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Related Concept Videos

Nitric Oxide Signaling Pathway01:28

Nitric Oxide Signaling Pathway

Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...
Membrane Fluidity01:23

Membrane Fluidity

Cell membranes are composed of phospholipids, proteins, and carbohydrates loosely attached to one another through chemical interactions. Molecules are generally able to move about in the plane of the membrane, giving the membrane its flexible nature called fluidity. Two other features of the membrane contribute to membrane fluidity: the chemical structure of the phospholipids and the presence of cholesterol in the membrane.Fatty acids tails of phospholipids can be either saturated or...
Membrane Fluidity01:26

Membrane Fluidity

Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is a relatively...
Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
Types of Signaling Molecules01:32

Types of Signaling Molecules

In multicellular organisms, many molecules transmit signals between cells to pass information. These signals vary in complexity and include small peptides, nucleotides, steroids, fatty acid derivatives, and dissolved gases such as nitric oxide. Some signaling molecules diffuse through the plasma membrane to act locally between neighboring cells or travel long distances. Others remain attached to the cell surface, transmitting information to other cells only when they make contact. In some...
Asymmetric Lipid Bilayer01:35

Asymmetric Lipid Bilayer

Biological membranes show uneven distribution of different types of lipids in the inner and outer layers, resulting in transverse asymmetric membranes. The treatment of the erythrocyte membrane with the enzyme phospholipase confirmed the asymmetric nature of the lipid bilayer. The enzyme hydrolyzes lipids into fatty acids and hydrophilic groups. The phospholipase acts only on the outer layer of the membrane, while the inner layer remains intact. The phospholipase treatment resulted in 80%...

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Enrichment of Mammalian Tissues and Xenopus Oocytes with Cholesterol
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Published on: March 25, 2020

Plasma membrane cholesterol content affects nitric oxide diffusion dynamics and signaling.

Shane Miersch1, Michael Graham Espey, Ruchi Chaube

  • 1Department of Chemistry and Biochemistry University of Windsor, Windsor Ontario N9B 3P4, Canada.

The Journal of Biological Chemistry
|May 1, 2008
PubMed
Summary

Cholesterol in cell membranes hinders nitric oxide (NO) diffusion, impacting NO signaling pathways. Reducing membrane cholesterol restores NO signaling, highlighting cholesterol

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Membrane Biophysics

Background:

  • Nitric oxide (NO) is a crucial signaling molecule with properties influenced by its hydrophobic nature.
  • NO readily partitions into biological membranes, suggesting membrane composition affects its diffusion and signaling.
  • Cholesterol is a key component of plasma membranes, known to modulate membrane fluidity and structure.

Purpose of the Study:

  • To investigate the hypothesis that plasma membrane cholesterol content influences nitric oxide (NO) diffusion and cellular signaling.
  • To elucidate the relationship between cholesterol-induced membrane ordering and the spatial regulation of NO signaling.

Main Methods:

  • Fluorescence lifetime quenching studies using pyrene-labeled liposomes to measure NO diffusion coefficients.
  • Electrochemical measurements across artificial bilayer membranes with varying cholesterol concentrations.
  • Analysis of NO-induced signaling in Niemann-Pick type C1 (NPC1) fibroblasts (high cholesterol) and normal human fibroblasts (NHF), with manipulation of cholesterol levels.

Main Results:

  • Cholesterol significantly decreased NO diffusion coefficients in liposomes (20-40%) and across artificial membranes.
  • NPC1 fibroblasts with elevated membrane cholesterol showed reduced NO-induced activation of soluble guanylyl cyclase and VASP phosphorylation.
  • Modulating membrane cholesterol in both NPC1 and NHF cells directly altered NO-mediated cGMP production and VASP phosphorylation, and extracellular nitrosation.

Conclusions:

  • Plasma membrane cholesterol content directly impacts the physical diffusion of nitric oxide (NO).
  • Cholesterol-mediated changes in membrane fluidity and microdomain structure contribute to the spatial regulation of NO diffusion and signaling.
  • These findings reveal a critical link between membrane lipid composition and the efficacy of NO-based cellular communication.