scholarly journals Effects of Cholesterol in Stress-Related Neuronal Death—A Statistical Analysis Perspective

2020 ◽  
Vol 21 (8) ◽  
pp. 2905
Author(s):  
Maher A. Dayeh ◽  
George Livadiotis ◽  
Farzan Aminian ◽  
Kwan H. Cheng ◽  
James L. Roberts ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Statistical Analysis ◽  
Plasma Cholesterol ◽  
Intact Cells ◽  
Cholesterol Levels ◽  
Detailed Statistical Analysis ◽  
Gompertz Law ◽  
A Minor ◽  
The Relationship ◽  
Plasma Membrane Cholesterol

The association between plasma cholesterol levels and the development of dementia continues to be an important topic of discussion in the scientific community, while the results in the literature vary significantly. We study the effect of reducing oxidized neuronal cholesterol on the lipid raft structure of plasma membrane. The levels of plasma membrane cholesterol were reduced by treating the intact cells with methyl-ß-cyclodextrin (MßCD). The relationship between the cell viability with varying levels of MßCD was then examined. The viability curves are well described by a modified form of the empirical Gompertz law of mortality. A detailed statistical analysis is performed on the fitting results, showing that increasing MßCD concentration has a minor, rather than significant, effect on the cellular viability. In particular, the dependence of viability on MßCD concentration was found to be characterized by a ~25% increase per 1 μM of MßCD concentration.

scholarly journals Three pools of plasma membrane cholesterol and their relation to cholesterol homeostasis

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Akash Das ◽  
Michael S Brown ◽  
Donald D Anderson ◽  
Joseph L Goldstein ◽  
Arun Radhakrishnan
Keyword(s):  
Plasma Membrane ◽  
Regulatory Mechanism ◽  
Low Density Lipoprotein ◽  
Human Fibroblasts ◽  
Density Lipoprotein ◽  
Cholesterol Homeostasis ◽  
Mutant Form ◽  
Perfringolysin O ◽  
Cholesterol Levels ◽  
Plasma Membrane Cholesterol

When human fibroblasts take up plasma low density lipoprotein (LDL), its cholesterol is liberated in lysosomes and eventually reaches the endoplasmic reticulum (ER) where it inhibits cholesterol synthesis by blocking activation of SREBPs. This feedback protects against cholesterol overaccumulation in the plasma membrane (PM). But how does ER know whether PM is saturated with cholesterol? In this study, we define three pools of PM cholesterol: (1) a pool accessible to bind 125I-PFO*, a mutant form of bacterial Perfringolysin O, which binds cholesterol in membranes; (2) a sphingomyelin(SM)-sequestered pool that binds 125I-PFO* only after SM is destroyed by sphingomyelinase; and (3) a residual pool that does not bind 125I-PFO* even after sphingomyelinase treatment. When LDL-derived cholesterol leaves lysosomes, it expands PM's PFO-accessible pool and, after a short lag, it also increases the ER's PFO-accessible regulatory pool. This regulatory mechanism allows cells to ensure optimal cholesterol levels in PM while avoiding cholesterol overaccumulation.

Cholesterol distribution in rat heart myocytes

1995 ◽  
Vol 268 (2) ◽  
pp. H759-H766
Author(s):  
H. Shmeeda ◽  
D. Petkova ◽  
Y. Barenholz
Keyword(s):  
Plasma Membrane ◽  
Rat Heart ◽  
Cholesterol Oxidase ◽  
Neonatal Rat ◽  
Relative Distribution ◽  
Intact Cells ◽  
Cholesterol Levels ◽  
Rat Heart Myocytes ◽  
Small Unilamellar Vesicles ◽  
Cholesterol Monohydrate

Cholesterol oxidase was used to investigate the distribution of free cholesterol between plasma membrane and intracellular pools in cultured neonatal rat heart myocytes. Only 20% of the total unesterified cholesterol was converted to delta 4-cholestenone by cholesterol oxidase in intact cells. With increasing age in culture and concurrent hypertrophy, there was an increase in unesterified cellular cholesterol and plasma membrane cholesterol; their relative distribution remained unchanged. Electron micrographs of negatively stained samples of day 4 cytosol revealed the presence of vesicles 50–200 nm in diameter. Cholesterol monohydrate crystals were found in the cytosol of hypertrophic day 14 cells. Treatment of day 14 cells with small unilamellar vesicles of egg phosphatidylcholine reduced plasma membrane and intracellular cholesterol levels, resulting in the disappearance of the cholesterol monohydrate crystals and the formation of vesicles smaller than those observed in day 4 cultures.

scholarly journals Distribution of membrane cholesterol of adrenal cortical cells after corticotropin stimulation

1983 ◽  
Vol 214 (2) ◽  
pp. 561-567 ◽  
Author(s):  
O M Conneely ◽  
J M Greene ◽  
D R Headon ◽  
J Hsiao ◽  
F Ungar
Keyword(s):  
Plasma Membrane ◽  
Cholesteryl Ester ◽  
Membrane Cholesterol ◽  
Cortical Cells ◽  
Cholesterol Levels ◽  
Adrenal Cortical Cells ◽  
Hydrolysis Of ◽  
Plasma Membrane Cholesterol ◽  
Corticotropin Stimulation ◽  
Stimulation Of

Membrane cholesterol in adrenal cortical cells is enriched in the plasma membrane. Stimulation of isolated adrenal cortical cells with corticotropin leads to the production of corticosterone. At high levels of corticotropin, cholesterol for corticosterone synthesis arises by hydrolysis of cellular cholesteryl ester, whereas at lower levels of corticotropin cholesteryl ester levels are unchanged from control values and there is a decrease in plasma-membrane cholesterol levels.

Abstract 201: Maternal HDL-Cholesterol Levels in Women From the Gambia are Directly Related to Infant Birthweight

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Sandra L Rebholz ◽  
John T Melchior ◽  
Jeff Welge ◽  
Andrew M Prentice ◽  
Sophie E Moore ◽  
...  
Keyword(s):  
Fetal Growth ◽  
Growth Rates ◽  
Low Birthweight ◽  
Plasma Cholesterol ◽  
Hdl Cholesterol ◽  
Term Infants ◽  
Placental Function ◽  
Cholesterol Levels ◽  
Potential Biomarker ◽  
The Relationship

Babies born with low birthweight are often at a health disadvantage. Previous studies have shown direct relationships between maternal plasma cholesterol and infant birthweight in resource-rich countries. As plasma cholesterol levels are often decreased in resource-poor countries, the purpose of these studies was to evaluate the relationship between plasma cholesterol and birthweight in women enrolled in the ENID trial (ISRCTN49285450) in rural Gambia, West Africa. Plasma was obtained at enrolment (13.6±3.3 wk) and at 20 and 30 weeks of gestation; samples were obtained from women with term infants that weighed <2.75 kg or >3.25 kg at birth. Women with lower HDL-cholesterol (HDL-C) concentrations in mid-pregnancy had lower birthweight infants compared to women with higher HDL-C concentrations. There was no significant association between LDL-C or total cholesterol concentrations and birthweight. The relationship with HDL-C and birthweight was maintained when maternal BMI was included in the model. To begin to elucidate the processes involved in the regulation of fetal growth, placental function was examined in mice with increasing maternal HDL-C concentrations based on apoA-I levels; mice were lacking apoA-I (apoA-I -/- ), were wildtype (apoA-I +/+ ), or had excess apoA-I (apoA-I tg/tg ). HDL decreased in size as plasma apoA-I levels increased, and there were no statistical differences in the proteins carried by HDL, except for apoA-I, in pregnant mice of different genotypes. However, pregnancy alone led to changes in the HDL proteome. Importantly, fetuses of mice with lower concentrations of maternal HDL-C had reduced growth rates, not due to a lack of fetal apoA-I. The murine fetal growth rates were directly related to nutrient uptake by and transport across the placenta. This work suggests that maternal HDL affects placental function leading to enhanced nutrient supply and improved growth in utero, making HDL a potential biomarker for fetal growth and putative target for intervention.

scholarly journals Defining the subcellular distribution and metabolic channeling of phosphatidylinositol

2020 ◽  
Vol 219 (3) ◽  
Author(s):  
Joshua G. Pemberton ◽  
Yeun Ju Kim ◽  
Jana Humpolickova ◽  
Andrea Eisenreichova ◽  
Nivedita Sengupta ◽  
...  
Keyword(s):  
Golgi Complex ◽  
Kinetic Studies ◽  
Intact Cells ◽  
Metabolic Channeling ◽  
Bacterial Enzyme ◽  
Common Precursor ◽  
Steady State Levels ◽  
The Common ◽  
A Minor ◽  
The Relationship

Phosphatidylinositol (PI) is an essential structural component of eukaryotic membranes that also serves as the common precursor for polyphosphoinositide (PPIn) lipids. Despite the recognized importance of PPIn species for signal transduction and membrane homeostasis, there is still a limited understanding of the relationship between PI availability and the turnover of subcellular PPIn pools. To address these shortcomings, we established a molecular toolbox for investigations of PI distribution within intact cells by exploiting the properties of a bacterial enzyme, PI-specific PLC (PI-PLC). Using these tools, we find a minor presence of PI in membranes of the ER, as well as a general enrichment within the cytosolic leaflets of the Golgi complex, peroxisomes, and outer mitochondrial membrane, but only detect very low steady-state levels of PI within the plasma membrane (PM) and endosomes. Kinetic studies also demonstrate the requirement for sustained PI supply from the ER for the maintenance of monophosphorylated PPIn species within the PM, Golgi complex, and endosomal compartments.

scholarly journals The relationship between pertussis-toxin-induced ADP-ribosylation of a plasma-membrane protein and reversal of muscarinic inhibition of prolactin secretion in GH3 cells

1984 ◽  
Vol 224 (1) ◽  
pp. 339-342 ◽  
Author(s):  
R J Wojcikiewicz ◽  
P R Dobson ◽  
L I Irons ◽  
A Robinson ◽  
B L Brown
Keyword(s):  
Plasma Membrane ◽  
Pertussis Toxin ◽  
Protein A ◽  
Prolactin Secretion ◽  
Gh3 Cells ◽  
Intact Cells ◽  
Adp Ribosylation ◽  
Cell Plasma ◽  
The Relationship ◽  
Gh3 Cell

Pertussis toxin (PT) caused the ADP-ribosylation of a Mr-41 000 protein in GH3-cell plasma-membrane preparations. This effect, and muscarinic inhibition of prolactin release, were reversed at similar rates by pretreatment of intact cells with PT. These results suggest that the Mr-41 000 protein is modified in intact GH3 cells, and that this protein (a component of the putative Ni unit of adenylate cyclase) is involved in the expression of muscarinic inhibition.

scholarly journals Shear stress activates mitochondrial oxidative phosphorylation by reducing plasma membrane cholesterol in vascular endothelial cells

2020 ◽  
Vol 117 (52) ◽  
pp. 33660-33667
Author(s):  
Kimiko Yamamoto ◽  
Yoshitsugu Nogimori ◽  
Hiromi Imamura ◽  
Joji Ando
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Plasma Membrane ◽  
Vascular Endothelial Cells ◽  
Membrane Cholesterol ◽  
Vascular Endothelial ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Atp Production ◽  
Cholesterol Levels ◽  
Plasma Membrane Cholesterol

Vascular endothelial cells (ECs) sense and respond to hemodynamic shear stress, which is critical for circulatory homeostasis and the pathophysiology of vascular diseases. The mechanisms of shear stress mechanotransduction, however, remain elusive. We previously demonstrated a direct role of mitochondria in the purinergic signaling of shear stress: shear stress increases mitochondrial adenosine triphosphate (ATP) production, triggering ATP release and Ca2+ signaling via EC purinoceptors. Here, we showed that shear stress rapidly decreases cholesterol in the plasma membrane, thereby activating mitochondrial ATP production. Imaging using domain 4 mutant-derived cholesterol biosensors showed that the application of shear stress to cultured ECs markedly decreased cholesterol levels in both the outer and inner plasma membrane bilayers. Flow cytometry showed that the cholesterol levels in the outer bilayer decreased rapidly after the onset of shear stress, reached a minimum (around 60% of the control level) at 10 min, and plateaued thereafter. After the shear stress ceased, the decreased cholesterol levels returned to those seen in the control. A biochemical analysis showed that shear stress caused both the efflux and the internalization of plasma membrane cholesterol. ATP biosensor imaging demonstrated that shear stress significantly increased mitochondrial ATP production. Similarly, the treatment of cells with methyl-β-cyclodextrin (MβCD), a membrane cholesterol-depleting agent, increased mitochondrial ATP production. The addition of cholesterol to cells inhibited the increasing effects of both shear stress and MβCD on mitochondrial ATP production in a dose-dependent manner. These findings indicate that plasma membrane cholesterol dynamics are closely coupled to mitochondrial oxidative phosphorylation in ECs.

Sign in / Sign up

Export Citation Format

Share Document