|
RESEARCHERS FIND KEY PATHWAY LINKING OXIDATION CHEMICAL REACTION TO HEART FAILURE
08 March 2005 - Boston University
| Enlargement (or hypertrophy) of the heart muscle is a disease process underlying heart failure. Although reactive oxygen species are known to be involved in this process, relatively little is known about precisely how ROS, highly reactive molecules that arise from incomplete chemical reaction of oxygen, activate the pathways that direct cardiac myocytes to enlarge. |
ROS can cause tissue damage but also are involved in the regulation of cell growth, consequently they are important for the study of biochemical processes in normal and diseased cells. Stimulation of the α-adrenergic receptor causes hypertrophy in adult rat cardiac myocytes in culture, thus providing a useful model to study the cellular mechanisms of cardiac hypertrophy. A small protein, Ras, that contains sulfur molecules (thiols), is known to be activated following α-adrenergic receptor stimulation and to mediate molecular signaling events leading to hypertrophy. Ras was studied to understand the precise mechanisms of ROS interactions with its thiols. According to a study published in this month’s issue of Circulation, researchers at Boston University School of Medicine found that α-adrenergic receptor stimulation produces ROS that modify thiols of Ras. In chemical terms, this is known as an “oxidative modification” of Ras thiols. Furthermore, they found that the chemical reaction of ROS with Ras thiols can be prevented if the endogenous level of thioredoxin-1, a protein capable of protecting protein thiols in the cell, is increased by viral gene transfer. It was further shown that preventing the oxidative modification of Ras thiols also inhibited α-adrenergic receptor-stimulated hypertrophy. “This is the first direct demonstration that an oxidative modification of a small signaling protein, Ras, mediates myocyte hypertrophy,” said lead author Wilson Colucci, MD, chairman of the department of cardiology at BUSM, and chief of cardiology at Boston Medical Center. These observations he said, show how those ubiquitous ROS molecules that we get from incomplete cellular processes can interact with protein thiols in a damaging way, playing an important role in cardiac disease. Furthermore, according to the researchers, these observations raise the possibility that by knowing the way in which the interaction takes place, new treatments may be developed to protect thiols from oxidative modification. This project was funded with Boston University and Federal funds to Dr. Colucci through NIH/NHLBI and as part of the NHLBI Proteomics Initiative from the National Heart, Lung, and Blood Institute, National Institutes of Health, under Contract No. N01-HV-28178.
http://www.bu.edu/
About: Boston University
Boston University has a well-deserved reputation for excellence in research in a wide range of disciplines and a demonstrated commitment to fostering innovative interdisciplinary research. The Office of the Associate Provost for Research and Graduate Education supports the University in facilitating research at the both the student and faculty levels.Our mission is to enhance and encourage research at Boston University and to provide a climate conducive to maintaining the University at the cutting edge of research and scholarly activities. We work with the Boston University community to plan and coordinate interdisciplinary research and represent the University in research matters related to Inter-University consortia. To encourage new, innovative, and cross-disciplinary efforts, this office administers the Special Program for Research Initiation Grants (SPRInG). We showcase graduate research at Science & Technology Day. This annual event features nearly 200 research posters by graduate students from both the Medical and Charles River Campuses working in a wide range of disciplines. Our annual research magazine, Research at Boston University, informs a wide audience about a selection of our significant research findings and ongoing studies at Boston University. We also maintain a strong presence on the web through this site and through the Science Coalition’s website, which brings our research successes to the attention of Congress and other policy makers in the federal government. To assist Boston University researchers, this office oversees the Undergraduate Research Opportunities Program and coordinates with the Office of Sponsored Programs on the Charles River Campus , the research administration on the Medical Campus, the Office of Research Compliance, and the various graduate programs. For the development of commercially viable ideas, we administer the Provost's Innovation Fund and work closely with the Office of Technology Transfer. We also coordinate proposals where there are institutional limits to the number of proposals that may be submitted, cost sharing requirements, significant laboratory renovations, or other special circumstances. This office assists departments and centers to achieve a diverse faculty and graduate student body through our membership and activities with the Northeast Alliance for Graduate Education and the Professoriate and through our affiliation with the Clare Boothe Luce program of the Henry Luce Foundation. |
More News:
• For March 2005
• From Boston University
• For University
|
