-delivery of DNA and doxorubicin (DOX). As a continued effort, the aim of the present study was to further evaluate the interaction between TPIC and human umbilical vein endothelial cells (HUVEC) to better understand the cellular entry mechanism. In the present investigation, experiments relevant to co-localization, endocytosis inhibitors and factors influencing the internalization were performed...
May 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28539337/altered-expression-and-modulation-of-the-two-pore-domain-k2p-mechano-gated-potassium-channel-trek-1-in-overactive-human-detrusor
#5
Ricardo H Pineda, Balachandar Nedumaran, Joseph A Hypolite, Xiao-Qing Pan, Shandra Wilson, Randall B Meacham, Anna P Malykhina
Background Detrusor overactivity (DO) is the abnormal response of the urinary bladder to physiological stretch during the filling phase of the micturition cycle. The mechanisms of bladder smooth muscle compliance upon the wall stretch are poorly understood. We previously reported that the function of normal detrusor is regulated by TREK-1, a member of the mechano-gated subfamily of two-pore domain potassium (K2P) channels. In the present study, we aimed to identify the changes in expression and function of TREK-1 channels under pathological conditions associated with DO, evaluate the potential relationship between TREK-1 channels and cytoskeletal proteins in the human bladder, and test the possibility of modulation of TREK-1 channel expression by small RNAs...
May 24, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28516168/selective-surface-pegylation-of-uio-66-nanoparticles-for-enhanced-stability-cell-uptake-and-ph-responsive-drug-delivery
#6
Isabel Abánades Lázaro, Salame Haddad, Sabrina Sacca, Claudia Orellana-Tavra, David Fairen-Jimenez, Ross S Forgan
The high storage capacities and excellent biocompatibilities of metal-organic frameworks (MOFs) have made them emerging candidates as drug-delivery vectors. Incorporation of surface functionality is a route to enhanced properties, and here we report on a surface-modification procedure-click modulation-that controls their size and surface chemistry. The zirconium terephthalate MOF UiO-66 is (1) synthesized as ∼200 nm nanoparticles coated with functionalized modulators, (2) loaded with cargo, and (3) covalently surface modified with poly(ethylene glycol) (PEG) chains through mild bioconjugate reactions...
April 13, 2017: Chem
https://www.readbyqxmd.com/read/28501784/cellular-uptake-mechanism-and-clearance-kinetics-of-fluorescence-labeled-glycyrrhetinic-acid-and-glycyrrhetinic-acid-modified-liposome-in-hepatocellular-carcinoma-cells
#7
Yuqi Sun, Jinghua Lu, Dongxue Yan, Liping Shen, Haiyang Hu, Dawei Chen
Glycyrrhetinic acid (GA) is a natural pentacyclic triterpene derivative that exerts significant effects in the suppression of liver cancer. The receptors of GA on liver cells and hepatocellular carcinoma (HCC) cells have drawn broad attention. The effects of GA might depend on its transport into and out of cells. However, the question has not been previously addressed despite its obvious and fundamental importance. In this paper, GA and GA-modified liposome (GA-Lip) were labeled with fluorescein isothiocyanate (FITC) or coumarin 6 (Cou6) using chemical or pharmaceutical techniques...
May 5, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28500977/endocytosis-and-intracellular-traffic-of-cholesterol-pdmaema-liposome-complexes-in-human-epithelial-like-cells
#8
F Szymanowski, A A Hugo, P Alves, P N Simões, A Gómez-Zavaglia, Pablo F Pérez
Liposomes are generally used as delivery systems, as they are capable of encapsulating a wide variety of molecules (i.e. plasmids, recombinant proteins, therapeutic drugs). However, liposomal drug delivery have to fulfill different requirements, such as the effective internalization by the target cells and avoidance of the degradative activity of the intracellular compartments. The use of polymer lipid complexes (PLCs), by including different polymers in the liposome formulation, could improve internalization and intracellular release of drugs...
May 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28498861/modulation-of-caveolins-integrins-and-plasma-membrane-repair-proteins-in-anthracycline-induced-heart-failure-in-rabbits
#9
Yasuhiro Ichikawa, Alice E Zemljic-Harpf, Zheng Zhang, M Dan McKirnan, Ana Maria Manso, Robert S Ross, H Kirk Hammond, Hemal H Patel, David M Roth
Anthracyclines are chemotherapeutic drugs known to induce heart failure in a dose-dependent manner. Mechanisms involved in anthracycline cardiotoxicity are an area of relevant investigation. Caveolins bind, organize and regulate receptors and signaling molecules within cell membranes. Caveolin-3 (Cav-3), integrins and related membrane repair proteins can function as cardioprotective proteins. Expression of these proteins in anthracycline-induced heart failure has not been evaluated. We tested the hypothesis that daunorubicin alters cardioprotective protein expression in the heart...
2017: PloS One
https://www.readbyqxmd.com/read/28498322/valproic-acid-induces-endocytosis-mediated-doxorubicin-internalization-and-shows-synergistic-cytotoxic-effects-in-hepatocellular-carcinoma-cells
#10
Subbroto Kumar Saha, Yingfu Yin, Kyeongseok Kim, Gwang-Mo Yang, Ahmed Abdal Dayem, Hye Yeon Choi, Ssang-Goo Cho
Valproic acid (VPA), a well-known histone deacetylase (HDAC) inhibitor, is used as an anti-cancer drug for various cancers, but the synergistic anti-cancer effect of VPA and doxorubicin (DOX) combination treatment and its potential underlying mechanism in hepatocellular carcinoma (HCC) remain to be elucidated. Here, we evaluate the mono- and combination-therapy effects of VPA and DOX in HCC and identify a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line...
May 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28497682/size-dependent-regulation-of-intracellular-trafficking-of-polystyrene-nanoparticle-based-drug-delivery-systems
#11
Ting Wang, Lu Wang, Xiaoming Li, Xingjie Hu, Yuping Han, Yao Luo, Zejun Wang, Qian Li, Ali Aldalbahi, Lihua Wang, Shiping Song, Chunhai Fan, Yun Zhao, Maolin Wang, Nan Chen
Nanoparticles (NPs) have shown great promise as intracellular imaging probes or nanocarriers and are increasingly being used in biomedical applications. A detailed understanding of how NPs get "in and out" of cells is important for developing new nanomaterials with improved selectivity and less cytotoxicity. Both physical and chemical characteristics have been proven to regulate the cellular uptake of NPs. However, the exocytosis process and its regulation are less explored. Herein, we investigated the size-regulated endocytosis and exocytosis of carboxylated polystyrene (PS) NPs...
May 24, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28493563/nalmefene-prevents-alcohol-induced-neuroinflammation-and-alcohol-drinking-preference-in-adolescent-female-mice-role-of-tlr4
#12
Jorge Montesinos, Anabel Gil, Consuelo Guerri
BACKGROUND: We previously showed that, by activating innate immune receptors toll-like 4 (TLR4), adolescent intermittent ethanol exposure causes neuroinflammation, myelin damage and behavioral dysfunctions. Recent findings reveal that clinically-used opioid antagonists naltrexone (NT) and naloxone (NX) inhibit opioid-induced TLR4 signaling, and that NT, NX and nalmefene (NF), the 6-methylene derivative of NX, are able to reduce alcohol drinking escalation. METHODS: NF (0...
May 11, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28490792/length-effects-on-the-dynamic-process-of-cellular-uptake-and-exocytosis-of-single-walled-carbon-nanotubes-in-murine-macrophage-cells
#13
Xuejing Cui, Bin Wan, Yu Yang, Xiaomin Ren, Liang-Hong Guo
Cellular uptake and exocytosis of SWCNTs are fundamental processes determining their intracellular concentration and effects. Despite the great potential of acid-oxidized SWCNTs in biomedical field, understanding of the influencing factors on these processes needs to be deepened. Here, we quantitatively investigated uptake and exocytosis of SWCNTs in three lengths-630 (±171) nm (L-SWCNTs), 390 (±50) nm (M-SWCNTs), and 195 (±63) nm (S-MWCNTs) in macrophages. The results showed that the cellular accumulation of SWCNTs was a length-independent process and non-monotonic in time, with the most SWCNTs (3950 fg/cell) accumulated at 8 h and then intracellular SWCNTs dropped obviously with time...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28489581/high-glucose-induces-formation-of-tau-hyperphosphorylation-via-cav-1-mtor-pathway-a-potential-molecular-mechanism-for-diabetes-induced-cognitive-dysfunction
#14
Jing Wu, Shan-Lei Zhou, Lin-Hua Pi, Xia-Jie Shi, Ling-Ran Ma, Zi Chen, Min-Li Qu, Xin Li, Sheng-Dan Nie, Duan-Fang Liao, Jin-Jing Pei, Shan Wang
The abnormally hyperphosphorylated tau is thought to be implicated in diabetes-associated cognitive deficits. The role of mammalian target of rapamycin (mTOR) / S6 kinase (S6K) signalling in the formation of tau hyperphosphorylation has been previously studied. Caveolin-1 (Cav-1), the essential structure protein of caveolae, promotes neuronal survival and growth, and inhibits glucose metabolism. In this study, we aimed to investigate the role of Cav-1 in the formation of tau hyperphosphorylation under chronic hyperglycemic condition (HGC)...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28468941/aberrant-caveolin-1-mediated-smad-signaling-and-proliferation-identified-by-analysis-of-adenine-474-deletion-mutation-c-474dela-in-patient-fibroblasts-a-new-perspective-on-the-mechanism-of-pulmonary-hypertension
#15
Glenn Marsboom, Zhenlong Chen, Yang Yuan, Yanmin Zhang, Chinnaswamy Tiruppathi, James E Loyd, Eric D Austin, Roberto F Machado, Richard D Minshall, Jalees Rehman, Asrar B Malik
A heterozygous caveolin-1 c.474delA mutation has been identified in a family with heritable pulmonary arterial hypertension (PAH). This frameshift mutation leads to a caveolin-1 protein that contains all known functional domains but has a change in only the final 20 amino acids of the C-terminus. Here we studied how this mutation alters caveolin-1 function, using patient-derived fibroblasts. Transmission electron microscopy showed that fibroblasts carrying the c.474delA mutation form typical caveolae. Expression of mutated caveolin-1 in caveolin-1-null mouse fibroblasts failed to induce formation of caveolae due to retention of the mutated protein in the endoplasmic reticulum...
May 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28466393/improved-stability-and-enhanced-oral-bioavailability-of-atorvastatin-loaded-stearic-acid-modified-gelatin-nanoparticles
#16
Deepanshu Shilpi, Varun Kushwah, Ashish Kumar Agrawal, Sanyog Jain
PURPOSE: The present study evaluates the effects of stearic acid conjugation with gelatin and, its pharmaceutical potential to formulate novel atorvastatin (AT) loaded nanoparticles. METHOD: AT loaded stearic acid modified gelatin nanoparticles (AT-MG NPs) were prepared via two-step desolvation method with extensive optimization of different process variables. Further, the developed nanoparticles where evaluated against in vitro Caco-2 cell model and in vivo bioavailability...
May 2, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28462045/on-the-entry-of-an-emerging-arbovirus-into-host-cells-mayaro-virus-takes-the-highway-to-the-cytoplasm-through-fusion-with-early-endosomes-and-caveolae-derived-vesicles
#17
Carlos A M Carvalho, Jerson L Silva, Andréa C Oliveira, Andre M O Gomes
Mayaro virus (MAYV) is an emergent sylvatic alphavirus in South America, related to sporadic outbreaks of a chikungunya-like human febrile illness accompanied by severe arthralgia. Despite its high potential for urban emergence, MAYV is still an obscure virus with scarce information about its infection cycle, including the corresponding early events. Even for prototypical alphaviruses, the cell entry mechanism still has some rough edges to trim: although clathrin-mediated endocytosis is quoted as the putative route, alternative paths as distinct as direct virus genome injection through the cell plasma membrane seems to be possible...
2017: PeerJ
https://www.readbyqxmd.com/read/28461495/inducible-fgf13-ablation-enhances-caveolae-mediated-cardioprotection-during-cardiac-pressure-overload
#18
Eric Q Wei, Daniel S Sinden, Lan Mao, Hailin Zhang, Chuan Wang, Geoffrey S Pitt
The fibroblast growth factor (FGF) homologous factor FGF13, a noncanonical FGF, has been best characterized as a voltage-gated Na(+) channel auxiliary subunit. Other cellular functions have been suggested, but not explored. In inducible, cardiac-specific Fgf13 knockout mice, we found-even in the context of the expected reduction in Na(+) channel current-an unanticipated protection from the maladaptive hypertrophic response to pressure overload. To uncover the underlying mechanisms, we searched for components of the FGF13 interactome in cardiomyocytes and discovered the complete set of the cavin family of caveolar coat proteins...
May 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28433630/loss-of-murc-cavin-4-induces-jnk-and-mmp-9-activity-enhancement-in-vascular-smooth-muscle-cells-and-exacerbates-abdominal-aortic-aneurysm
#19
Kotaro Miyagawa, Takehiro Ogata, Tomomi Ueyama, Takeru Kasahara, Naohiko Nakanishi, Daisuke Naito, Takuya Taniguchi, Tetsuro Hamaoka, Naoki Maruyama, Masahiro Nishi, Taizo Kimura, Hiroyuki Yamada, Hiroki Aoki, Satoaki Matoba
Abdominal aortic aneurysm (AAA) is relatively common in elderly patients with atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal muscle cells and smooth muscle cells. Here, we show a novel functional role of MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and AAA development. Both wild-type (WT) and MURC/Cavin-4 knockout (MURC(-/-)) mice subjected to periaortic application of CaCl2 developed AAAs...
April 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28432017/dual-functional-nanoparticles-for-precise-drug-delivery-to-alzheimer-s-disease-lesions-targeting-mechanisms-pharmacodynamics-and-safety
#20
Xiaoyao Zheng, Chi Zhang, Qian Guo, Xu Wan, Xiayan Shao, Qingfeng Liu, Qizhi Zhang
Alzheimer's disease (AD) is the most common form of dementia and is characterized by the cerebral accumulation of extracellular amyloid plaques. In a previous study, this histopathological hallmark was used as a target on a dual-functional nanoparticle (TQNP) to deliver biotechnological drugs, such as the H102 peptide, a β-sheet breaker, to AD lesions precisely. This delivery system could reduce the amyloid-β (Aβ) burden in the brains of AD model mice, as well as ameliorated the memory impairment of the mice...
April 18, 2017: International Journal of Pharmaceutics
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