Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gut protein found to protect against infection and intestinal breakdown

08.02.2006


A protein that binds to bile in the small intestine may hold the key to preventing infection and intestinal breakdown in people with conditions such as obstructive jaundice or irritable bowel syndrome, researchers at UT Southwestern Medical Center have discovered.



"What we’ve identified is one of the mechanisms for how the body keeps the number of bacteria low in the small intestine, and how it prevents them from getting into other organs," said Dr. Steven Kliewer, professor of molecular biology and the study’s senior author. The study is available this week online and in an upcoming issue of the Proceedings of the National Academy of Sciences.

B ile, which is generated by the liver and flows into the small intestine via a duct, contains harsh acids that help the body absorb nutrients, kill certain bacteria and help keep intact the lining of the intestine, a major barrier against the infiltration of infectious microorganisms. That’s no small task; if the innermost lining of the small intestine alone were unfolded, it would be the size of a tennis court.


When there’s no bile in the intestine, as happens in people with obstructive jaundice or in those who rely on feeding tubes for nourishment, the lining breaks down and bacteria pass through it into the body, sometimes causing the massive blood infection known as sepsis. Simply giving bile acids orally as a substitute isn’t a good solution because they can cause liver damage, Dr. Kliewer said.

The researchers focused on a molecule — FXR — in the wall of the lining, which binds to bile acids. When FXR was activated by a synthetic binding chemical called GW4064, it was found to activate several genes that are known to protect the intestinal lining or attack bacteria.

The research team also found that FXR molecules heavily lined the inside folds of the intestine in adult mice.
"It’s perfectly positioned," Dr. Kliewer said. "It’s expressed in just the right place to protect us from the environment."

When the bile ducts of mice were tied off, preventing bile from reaching the intestine, adding GW4064 prevented damage to the intestines, showing that it can replace bile in protecting the small intestine.

Genetically engineered mice that lacked FXR showed overall damage to the intestines, "strong evidence that this protein is crucial," Dr. Kliewer said. Drugs that bind to FXR, he said, could eventually become useful in treating various conditions of the small intestine.

Other UT Southwestern researchers involved in the study were Drs. Takeshi Inagaki and Guixiang Zhao, postdoctoral research fellows in molecular biology; Dr. Antonio Moschetta, postdoctoral research fellow in pharmacology and a research associate in the Howard Hughes Medical Institute; Youn-Kyoung Lee, student research assistant in molecular biology; Li Peng, senior research associate in molecular biology; John Shelton, senior research scientist in internal medicine; Dr. James Richardson, professor of pathology; Dr. Joyce Repa, assistant professor of physiology; and Dr. David Mangelsdorf, professor of pharmacology and biochemistry and an HHMI investigator. Drs. Ruth Yu and Michael Downes of the Salk Institute for Biological Studies in La Jolla, Calif., also participated in the study.

The work was supported by the National Institutes of Health, the HHMI and The Welch Foundation.

Aline McKenzie | EurekAlert!
Further information:
http://www.utsouthwestern.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 >>>