Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UCSD Medical Researchers Discover Molecular Pathway That Turns a Juvenile Heart into an Adult Heart

14.01.2005


Researchers at the University of California, San Diego (UCSD) School of Medicine have discovered the molecular sequence of events in mice that turn a juvenile heart into an adult heart capable of responding to increased workloads.


Xu et al./Cell



Published as the cover story in the January 14, 2005 issue of the journal Cell, the study identifies a protein called ASF/SF2 as a regulator of a calcium enzyme responsible for heart contraction and tissue growth. Mice born with mutated or absent ASF/SF2 had shortened contractive fiber that appeared locked in a contracted state, leading to sudden death. When ASF/SF2 was normal, heart development progressed normally.

“The cascade of molecular events that we have uncovered are directly relevant to understanding heart physiology during development, and may provide insights into mechanisms that directly contribute to heart attacks in humans,” said the study’s senior author, Xiang-Dong Fu, Ph.D., a UCSD professor of Cellular and Molecular Medicine.


ASF/SF2 are part of a family of proteins that function in a vital cellular process called alternative splicing – the mechanism through which a single gene can generate several kinds of proteins by selecting different combinations of the same set of amino acid building blocks. Alternative splicing occurs at all stages of development, including the period of transition from juvenile to adult life, when many tissues and organs, such as the heart, become mature. Although alternative splicing is widely known, little is understood about how this process occurs in mammals. In a “Preview” appearing in the January 14, 2005 issue of Cell, Thomas A. Cooper of the Departments of Pathology and Molecular and Cellular Biology at Baylor College of Medicine in Houston, noted that the results by Fu’s team “highlight the huge potential and largely unexplored role for alternative splicing during vertebrate development.”

The UCSD researchers used mouse models and sophisticated laboratory procedures in their studies. Mice developed without ASF/SF2 appeared normal at birth, but developed a notable decrease in heart contraction as they neared adulthood. Examining the contractile apparatus in the mutant heart, the investigators found striking structural defects, including shortened contractile tissue called sarcomeres and altered ridges in heart tissue. Follow-up functional studies at the single cell level uncovered a marked alteration in calcium handling, which is a major regulatory function for muscle contraction. Additional findings pointed to an increase in the expression of genes related to excessive cardiac tissue growth (hypertrophy) and fiber growth (fibrosis), which are indicators of a heart condition called dilated cardiomyopathy.

Interestingly, the researchers also found differences in male versus female mice. The male animals experienced greater disease and died earlier than the females with mutated ASF/SF2.

The UCSD study was funded by the National Institutes of Health (NIH). Additional authors were Xiangdong Xu, B.S., UCSD Department of Cellular and Molecular Medicine, and Dongmei Yang, Ph.D., National Institute on Aging, NIH, co-first authors; and Jian-Hua Ding, Ph.D., Huan-You Wang, Ph.D., Zhen Ye, B.S., UCSD Department of Cellular and Molecular Medicine; Wang Wang, Ph.D., Rui-Ping Xiao, Ph.D., and Heping Cheng, Ph.D., National Institute on Aging, NIH; Pao-Hsien Chu, Ph.D., Nancy D. Dalton, B.S. and Ju Chen, Ph.D., UCSD Department of Medicine and Institute of Molecular Medicine; John R. Bermingham, Jr. Ph.D., Forrest Liu, B.S. and Michael G. Rosenfeld, M.D., UCSD Department of Medicine and Howard Hughes Medical Institute; and James L. Manley, Ph.D., Department of Biological Sciences, Columbia University, New York.

Sue Pondrom | EurekAlert!
Further information:
http://health.ucsd.edu/news/
http://www.ucsd.edu

More articles from Life Sciences:

nachricht Enduring cold temperatures alters fat cell epigenetics
19.04.2018 | University of Tokyo

nachricht Full of hot air and proud of it
18.04.2018 | University of Pittsburgh

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

Im Focus: The Future of Ultrafast Solid-State Physics

In an article that appears in the journal “Review of Modern Physics”, researchers at the Laboratory for Attosecond Physics (LAP) assess the current state of the field of ultrafast physics and consider its implications for future technologies.

Physicists can now control light in both time and space with hitherto unimagined precision. This is particularly true for the ability to generate ultrashort...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Diamond-like carbon is formed differently to what was believed -- machine learning enables development of new model

19.04.2018 | Materials Sciences

Electromagnetic wizardry: Wireless power transfer enhanced by backward signal

19.04.2018 | Physics and Astronomy

Ultrafast electron oscillation and dephasing monitored by attosecond light source

19.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>