 |
|
Fox Chase Researchers Give Mutants Another Chance
February 12, 2009Researchers at Fox Chase Cancer Center have demonstrated that it might be possible to treat genetic diseases, including some forms of cancer, by "rescuing" the misshapen, useless proteins produced by some mutant genes.
In the current issue of the Journal of Biological Chemistry, available online now, researchers detail how they were able to restore the function of a mutant human gene in a yeast model of disease by manipulating the available amounts of a so-called chaperone protein, named Hsp70, which helps amino acid chains fold into their proper protein form.
"In some cases, despite a mutation, it is possible to coax a misfolded protein back into a functional conformation," says the paper's lead author Warren Kruger, PhD, senior faculty member at Fox Chase. "In essence, we're using Hsp70 to call a biochemical mulligan, a do-over.
"Hsp70 pulls a misfolded amino acid chain apart like a twisted rubber band and allows it to snap back into place, which we found can restore a significant percentage of proteins to working shape," Kruger says. "If this can be done in humans, it could represent a way of reducing the severity - or perhaps correcting - certain hereditary diseases, even some familial cancers."
Kruger and his colleagues are currently studying how to adapt these findings to human disease. While the study was done in a yeast model for human disease, humans possess at least nine members of the Hsp70 family of chaperones. Evidence suggests that it might be feasible to modify the chaperone environment in order to give Hsp70 better opportunities to rescue broken proteins. "The more chances we give Hsp70 proteins to try to 'fix' the output of mutant genes, the more chances are that they will succeed," Kruger says.
Very often, genetic mutations occur when errors in the DNA code substitute one amino acid for another. It is this sort of mutation that is at the center of a disease called cystathionine β-synthase (CBS) deficiency, an inherited metabolic disorder that the Kruger laboratory uses as a genetic model.
Through experiments performed by Laishram Singh, a post-doctoral fellow in the lab, Kruger learned that exposure to alcohol restored the function of a mutant human CBS protein expressed in genetically engineered yeast cells. This exposure activates heat shock proteins, like Hsp70, which help the cell respond to the shock, or damage, from stress. The sudden excess of Hsp70, in turn, had the side effect of rescuing mutated proteins in addition to those damaged by alcohol.
According to Kruger, Hsp70 works in equilibrium with another heat shock protein, Hsp26, as a sort of biochemical damage control system. While Hsp70 acts like a chaperone to restore the function of such proteins, Hsp26 targets the misfolded proteins to the proteosome, the "garbage disposal" of the cell. The two proteins, it seems, function in opposition, competing to clean up damaged proteins within cells.
The relationship between these two proteins may provide an opportunity for intervention, Kruger reasons. When Kruger and his colleagues removed the gene encoding Hsp26 from yeast, they saw a nine-fold increase in the amount of properly functioning human CBS protein. "If we can target Hsp26 and take it out of circulation, we might be able to give Hsp70 more room to operate," Kruger says.
Funding for this research comes from grants from the National Institutes of Health and the Commonwealth of Pennsylvania.
Fox Chase Cancer Center
"Hsp70 pulls a misfolded amino acid chain apart like a twisted rubber band and allows it to snap back into place, which we found can restore a significant percentage of proteins to working shape," Kruger says. "If this can be done in humans, it could represent a way of reducing the severity - or perhaps correcting - certain hereditary diseases, even some familial cancers."
Kruger and his colleagues are currently studying how to adapt these findings to human disease. While the study was done in a yeast model for human disease, humans possess at least nine members of the Hsp70 family of chaperones. Evidence suggests that it might be feasible to modify the chaperone environment in order to give Hsp70 better opportunities to rescue broken proteins. "The more chances we give Hsp70 proteins to try to 'fix' the output of mutant genes, the more chances are that they will succeed," Kruger says.
Very often, genetic mutations occur when errors in the DNA code substitute one amino acid for another. It is this sort of mutation that is at the center of a disease called cystathionine β-synthase (CBS) deficiency, an inherited metabolic disorder that the Kruger laboratory uses as a genetic model.
Through experiments performed by Laishram Singh, a post-doctoral fellow in the lab, Kruger learned that exposure to alcohol restored the function of a mutant human CBS protein expressed in genetically engineered yeast cells. This exposure activates heat shock proteins, like Hsp70, which help the cell respond to the shock, or damage, from stress. The sudden excess of Hsp70, in turn, had the side effect of rescuing mutated proteins in addition to those damaged by alcohol.
According to Kruger, Hsp70 works in equilibrium with another heat shock protein, Hsp26, as a sort of biochemical damage control system. While Hsp70 acts like a chaperone to restore the function of such proteins, Hsp26 targets the misfolded proteins to the proteosome, the "garbage disposal" of the cell. The two proteins, it seems, function in opposition, competing to clean up damaged proteins within cells.
The relationship between these two proteins may provide an opportunity for intervention, Kruger reasons. When Kruger and his colleagues removed the gene encoding Hsp26 from yeast, they saw a nine-fold increase in the amount of properly functioning human CBS protein. "If we can target Hsp26 and take it out of circulation, we might be able to give Hsp70 more room to operate," Kruger says.
Funding for this research comes from grants from the National Institutes of Health and the Commonwealth of Pennsylvania.
Fox Chase Cancer Center
Amino Acid Current Events and Amino Acid News RSSComputational microscope peers into the working ribosome
Two new studies reveal in unprecedented detail how the ribosome interacts with other molecules to assemble new proteins and guide them toward their destination in biological cells.
Biologists discover bacterial defense mechanism against aggressive oxygen
Bacteria possess an ingenious mechanism for preventing oxygen from harming the building blocks of the cell.
New research into the mechanisms of gene regulation
A team led by Penn State's Ross Hardison, T. Ming Chu Professor of Biochemistry and Molecular Biology, has taken a large step toward unraveling how regulatory proteins control the production of gene products during development and growth.
Penn Study Provides First Clear Idea of How Rare Bone Disease Progresses
An international team of scientists, led by researchers at the University of Pennsylvania School of Medicine, is taking the first step in developing a treatment for a rare genetic disorder called fibrodysplasia ossificans progressiva (FOP), in which the body's skeletal muscles and soft connective tissue turns to bone, immobilizing patients over a lifetime with a second skeleton.
Vibrations key to efficiency of green fluorescent protein
University of California, Berkeley, chemists have discovered the secret to the success of a jellyfish protein whose green glow has made it the darling of biologists and the subject of the 2008 Nobel Prize in Physiology or Medicine.
Blood test identifies women at risk from Alzheimer's
Middle-aged women with high levels of a specific amino acid in their blood are twice as likely to suffer from Alzheimer's many years later, reveals a thesis from the Sahlgrenska Academy at the University of Gothenburg, Sweden.
Caltech researchers show efficacy of gene therapy in mouse models of Huntington's disease
Researchers at the California Institute of Technology (Caltech) have shown that a highly specific intrabody (an antibody fragment that works against a target inside a cell) is capable of stalling the development of Huntington's disease in a variety of mouse models.
NIAID scientists propose new explanation for flu virus antigenic drift
Influenza viruses evade infection-fighting antibodies by constantly changing the shape of their major surface protein.
Fish vision discovery makes waves in natural selection
Emory University researchers have identified the first fish known to have switched from ultraviolet vision to violet vision, or the ability to see blue light. The discovery is also the first example of an animal deleting a molecule to change its visual spectrum.
A balancing act in Parkinson's disease: Phosphorylation of alpha-synuclein
Both genetic and pathologic data indicate a role for the neuronal protein alpha-synuclein in Parkinson disease.
More Amino Acid Current Events and Amino Acid News Articles
 |
TwinLab Amino Fuel 1000 Body Building Amino Acids, Mega Mass, Tablets, 250-Count Bottle by Twinlab This dietary supplement has body building amino acids for more protein and more muscle. New and improved with 25 percent more protein in the same size tablet. Higher potency and faster absorbing branched chain amino acids, peptide bonded and free amino acids that are essential for building muscle. This supplement helps increase protein synthesis, which optimizes muscle growth. Amino acids are the building blocks of protein. Protein availability is an essential element of building muscle when used as part of a low-fat diet and exercise program. Research shows that when taken orally, peptide-bonded amino acids are absorbed faster than other types of proteins. (These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat,... |
 |
Genesis Amino Acid Tablets, 1900 mg, 325-Count Bottles by Genesis Advanced formula. Pharmaceutical grade. Scientifically formulated 100% natural peptide bond sustained release. Stronger formula. Each Tablet Contains: 1900 mgs of Pharmaceutical Grade Lactalbumin (pancreatic digest). Genesis Amino Acid 1900 mg formula is an excellent amino acid source. The profile includes all of the essential, non-essential and Branch Chain amino acids in an easily assimilated protein coated tablet. Amino Acid 1900 mg provides quick and easy building materials for the body without fattening effects. The L-Tryptophane in this product is naturally occurring in Lactalbumin. There is no manufactured Tryptophane in this product. Because Lactalbumin is a 100% natural product the actual amino acid analysis may vary. |
 |
Dymatize Nutrition Super Amino 4800 MG, 300-Count Caplets by Dymatize Dymatize Super Amino 4800 is a high quality, high - efficiency protein source made from the finest proprietary blend of whey protein isolate, Whey Protein Concentrate, and free form Amino Acids. This custom blend is an excellent source of essential and non - essential amino acids including the valuable Branched Chain Amino Acids (BCAA). Amino acids are the building blocks of muscles and are essential to help create and maintain positive nitrogen balance, which is important for new muscle growth. Amino acids also play a key role in preventing catabolic breakdown of muscle proteins, which help to rebuild muscle tissue after intensive exercise. Dymatize Super Amino 4,800 was designed to be one of the strongest amino acid products available on the market providing you with an astounding 4,800... |
 |
Multiple Amino Acids 500 mg 250 Caps by Swanson Premium Brand We have the aminos you need! Whether you're a serious bodybuilder trying to maximize your muscle mass or a nutrition-conscious dieter seeking a quality source of protein, our Multiple Amino Acids supplement has what you're looking for! It features high-grade dairy protein supplying 18 different amino acids, including all of those deemed essential in human nutrition. |
 |
The Healing Nutrients Within (Volume 1 of 2) (EasyRead Large Edition): Facts, Findings, and New Research on Amino Acids by Eric R. Braverman (Author) Your Personal ''MIRACLE DRUGS'' The two dozen amino acids present in the human body are now being shown to be among the most potent healing substances ever discovered. These constituents of protein are necessary to every life process, but research and clinical work in the last two decades have revealed a vast range of therapeutic functions for amino acids, including: arginine's ability to improve sexual dysfunction phenylalanine's pain-relieving powers tyrosine's addiction-fighting potential and energizing action methionine's role in the treatment of Parkinson's disease and as an antidepressant tryptophan's promising use with hyperactivity cysteine's emergence as one of the body's best free-radical destroyers This update and revision of the landmark book on amino acids covers the... |
 |
TwinLab Amino Fuel 2000 Body Building Amino Acids, Mass, Tablets, 150-Count Bottle by Twinlab TwinLab Amino Fuel features bodybuilding amino acids. An amino acid supplement containing a high tech anabolic formula with 2000 milligrams (per tablet) of L-Carnitine, branched chain amino acids and peptide bonded and free amino acids; all of the highest quality from the natural pancreatic digest of whey protein. The result is protein that is easily digested, absorbable, and utilizable to maximize muscle growth and optimize protein synthesis. Research shows that when taken orally, peptide; bonded amino acids increase nitrogen retention, and are superior for achieving optimum muscle growth. (These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.) |
 |
TwinLab Amino Fuel Anabolic Liquid Amino Acids, Mass, 32-Ounce Bottles (Pack of 2) by Twinlab This dietary supplement contains a fast absorbing anabolic liquid amino acid that has, per serving, 15 grams (15,000 mg) of high quality branched chain, peptide-bonded, and free amino acids; stress B-complex vitamins; energizing complex carbohydrates; and |
 |
Optimum Nutrition Superior Amino 2222 Tabs, Tablets, 325-Count Bottle by Optimum Nutrition Superior Amino 2222 Tabs contain 2222 milligrams (2222 grams) per serving of a superior blend of Amino Acids derived from Whey Protein Concentrate, Soy Protein Isolate, Hydrolyzed Whey Peptides, L-Carnitine, and L-Ornithine HCL. A dietary supplement, Optimum Nutrition's Superior Amino 2222 Tabs is produced and packaged in our own state-of-the-art, OTC approved manufacturing facility in accordance with current Good Manufacturing Practices (cGMP's). |
 |
Anabolic Amino 10000- Healthy N' Fit Amino Acid Formula, 360 Tabs by Healthy N Fit Healthy 'N Fit Anabolic Amino 10000. Over 65% higher potency, formulated to increase muscle mass and strength. Pharmaceutical Grade free form and peptide bond amino acids, L-Configuration in correct proportions to promote anabolic activity. Anabolic Amino 10000 is formulated to increase muscle mass and strength in combination with intense training. |
 |
Amino Revolution by Robert Erdmann (Author) |
| © 2009 BrightSurf.com |