Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

U-M researchers solve a molecular mystery in muscle

16.03.2010
The muscle-building abilities of hormones known as insulin-like growth factors (IGFs) are legendary. Just do an online search and you'll find not only scientific papers discussing the effects of IGFs on the cells that give rise to muscle tissue, but also scores of ads touting the purported benefits of IGF supplements for bodybuilding.

But in spite of widespread interest in these potent molecules, key details about how IGFs work on muscle cells have been lacking.

A research by a team led by University of Michigan molecular biologist Cunming Duan has cleared up a longstanding mystery about the workings of IGFs. The team's findings, scheduled to be published online this week in the Proceedings of the National Academy of Sciences, could lead to new treatments for muscle-wasting diseases and new ways of preventing the muscle loss that accompanies aging.

And because IGFs also are implicated in the growth and spread of malignant tumors, the new insights may have implications in cancer biology.

Like other peptide and protein hormones, IGFs work by binding to receptors on the cells they target. The binding then sets off a cascade of reactions that ultimately direct the cell to do something. You might think that a given hormone, binding to a particular receptor, would always elicit the same response from the cell, but that's not what happens in the case of IGF and myoblasts (immature cells that develop into muscle tissue).

During muscle formation, the binding of IGF to its receptor can prompt either of two very different responses in myoblasts, said Duan, a professor in the Department of Molecular, Cellular and Developmental Biology. Some of the cells are stimulated to divide, while others interpret the very same signal as an order to differentiate (become specialized).

"These are opposite and mutually exclusive cellular events—once a muscle cell divides, it can't differentiate, and once it differentiates, it can never divide again," Duan said. How activation of the same receptor by the same hormone can elicit two such distinctly different responses has been one of the most puzzling questions about IGF, but Duan and colleagues have found the answer.

"The myoblasts' response is controlled by oxygen availability," said Duan. When oxygen levels are normal, IGF promotes muscle cell differentiation; when oxygen levels are below normal, IGF promotes muscle cell division. Teasing out the molecular details, the researchers discovered that low oxygen activates an intermediary called the HIF-1 complex, which reprograms the cascade of steps that ultimately controls the cell's response.

The findings not only reveal how muscle cells respond to varying oxygen levels during normal development, but also have implications for human disease, Duan said. "For example, a major reason that muscle atrophy occurs as people get older is that the IGF signal gets weaker. If we can find a way to affect IGF signaling, we may be able to stop or reverse the loss." Although manipulating the oxygen levels in living cells could be difficult, it may be possible to manipulate HIF-1 in ways that would mimic changing oxygen levels.

The work also could help scientists better understand the processes involved in cancer progression and spread. It's known that IGF can promote tumor cell division and survival and also that oxygen levels are often lower in tumor tissue than in normal tissue. Finding the link between IGF activity and oxygen levels may lead to new strategies for cancer treatment.

Duan's coauthors on the paper are former graduate student Hongxia Ren, now a postdoctoral fellow at Columbia University, and Domenico Accili, professor of medicine at Columbia .

The research was funded by the National Institutes of Health, the National Science Foundation and the University of Michigan.

Contact: Nancy Ross-Flanigan
Phone: (734) 647-1853

Nancy Ross-Flanigan | EurekAlert!
Further information:
http://www.umich.edu

Further reports about: HIF-1 IGF Science TV cell division living cell muscle cells oxygen levels

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>