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Researchers report online June 7 in the journal Cell that a type of protein called thrombospondin activates aprotective pathway that prevents heart cell damage in miceundergoing simulated extreme hypertension, cardiac pressureoverload and heart attack. "Our results suggest that medically this protein could betargeted as a way to help people with many different disease stateswhere various organs are under stress,' said Jeffery Molkentin,PhD, lead investigator and a researcher at Cincinnati Children'sHospital Medical Center and the Howard Hughes Medical Institute."Although more study is needed to determine how our findingsmight be applied clinically, a possible therapeutic strategy couldinclude a drug or gene therapy that induces overexpression of theprotein in tissues or organs undergoing injury." Thrombospondin (Thbs) proteins are produced by the body in cellswhere tissues are being injured, reconfigured or remodeled, such asin chronic cardiac disease. They appear in part of the cell'sinternal machinery called the endoplasmic reticulum. There, Thbstriggers a stress response process to regulate production of otherproteins and help correct or rid cells of proteins that misfold andlose their form and intended function. Misfolded proteins helpdrive tissue damage and organ dysfunction. The researchers zeroed in on how one thrombospondin protein (Thbs4)activates cellular stress responses in mice bred to overexpress theprotein in heart cells. They compared how the hearts of theThbs4-positive mice responded to simulated stress and injury tomice not bred to overexpress cardiac-specific Thbs4. Overexpression of Thbs4 had no effect on the animals prior tocardiac stress -- although during simulated hypertension andcardiac infarction the protein reduced injury and protected themfrom death. Mice not bred for Thbs4 overexpression were extremelysensitive to cardiac injury, according to Molkentin, a member ofthe Division of Molecular Cardiovascular Biology and CincinnatiChildren's Heart Institute. The researchers reported that overexpressed Thbs4 enhanced theability of heart cells to secrete helpful proteins, resolvemisfolded proteins and properly reconstruct extracellular matrix --connective tissues that help give the heart functional form andstructural integrity. Critical to the stress response process was Thbs4 activating andregulating a transcription factor called Aft6alpha. Transcriptionfactors help decode genetic instructions of other genes to controltheir expression. In the case of Aft6alpha in the heart, it helpsmediate repair processes. When Aft6alpha is activated by Thbs4, theendoplasmic reticulum in cells expands and the production ofchaperone molecules and other repair proteins is enhanced. Mice bred not to overexpress cardiac Thbs4 did not exhibitactivated Aft6alpha or robust repair processes following cardiacinjury, leading to their poor outcomes. Molkentin said the research team continues to examine theThbs-dependent stress response pathway to better understand theinvolved processes. This includes seeing how the pathway affectslaboratory models of neurodegenerative diseases like Parkinson's,Alzheimer's and amyotrophic lateral sclerosis Funding support for the study came from the National Institutes ofHealth and Howard Hughes Medical Institute. Collaborating on the study -- along with first author Jeffrey M.Lynch, a member of the Molkentin lab -- were researchers from theDepartment of Pediatrics, Cincinnati Children's and the Universityof Cincinnati (UC), the Department of Surgery at UC and researchersfrom Kyoto University in Japan, Columbia University in New York andBeth Israel Deaconess Hospital and Harvard Medical School, Boston. The e-commerce company in China offers quality products such as Electronic Dry Cabinet , Flammable Storage Cabinet, and more. For more , please visit Flammable Storage Cabinet today!
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