Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists discover new molecular pathway involved in wound-healing and temperature sensation

29.06.2011
The surprising finding in skin cells could lead to better drugs

Scientists from The Scripps Research Institute have identified a surprising new molecular pathway in skin cells that is involved in wound-healing and sensory communication.

The new study, published in Nature Communications on June 28, 2011, shows that in this process skin cells produce nitric oxide, a versatile signaling molecule involved in temperature-sensing and wound-healing. This alternative, oxygen-independent mode of nitric oxide production previously had been thought to occur only outside cells.

"This alternative nitric oxide production process could prove to be crucial in the clinic," said Ardem Patapoutian, a professor at the Dorris Neuroscience Center at Scripps Research and the senior author of the study. "The usual nitric oxide production process requires oxygen, so drugs that target that process might not work when oxygen availability is low after blood supply disruption."

Studying the Biology of Sensation

Patapoutian's lab focuses on the molecular biology of skin-based sensory pathways—pathways that typically start with stimulus-sensing receptors on nerve ends. Such receptors include the TRPV (transient receptor potential vanilloid) class of receptors, which are sensitive to various temperature- and pain-related stimuli. One of these receptors, TRPV3, is found not only on some nerve cells and nerve ends, but also on outer skin cells known as keratinocytes.

In 2005, Patapoutian's lab reported in the journal Science that TRPV3 seemed to be a heat-sensing receptor; mice bred without it lacked a normal sensitivity to moderately warm stimuli. "That and previous findings made us suspect that TRPV3-expressing keratinocytes are somehow involved in sending thermosensory signals to local nerve ends," said Patapoutian.

In the current study, Patapoutian, his graduate student Takashi Miyamoto, and their colleagues demonstrated that TRPV3 activation leads to the production of nitric oxide in keratinocytes—which suggests that nitric oxide is the carrier of thermosensory signals from skin cells to nearby nerve ends. A simple gas consisting of one atom of nitrogen bound to one atom of oxygen, nitric oxide is one of the more evolutionarily ancient biological signaling molecules, and even plays a role as a neurotransmitter in the brain.

"Nitric oxide was high on our list of possibilities because it is known to be produced in keratinocytes when they are warmed," said Miyamoto, who was first author of the study.

A Surprising Result

Miyamoto applied compounds that are known activators of TRPV3 to cultured mouse keratinocytes, and observed that the cells sharply increased their production of nitric oxide.

"The surprise was that I couldn't find evidence that the nitric oxide was being produced in the normal way, with nitric oxide synthase (NOS) enzymes," he said. The keratinocytes turned out to be producing nitric oxide through a different process, which is known to occur in saliva and other bodily fluids, but hadn't yet been seen in cells.

This alternative nitric oxide production occurs by the stripping of oxygen atoms from compounds called nitrites, which normally come from dietary sources. When Miyamoto deprived the cultured cells of nitrites, their TRPV3-triggered production of nitric oxide dropped to near zero.

To confirm the role of nitrites in this pathway, Miyamoto compared the mice bred without TRPV3—which don't distinguish two different innocuous warm temperatures—to those with no-nitrite diets. "The behavior of the no-nitrite mice was basically the same as that of the TRPV3-knockout mice," he said. Feeding TRPV3-knockout mice with no-nitrite diets had no additive effect, which again suggested that the two work on the same pathway.

Next, the scientists asked, "If nitric oxide is a messenger that delivers temperature-sense signals from skin cells to nearby nerve ends, then to what nerve-end receptor does it bind?" Miyamoto, Patapoutian, and their colleagues suspected TRPV1, a known pain and temperature sensor on nerve ends, which their lab had shown to be activated by nitric oxide, in a study published in 2009. In the present study, they used a chemical to block the activity of TRPV1 receptors in mice, and observed that the lack of TRPV3 or nitrites no longer made a difference in the animal's behavior—a result consistent with the idea that TRPV1 is the main nerve-end receptor on this thermosensory pathway, acting directly or indirectly.

Hints of Things to Come

Nitric oxide's versatility as a signaling molecule also led the researchers to look for other processes in which the TRPV3-mediated pathway might be involved. "We found evidence that the nitric oxide produced by this pathway makes a partial contribution to wound-healing and also specifically to the keratinocyte migration that occurs during wound healing," said Miyamoto.

The team now plans to detail the elements of the TRPV3-activated nitric oxide pathway in temperature sensing, and to look for evidence that the same kind of nitrite-dependent pathway is involved in other nitric oxide-producing cells throughout the body.

"The dogma has been that nitric oxide can be produced in cells only with NOS enzymes, but this study hints that nitrite-based nitric oxide production could potentially be just as important," Miyamoto said.

In addition to Patapoutian and Miyamoto, other co-authors of the study, "TRPV3 regulates nitric oxide synthase-independent nitric oxide synthesis in the skin," were Matt J. Petrus and Adrienne E. Dubin, also of the Patapoutian lab at Scripps Research. For more information, see http://www.nature.com/ncomms/journal/v2/n6/abs/ncomms1371.html

Funding for the study was provided by the National Institutes of Health, Novartis Research Foundation, and the Skaggs Institute for Chemical Biology at Scripps Research.

About The Scripps Research Institute

The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neuroscience, and vaccine development, as well as for its insights into autoimmune, cardiovascular, and infectious disease. Headquartered in La Jolla, California, the institute also includes a campus in Jupiter, Florida, where scientists focus on drug discovery and technology development in addition to basic biomedical science. Scripps Research currently employs about 3,000 scientists, staff, postdoctoral fellows, and graduate students on its two campuses. The institute's graduate program, which awards Ph.D. degrees in biology and chemistry, is ranked among the top ten such programs in the nation. For more information, see www.scripps.edu .

Mika Ono | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Life Sciences:

nachricht Hunting pathogens at full force
22.03.2017 | Helmholtz-Zentrum für Infektionsforschung

nachricht A 155 carat diamond with 92 mm diameter
22.03.2017 | Universität Augsburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Pulverizing electronic waste is green, clean -- and cold

22.03.2017 | Materials Sciences

Astronomers hazard a ride in a 'drifting carousel' to understand pulsating stars

22.03.2017 | Physics and Astronomy

New gel-like coating beefs up the performance of lithium-sulfur batteries

22.03.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>