Challenge the routine! Cholesterol itself is a signal molecule
January 25, 2017 Source: Bio Valley
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)]; Scientists have long been confused about cholesterol. It is biologically necessary; it is obviously also harmful. No one knows what it does in the cell membranes that are most abundant in the cell.
Now, in a new study, researchers from the University of Illinois at Chicago use a groundbreaking optical imaging technology to accurately reveal the location and movement of cholesterol within the cell membrane. Their surprising discovery is that in addition to many other biological effects of cholesterol, it is also a signal molecule that allows information to be transmitted across the membrane. Related research results were recently published in the journal Nature Chemical Biology , entitled "Orthogonal lipid sensors identify transbilayer asymmetry of plasma membrane cholesterol".
Wonhwa Cho, a essay author and professor of chemistry at the University of Illinois at Chicago, said, "Cholesterol is a lipid molecule that has been negatively reported by the media because of its association with cardiovascular disease. It has been well studied, but people have The cellular function is poorly understood. What is its role? Is it a bad lipid? Of course not -- for example, in the brain, lipids account for about half, and cholesterol is the most abundant in the brain. Lipid." Cholesterol deficiency can cause a variety of diseases, and it is the starting material for more than a dozen or so steroid hormones in the body.
Ear's earlier studies have confirmed that cholesterol interacts with many regulatory molecules, most of which are cellular proteins.
Cho said, “We already know that it can play an important role in cell regulation (such as proliferation or development). We also know that a high-fat diet that raises cholesterol levels is associated with an increased incidence of cancer. How is this achieved? Not fully understood."
He said that one of the biggest problems conceptually is that a lipid that regulates or conducts signal transduction should exist only briefly to transmit information.
He said, "But cholesterol is always there." Cell membranes contain up to 90% of total cellular cholesterol, and cholesterol accounts for about 40% of cell membrane lipids.
Cholesterol keeps the cell membrane (actually a bilayer lipid molecule) stable. Cholesterol is concentrated in the "lipid". Lipids are thought to act as a platform for other signaling molecules to function.
Cho said, "But in this study, we confirmed that a single cholesterol molecule is itself a signal trigger."
Cho said that before this, scientists believe that cholesterol is in the bilayer of the cell membrane, "and may be more likely to be present in the inner layer. However, for the first time in real time, we measured the inner layer of cholesterol in the cell membrane in living cells. The level in the outer layer. We confirmed that cholesterol is mainly present in the outer layer."
They found that cholesterol accounts for about 40% of the outer layer of the cell membrane, about 3% of the inner layer. When responding to a particular cellular stimuli, the amount of cholesterol in the inner layer more than doubled, while the outer cholesterol levels dropped by the same amount.
They also found that although the concentration of cholesterol in the inner layer is low in normal cells, it has a relatively high concentration in cancer cells. Cho said, “We have verified this in many different cell lines.â€
This new study has a positive side to the side effects of statins that reduce cancer risk. Cho and his colleagues found that treating cells with a statin reduced cholesterol levels in the inner layer of the cell membrane, which led to inhibition of cell growth. Cho said this suggests a new way to treat cancer by regulating cell cholesterol levels.
He said, "I think we are only initially understanding the regulation of cholesterol. We have a lot of unpublished data indicating that cholesterol is involved in a series of cellular processes and regulation."
Cho said that lipid molecules such as cholesterol are "hard to study" because they cannot dissolve in water like most biological molecules. This makes it very challenging to develop techniques for quantitatively testing them.
He said, "We have to design a new strategy." Six years ago, he and his colleagues developed an optical imaging technology that allowed direct quantitative detection of lipids in living cells. They use a fluorescent sensor molecule to label a lipid-binding protein that changes color when the protein binds to the lipid. This color change can indicate the proportion of lipid-binding proteins bound to the free lipid molecules, allowing them to determine how many lipids are present at a given location on the cell membrane.
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