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 Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>