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 Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex

nachricht New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>