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Methyl cyclodextrin and caveolae

Wating Su, Yuan Zhang, Qiongxia Zhang, Jinjin Xu, Liying Zhan, Qiqi Zhu, Qingquan Lian, Huimin Liu, Zhong-Yuan Xia, Zhengyuan Xia, Shaoqing Lei
BACKGROUND: Patients with diabetes are prone to develop cardiac hypertrophy and more susceptible to myocardial ischemia-reperfusion (I/R) injury, which are concomitant with hyperglycemia-induced oxidative stress and impaired endothelial nitric oxide (NO) synthase (eNOS)/NO signaling. Caveolae are critical in the transduction of eNOS/NO signaling in cardiovascular system. Caveolin (Cav)-3, the cardiomyocytes-specific caveolae structural protein, is decreased in the diabetic heart in which production of reactive oxygen species are increased...
October 12, 2016: Cardiovascular Diabetology
Mohammed Z Haque, Victoria J McIntosh, Abdul B Abou Samra, Ramzi M Mohammad, Robert D Lasley
UNLABELLED: Membrane cholesterol levels play an important factor in regulating cell function. Sarcolemmal cholesterol is concentrated in lipid rafts and caveolae, which are flask-shaped invaginations of the plasma membrane. The scaffolding protein caveolin permits the enrichment of cholesterol in caveolae, and caveolin interactions with numerous proteins regulate their function. The purpose of this study was to determine whether acute reductions in cardiomyocyte cholesterol levels alter subcellular protein kinase activation, intracellular Ca2+ and contractility...
2016: PloS One
Hai-Xia Jiao, Yun-Ping Mu, Long-Xin Gui, Fu-Rong Yan, Da-Cen Lin, James S K Sham, Mo-Jun Lin
Caveolin-1 (Cav-1) is a major component protein associated with caveolae in the plasma membrane and has been identified as a regulator of store-operated Ca(2+) entry (SOCE) and receptor-operated Ca(2+) entry (ROCE). However, the contributions of caveolae/Cav-1 of pulmonary arterial smooth muscle cells (PASMCs) to the altered Ca(2+) signaling pathways in pulmonary arteries (PAs) during pulmonary hypertension (PH) have not been fully characterized. The present study quantified caveolae number and Cav-1 expression, and determined the effects of caveolae disruption on ET-1, cyclopiazonic acid (CPA) and 1-Oleoyl-2-acetyl-glycerol (OAG)-induced contraction in PAs and Ca(2+) influx in PASMCs of chronic hypoxia (CH)- and monocrotaline (MCT)-induced PH rats...
September 2016: Vascular Pharmacology
Guillaume Gilbert, Thomas Ducret, Jean-Pierre Savineau, Roger Marthan, Jean-François Quignard
Caveolae are stiff plasma membrane microdomains implicated in various cell response mechanisms like Ca(2+) signaling and mechanotransduction. Pulmonary arterial smooth muscle cells (PASMC) transduce mechanical stimuli into Ca(2+) increase via plasma membrane stretch-activated channels (SAC). This mechanotransduction process is modified in pulmonary hypertension (PH) during which stretch forces are increased by the increase in arterial blood pressure. We propose to investigate how caveolae are involved in the pathophysiology of PH and particularly in mechanotransduction...
June 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Hong Yang, Liuyuan Guan, Shun Li, Ying Jiang, Niya Xiong, Li Li, Chunhui Wu, Hongjuan Zeng, Yiyao Liu
Cancer cells are subjected to fluid shear stress during passage through the venous and lymphatic system. Caveolin-1 (Cav-1), a principal structural component of caveolar membrane domains, contributes to cancer development but its mechanobiological roles under low shear stress (LSS) conditions remain largely unknown. Here, we identified Cav-1 is mechanosensitive to LSS exposure, and its activation-induced PI3K/Akt/mTOR signaling promotes motility, invadopodia formation and metastasis of breast carcinoma MDA-MB-231 cells...
March 29, 2016: Oncotarget
Ming Yan, Yun Zhang, Haiyan Qin, Kezhou Liu, Miao Guo, Yakun Ge, Mingen Xu, Yonghong Sun, Xiaoxiang Zheng
Cadmium telluride quantum dots (CdTe QDs) have been proposed to induce oxidative stress, which plays a crucial role in CdTe QDs-mediated mitochondrial-dependent apoptosis in human umbilical vein endothelial cells (HUVECs). However, the direct interactions of CdTe QDs with HUVECs and their potential impairment of other organelles like endoplasmic reticulum (ER) in HUVECs are poorly understood. In this study, we reported that the negatively charged CdTe QDs (-21.63±0.91 mV), with good dispersity and fluorescence stability, were rapidly internalized via endocytosis by HUVECs, as the notable internalization could be inhibited up to 95...
2016: International Journal of Nanomedicine
Jian He, Yi-Wen Zheng, Yi-Fan Lin, Shu Mi, Xiao-Wei Qin, Shao-Ping Weng, Jian-Guo He, Chang-Jun Guo
Caveolae are flask-shaped invaginations of the plasma membrane. Caveolae play important roles in the process of viruses entry into host cells, but the roles of caveolae at the late stage of virus infection were not completely understood. Tiger frog virus (TFV) has been isolated from the diseased tadpoles of the frog, Rana tigrina rugulosa, and causes high mortality of tiger frog tadpoles cultured in Southern China. In the present study, the roles of caveolae at the late stage of TFV infection were investigated...
2016: Scientific Reports
Natasha Baker, Jihee Sohn, Rocky S Tuan
INTRODUCTION: Stem cells are considered an important resource for tissue repair and regeneration. Their utilization in regenerative medicine will be aided by mechanistic insight into their responsiveness to external stimuli. It is likely that, similar to all other cells, an initial determinant of stem cell responsiveness to external stimuli is the organization of signaling molecules in cell membrane rafts. The clustering of signaling molecules in these cholesterol-rich membrane microdomains can affect the activity, specificity, cross-talk and amplification of cell signaling...
December 1, 2015: Stem Cell Research & Therapy
Alexey V Glukhov, Marina Balycheva, Jose L Sanchez-Alonso, Zeki Ilkan, Anita Alvarez-Laviada, Navneet Bhogal, Ivan Diakonov, Sophie Schobesberger, Markus B Sikkel, Anamika Bhargava, Giuseppe Faggian, Prakash P Punjabi, Steven R Houser, Julia Gorelik
BACKGROUND: Distinct subpopulations of L-type calcium channels (LTCCs) with different functional properties exist in cardiomyocytes. Disruption of cellular structure may affect LTCC in a microdomain-specific manner and contribute to the pathophysiology of cardiac diseases, especially in cells lacking organized transverse tubules (T-tubules) such as atrial myocytes (AMs). METHODS AND RESULTS: Isolated rat and human AMs were characterized by scanning ion conductance, confocal, and electron microscopy...
December 22, 2015: Circulation
Qi-Qi Zhang, Liang Huang, Chao Han, Xin Guan, Ya-Jun Wang, Jing Liu, Jing-Hua Wan, Wei Zou
Recent evidence suggests that caveolin-1 (Cav-1), the major protein constituent of caveolae, plays a prominent role in neuronal nutritional availability with cellular fate regulation besides in several cellular processes such as cholesterol homeostasis, regulation of signal transduction, integrin signaling and cell growth. Here, we aimed to investigate the function of Cav-1 and glucose transporter 4 (GLUT4) upon glucose deprivation (GD) in PC12 cells. The results demonstrated firstly that both Cav-1 and GLUT4 were up-regulated by glucose withdrawal in PC12 cells by using Western blot and laser confocal technology...
August 25, 2015: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Masato Tamura, Mitsuoki Kawano, Mari Sato, Masayuki Nashimoto
tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing) is an RNA-mediated gene expression control technology with therapeutic potential. Recently, our group demonstrated that a heptamer, mh1 (Bcl‑2), targeting human Bcl-2 mRNA, can be taken up by cells without the use of any transfection reagents and can induce the apoptosis of leukemia cells. However, little is known regarding the mechanism of naked small guide (sg)RNA uptake by cultured cells. Therefore, in the present study the effects of various inhibitors on the induction of apoptosis by naked sgRNA treatment were investigated in order to identify the uptake pathway required for sgRNA function in cultured cells...
October 2015: Molecular Medicine Reports
Shuai Wang, Mari T Kaartinen
Transglutaminases (TGs) are a family of widely distributed enzymes that catalyze protein crosslinking by forming a covalent isopeptide bond between the substrate proteins. We have shown that MC3T3-E1 osteoblasts express Factor XIII-A (FXIII-A), and that the extracellular crosslinking activity of FXIII-A is involved in regulating matrix secretion and deposition. In this study, we have investigated the localization and potential role of intracellular FXIII-A. Conventional immunofluorescence microscopy and TIRF microscopy analyses showed that FXIII-A co-localizes with caveolin-1 in specialized membrane structures, caveolae, in differentiating osteoblasts...
November 2015: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
A Folino, A E Sprio, F Di Scipio, G N Berta, R Rastaldo
We investigated the effect of α-linolenic acid (ALA) in protecting the heart from injury caused by β-adrenergic overstimulation. ALA's role either in isoproterenol (ISO)-treated isolated rat cardiomyocytes (H9c2 cells) or in in vivo rat hearts was studied. In isolated cardiomyocytes in vitro, the involvement of kinases (Src and PI3K) in protection was tested using the specific inhibitors (PP2 or LY294002 respectively), while the role of caveolae was assessed by their disruption with methyl-β-cyclodextrin...
July 2015: Food & Function
A Y Al-Brakati, T Kamishima, C Dart, J M Quayle
Background and Purpose. Caveolae act as signalling hubs in endothelial and smooth muscle cells. Caveolar disruption by the membrane cholesterol depleting agent methyl-β-cyclodextrin (M-β-CD) has various functional effects on arteries including (i) impairment of endothelium-dependent relaxation, and (ii) alteration of smooth muscle cell (SMC) contraction independently of the endothelium. The aim of this study was to explore the effects of M-β-CD on rat femoral arteries. Methods. Isometric force was measured in rat femoral arteries stimulated to contract with a solution containing 20 mM K(+) and 200 nM Bay K 8644 (20 K/Bay K) or with one containing 80 mM K(+)(80 K)...
2015: PeerJ
Dong Zhang, Xiaolei Pan, Shang Wang, Yinglei Zhai, Jibin Guan, Qiang Fu, Xiaoli Hao, Wanpeng Qi, Yingli Wang, He Lian, Xiaohong Liu, Yongjun Wang, Yinghua Sun, Zhonggui He, Jin Sun
In order to improve oral bioavailability of tacrolimus (FK506), a novel poly(methyl vinyl ether-co-maleic anhydride)-graft-hydroxypropyl-β-cyclodextrin amphiphilic copolymer (CD-PVM/MA) is developed, combining the bioadhesiveness of PVM/MA, P-glycoprotein (P-gp), and cytochrome P450-inhibitory effect of CD into one. The FK506-loaded nanoparticles (CD-PVM/MA-NPs) were obtained by solvent evaporation method. The physiochemical properties and intestinal absorption mechanism of FK506-loaded CD-PVM/MA-NPs were characterized, and the pharmacokinetic behavior was investigated in rats...
July 6, 2015: Molecular Pharmaceutics
Ilari Pulli, Tomas Blom, Christoffer Löf, Melissa Magnusson, Alessandro Rimessi, Paolo Pinton, Kid Törnquist
Caveolae are plasma membrane invaginations enriched in sterols and sphingolipids. Sphingosine kinase 1 (SK1) is an oncogenic protein that converts sphingosine to sphingosine 1-phosphate (S1P), which is a messenger molecule involved in calcium signaling. Caveolae contain calcium responsive proteins, but the effects of SK1 or S1P on caveolar calcium signaling have not been investigated. We generated a Caveolin-1-Aequorin fusion protein (Cav1-Aeq) that can be employed for monitoring the local calcium concentration at the caveolae ([Ca²⁺]cav)...
September 2015: Biochimica et Biophysica Acta
Jennifer L Brignell, Matthew D Perry, Carl P Nelson, Jonathon M Willets, R A John Challiss, Noel W Davies
Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells...
2015: PloS One
Yuantao Liu, Shengxia Lu, Yuchao Zhang, Xiangdong Wang, Feng Kong, Ye Liu, Li Peng, Yuqin Fu
Accumulation of extracellular matrix (ECM) in glomerular mesangium correlates with loss of renal function in diabetic nephropathy. However, the mechanisms underlying are still incompletely known. In the present study, we explored the role of caveolae in ECM production in rat mesangial cells (MCs) stimulated by high glucose or transforming growth factor-β1 (TGF-β1), and investigated the possible mechanisms. High glucose (HG) or TGF-β1 significantly increased collagen-1 and fibronectin expression at both mRNA and protein levels in time- course dependent manners, and simultaneously induced caveolin-1 tyrosine phosphorylation...
2014: International Journal of Clinical and Experimental Pathology
Astrid Rohrbeck, Leonie von Elsner, Sandra Hagemann, Ingo Just
The Clostridium botulinum C3 exoenzyme selectively ADP-ribosylates low molecular weight GTP-binding proteins RhoA, B and C. This covalent modification inhibits Rho signaling activity, resulting in distinct actin cytoskeleton changes. Although C3 exoenzyme has no binding, the translocation domain assures that C3 enters cells and acts intracellularly. C3 uptake is thought to occur due to the high concentration of the C3 enzyme. However, recent work indicates that C3 is selectively endocytosed, suggesting a specific endocytotic pathway, which is not yet understood...
February 2015: Toxins
Takahito Moriyama, Takashi Takei, Mitsuyo Itabashi, Keiko Uchida, Ken Tsuchiya, Kosaku Nitta
Caveolae on human renal glomerular endothelial cells (HRGECs) are increased in glomerular disease and correlate with the degree of albuminuria. To assess the mechanism by which caveolae contribute to albuminuria, we investigated whether albumin enters into HRGECs through caveolae. HRGECs were incubated with Alexa Fluor 488 labeled BSA or transferrin, followed by immunofluorescence localization with antibody to caveolin-1 (Cav-1), the main structural protein of caveolae, or clathrin, the major structural protein of clathrin coated pits, to assess whether BSA colocalized with Cav-1...
June 2015: Journal of Cellular Biochemistry
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