scholarly journals Condensing Effect of Cholesterol on hBest1/POPC and hBest1/SM Langmuir Monolayers

Membranes ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 52
Author(s):  
Pavel Videv ◽  
Nikola Mladenov ◽  
Tonya Andreeva ◽  
Kirilka Mladenova ◽  
Veselina Moskova-Doumanova ◽  
...  

Human bestrophin-1 protein (hBest1) is a transmembrane channel associated with the calcium-dependent transport of chloride ions in the retinal pigment epithelium as well as with the transport of glutamate and GABA in nerve cells. Interactions between hBest1, sphingomyelins, phosphatidylcholines and cholesterol are crucial for hBest1 association with cell membrane domains and its biological functions. As cholesterol plays a key role in the formation of lipid rafts, motional ordering of lipids and modeling/remodeling of the lateral membrane structure, we examined the effect of different cholesterol concentrations on the surface tension of hBest1/POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and hBest1/SM Langmuir monolayers in the presence/absence of Ca2+ ions using surface pressure measurements and Brewster angle microscopy studies. Here, we report that cholesterol: (1) has negligible condensing effect on pure hBest1 monolayers detected mainly in the presence of Ca2+ ions, and; (2) induces a condensing effect on composite hBest1/POPC and hBest1/SM monolayers. These results offer evidence for the significance of intermolecular protein–lipid interactions for the conformational dynamics of hBest1 and its biological functions as multimeric ion channel.

Author(s):  
P.J. Lea ◽  
M.J. Hollenberg

Our current understanding of mitochondrial ultrastructure has been derived primarily from thin sections using transmission electron microscopy (TEM). This information has been extrapolated into three dimensions by artist's impressions (1) or serial sectioning techniques in combination with computer processing (2). The resolution of serial reconstruction methods is limited by section thickness whereas artist's impressions have obvious disadvantages.In contrast, the new techniques of HRSEM used in this study (3) offer the opportunity to view simultaneously both the internal and external structure of mitochondria directly in three dimensions and in detail.The tridimensional ultrastructure of mitochondria from rat hepatocytes, retinal (retinal pigment epithelium), renal (proximal convoluted tubule) and adrenal cortex cells were studied by HRSEM. The specimens were prepared by aldehyde-osmium fixation in combination with freeze cleavage followed by partial extraction of cytosol with a weak solution of osmium tetroxide (4). The specimens were examined with a Hitachi S-570 scanning electron microscope, resolution better than 30 nm, where the secondary electron detector is located in the column directly above the specimen inserted within the objective lens.


Author(s):  
Kazushige Hirosawa ◽  
Eichi Yamada

The pigment epithelium is located between the choriocapillary and the visual cells. The pigment epithelial cell is characterized by a large amount of the smooth endoplasmic reticulum (SER) in its cytoplasm. In addition, the pigment epithelial cell of some lower vertebrate has myeloid body as a specialized form of the SER. Generally, SER is supposed to work in the lipid metabolism. However, the functions of abundant SER and myeloid body in the pigment epithelial cell are still in question. This paper reports an attempt, to depict the functions of these organelles in the frog retina by administering one of phospholipid precursors.


Author(s):  
G.E. Korte ◽  
M. Marko ◽  
G. Hageman

Sodium iodate iv. damages the retinal pigment epithelium (RPE) in rabbits. Where RPE does not regenerate (e.g., 1,2) Muller glial cells (MC) forma subretinal scar that replaces RPE. The MC response was studied by HVEM in 3D computer reconstructions of serial thick sections, made using the STEREC0N program (3), and the HVEM at the NYS Dept. of Health in Albany, NY. Tissue was processed for HVEM or immunofluorescence localization of a monoclonal antibody recognizing MG microvilli (4).


Author(s):  
Beth Burnside

The vertebrate photoreceptor provides a drammatic example of cell polarization. Specialized to carry out phototransduction at its distal end and to synapse with retinal interneurons at its proximal end, this long slender cell has a uniquely polarized morphology which is reflected in a similarly polarized cytoskeleton. Membranes bearing photopigment are localized in the outer segment, a modified sensory cilium. Sodium pumps which maintain the dark current critical to photosensory transduction are anchored along the inner segment plasma membrane between the outer segment and the nucleus.Proximal to the nucleus is a slender axon terminating in specialized invaginating synapses with other neurons of the retina. Though photoreceptor diameter is only 3-8u, its length from the tip of the outer segment to the synapse may be as great as 200μ. This peculiar linear cell morphology poses special logistical problems and has evoked interesting solutions for numerous cell functions. For example, the outer segment membranes turn over by means of a unique mechanism in which new disks are continuously added at the proximal base of the outer segment, while effete disks are discarded at the tip and phagocytosed by the retinal pigment epithelium. Outer segment proteins are synthesized in the Golgi near the nucleus and must be transported north through the inner segment to their sites of assembly into the outer segment, while synaptic proteins must be transported south through the axon to the synapse.The role of the cytoskeleton in photoreceptor motile processes is being intensely investigated in several laboratories.


2017 ◽  
Vol 26 (2) ◽  
pp. 157-163 ◽  
Author(s):  
Lakshmi Manogna Chintalacheruvu ◽  
Trudy Shaw ◽  
Avanija Buddam ◽  
Osama Diab ◽  
Thamer Kassim ◽  
...  

Gastrointestinal cancer is one of the major causes of death worldwide. Hereditary gastrointestinal cancer syndromes constitute about 5-10% of all cancers. About 20-25% of undiagnosed cases have a possible hereditary component, which is not yet established. In the last few decades, the advance in genomics has led to the discovery of multiple cancer predisposition genes in gastrointestinal cancer. Physicians should be aware of these syndromes to identify high-risk patients and offer genetic testing to prevent cancer death. In this review, we describe clinical manifestations, genetic testing and its challenges, diagnosis and management of the major hereditary gastrointestinal cancer syndromes.Key words:  −  −  −  − .Abbreviations: ACG: American College of Gastroenterology; AFAP: attenuated FAP; APC: adenomatous polyposis coli; CDH1: E-cadherin; CHRPE: congenital hypertrophy of the retinal pigment epithelium; CRC: colorectal cancer; FAMMM: Familial atypical multiple mole melanoma; FAP: Familial adenomatous polyposis; GC: gastric cancer; HDGC: Hereditary diffuse gastric cancer; IHC: immunohistochemical; IPAA: ileal pouch–anal anastomosis; IRA: ileorectal anastomosis; MSI: microsatellite instability; MMR: mismatch repair; miRNA: micro RNA.


2018 ◽  
Vol 25 (13) ◽  
pp. 1480-1500 ◽  
Author(s):  
Sho-ichi Yamagishi ◽  
Takanori Matsui

Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors, serpins. It was first identified as a neuronal differentiating factor secreted by human retinal pigment epithelial cells, and then found to be the most potent inhibitor of pathological angiogenesis in mammalian eyes. Recently, PEDF has been shown not only to suppress oxidative stress and inflammatory reactions in vascular wall cells, T cells and macrophages, and adipocytes, but also to exert antithrombotic and anti-fibrotic properties, thereby protecting against the development and progression of various cardiometabolic diseases and related complications. Furthermore, accumulating evidence has suggested that circulating PEDF levels may be a biomarker of severity and prognosis of these devastating disorders. Number of subjects with visceral obesity and insulin resistance is increasing, and the metabolic syndrome and its related complications, such as diabetes, nonalcoholic fatty liver disease/non-alcoholic steatohepatits, and atherosclerotic cardiovascular disease are a growing health challenge. Therefore, in this study, we review the pathophysiological role of PEDF in obesity and metabolic disorders, cardiovascular disease, diabetic eye and kidney complications, liver diseases, and reproductive system disorders, and discuss the potential clinical utility of modulating the expression and actions of PEDF for preventing these cardiometabolic disorders. We also refer to the clinical value of PEDF as a biomarker in cardiometabolic complications.


2019 ◽  
Vol 16 (3) ◽  
pp. 258-265
Author(s):  
Kei Takahashi ◽  
Tomomi Masuda ◽  
Mitsunori Harada ◽  
Tadashi Inoue ◽  
Shinsuke Nakamura ◽  
...  

Objective: This study aimed to examine whether DC101 (anti-VEGFR2 antibody)- modified micelles have applications as novel drug delivery devices, which allow small molecule antiangiogenic agents to deliver to angiogenic sites on a murine laser-induced choroidal neovascularization (CNV) model. Materials and Method: CNV was induced by photocoagulation on the unilateral eye of each mouse under anesthesia. Immediately after laser coagulation, E7974-loaded DC101-modified micelles and motesanib-loaded DC101-modified micelles were intravitreally administrated. Two weeks after photocoagulation, CNV was visualized using fluorescein-conjugated dextran (MW=2,000 kDa), and the CNV area was measured in retinal pigment epithelium (RPE)-choroidal flat mounts. Results: Intravitreal administration of both DC101-modified micelles loaded with E7974 at 2 µM and motesanib at 2 µM significantly reduced CNV area in the murine laser-induced CNV model at a clearly lower concentration than the effective dose of each agent. Conclusion: These results suggest that DC101-modified micelle might be effective drug carrier system for treating CNV and other ocular angiogenic diseases.


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