Researchers had reported some of the key molecular events in the immune system in mice, which contribute to inflammation-related diseases, including participation in a particular molecule on the surface of the body's immune cells to fight infection. Now they have stepped forward and revealed the mechanism by which natural medicines interact with abscisic acid in this protein, called peroxisome proliferator-activated receptor gamma, inhibits inflammation and subsequent disease.
"In previous work, our research group has shown that abscisic acid has beneficial effects on various conditions and diseases, including inflammation associated with obesity, diabetes, atherosclerosis and inflammatory bowel disease," said Josep Bassaganya-Riera, Associate Professor of Immunology at the Virginia Bioinformatics Institute, chief of the Nutritional Immunology Group and the Division of Molecular Medicine Institute of the cyberinfrastructure, and principal investigator of the study. "An idea on how to abscisic acid reduces inflammation in these cases is that binds to a specific region of peroxisome proliferator-activated receptor gamma, a binding site is known as the ligand binding domain, which is expected to and exercise medicine to take effect. Our results show that this is not the case and for the first time, we have shown that abscisic acid operates independently of the ligand binding domain of the receptor. "
"This is important because it suggests the existence of new therapeutic targets or other modes of action to address the effects of abscisic acid in the immune system," said Riera-Bassaganya. "Drugs that bind to the ligand binding domain receptor gamma peroxisome proliferator-activated Avandia is associated with serious cardiovascular side effects. However, the mechanism of peroxisome proliferator newfound alternative-activated receptor gamma activation abscisic acid does not appear to be associated with adverse side effects, which represents a promising new therapeutic avenue. "
"The results of this research illustrates the synergy that can result from a combination of experimental and computational methods to characterize therapeutic targets," said David Bevan, assistant professor of biochemistry at Virginia Tech. "Using molecular modeling, we identified a potential site for binding abscisic acid lanthionine synthetase C-2, as the protein, a protein necessary for the beneficial effects on the health of abscisic acid. We also have, again by using docking studies to reveal the reasons for the lack of direct involvement of abscisic acid in activated receptor gamma peroxisome proliferator, which was experimentally validated assays ligand binding. "
"Lanthionine synthase C-2, as the first step in a path that leads to the activation of peroxisome proliferator-activated receptor gamma in immune cells by abscisic acid," said Raquel Hontecillas, assistant professor of immunology at ' Virginia Bioinformatics Institute and one of the principal investigators of the study. "We have also shown that abscisic acid affects the expression of several genes involved in signaling inflammation, and cell metabolism, providing further evidence of possible points of intervention in the treatment of inflammation and autoimmune diseases."
Researchers are still hoping to locate some of the new drug candidates in the molecular network of the immune response, as they continue to dissect how the natural substance abscisic acid reduces damage from inflammation. In addition, new knowledge about how plants abscisic acid will be used to develop new classes of drugs that target the same alternative channel of peroxisome proliferator-activated receptor gamma activation, a potentially safer than the use of Drugs targeted direct connection to the receiver.
The study was funded by the approval number 5R01AT004308 the National Center for Complementary and Alternative Medicine, National Institutes of Health, the European Commission has published the number 224 836, Ramon y Cajal Program, the National Institute of Allergy and Infectious Diseases Contract No. HHSN272200900040C, National Institute of Allergy and Infectious Diseases Contract No. HHSN272201000056C, and funds for Nutritional Immunology and Laboratory of Molecular Medicine.
"In previous work, our research group has shown that abscisic acid has beneficial effects on various conditions and diseases, including inflammation associated with obesity, diabetes, atherosclerosis and inflammatory bowel disease," said Josep Bassaganya-Riera, Associate Professor of Immunology at the Virginia Bioinformatics Institute, chief of the Nutritional Immunology Group and the Division of Molecular Medicine Institute of the cyberinfrastructure, and principal investigator of the study. "An idea on how to abscisic acid reduces inflammation in these cases is that binds to a specific region of peroxisome proliferator-activated receptor gamma, a binding site is known as the ligand binding domain, which is expected to and exercise medicine to take effect. Our results show that this is not the case and for the first time, we have shown that abscisic acid operates independently of the ligand binding domain of the receptor. "
"This is important because it suggests the existence of new therapeutic targets or other modes of action to address the effects of abscisic acid in the immune system," said Riera-Bassaganya. "Drugs that bind to the ligand binding domain receptor gamma peroxisome proliferator-activated Avandia is associated with serious cardiovascular side effects. However, the mechanism of peroxisome proliferator newfound alternative-activated receptor gamma activation abscisic acid does not appear to be associated with adverse side effects, which represents a promising new therapeutic avenue. "
"The results of this research illustrates the synergy that can result from a combination of experimental and computational methods to characterize therapeutic targets," said David Bevan, assistant professor of biochemistry at Virginia Tech. "Using molecular modeling, we identified a potential site for binding abscisic acid lanthionine synthetase C-2, as the protein, a protein necessary for the beneficial effects on the health of abscisic acid. We also have, again by using docking studies to reveal the reasons for the lack of direct involvement of abscisic acid in activated receptor gamma peroxisome proliferator, which was experimentally validated assays ligand binding. "
"Lanthionine synthase C-2, as the first step in a path that leads to the activation of peroxisome proliferator-activated receptor gamma in immune cells by abscisic acid," said Raquel Hontecillas, assistant professor of immunology at ' Virginia Bioinformatics Institute and one of the principal investigators of the study. "We have also shown that abscisic acid affects the expression of several genes involved in signaling inflammation, and cell metabolism, providing further evidence of possible points of intervention in the treatment of inflammation and autoimmune diseases."
Researchers are still hoping to locate some of the new drug candidates in the molecular network of the immune response, as they continue to dissect how the natural substance abscisic acid reduces damage from inflammation. In addition, new knowledge about how plants abscisic acid will be used to develop new classes of drugs that target the same alternative channel of peroxisome proliferator-activated receptor gamma activation, a potentially safer than the use of Drugs targeted direct connection to the receiver.
The study was funded by the approval number 5R01AT004308 the National Center for Complementary and Alternative Medicine, National Institutes of Health, the European Commission has published the number 224 836, Ramon y Cajal Program, the National Institute of Allergy and Infectious Diseases Contract No. HHSN272200900040C, National Institute of Allergy and Infectious Diseases Contract No. HHSN272201000056C, and funds for Nutritional Immunology and Laboratory of Molecular Medicine.
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