Navigation Links
Why a hereditary anemia is caused by genetic mutation in mechanically sensitive ion channel
Date:3/8/2013

BUFFALO, N.Y. A genetic mutation that alters the kinetics of an ion channel in red blood cells has been identified as the cause behind a hereditary anemia, according to a paper (http://bit.ly/13LgCzc) published this month in the Proceedings of the National Academy of Sciences by University at Buffalo scientists and colleagues.

The research team was led by Frederick Sachs, PhD, SUNY Distinguished Professor in the UB Department of Physiology and Biophysics, who discovered in the 1980s that some ion channels are mechanosensitive, that is, they convert mechanical stress into electrical or biochemical signals.

The findings of the new study are significant, Sachs says, because it is the first time defects in a mechanosensitive ion channel have been implicated as the cause of a disease.

"We found that the mutations in the gene that codes for the ion channel called PIEZO1 causes the channel to stay open too long, causing an ion leak in red cells," explains Sachs. "Calcium and sodium enter, and potassium leaves, and that affects the ability of the red cell to regulate its volume. The cells become dehydrated and can break open, releasing their hemoglobin into the blood, and causing symptoms, such as the shortness of breath seen in anemic patients."

The anemia that results from the mutations in PIEZO1 is called familial xerocytosis, a mild to moderate form of anemia. The ion channel, PIEZO1, is about 10 nanometers across, and it increases its dimensions significantly upon opening; that change in dimensions is what is responsible for its mechanical sensitivity.

Mechanosensitive ion channels are likely to play a role in many diseases, since all cells are mechanically sensitive. Sachs and his colleagues have worked on activation of these channels in Duchenne muscular dystrophy, which is caused by errors in a gene coding for a fibrous protein that reinforces the cell membrane. The increased stress caused by this loss of reinforcement causes the channels to open and the leak of calcium is likely what causes the muscles to atrophy, Sachs explains.

Sachs and colleagues at UB founded a biotech company in Buffalo, Tonus Therapeutics to create a therapy for muscular dystrophy based on a peptide they discovered that inhibits the channels involved in that disease. They originally discovered the peptide in a tarantula venom but now it is synthesized chemically. The peptide has received orphan drug designation from the FDA.

"We were pleased to find that our spider venom peptide also inhibits the PIEZO1 channel," says Sachs.

"This means our peptide could be a potential therapy in blood diseases, where there are defects in the ways that red blood cells regulate cell volume," he says.

In normal cells, he says, the mechanosensitive ion channels usually remain closed.

"I think the cells use them as emergency valves so the only time they open is when cells are under extreme stress," he explains. "Consequently, our peptide doesn't bother healthy cells, so it's nontoxic. It only affects unhealthy cells, cells which are mechanically stressed."


'/>"/>

Contact: Ellen Goldbaum
goldbaum@buffalo.edu
716-645-4605
University at Buffalo
Source:Eurekalert

Related biology news :

1. Nature study reveals loss of essential blood cell gene leads to anemia
2. Dinosaur bends caused by prolonged diving
3. Insecticide resistance caused by recombination of 2 genes
4. Einstein researcher receives $10.8 million grant to study toxic blood reactions caused by hemoglobin
5. Tsunami caused long-term ecosystem change in the Caribbean
6. Evidence contradicts idea that starvation caused saber-tooth cat extinction
7. A neurosteroid found to prevent brain injury caused by HIV/AIDS
8. Nearby chimpanzee populations show much greater genetic diversity than distant human populations
9. Will a genetic mutation cause trouble? Ask Spliceman
10. UC Santa Barbara researchers discover genetic link between visual pathways of hydras and humans
11. Perception and preference may have genetic link to obesity
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/26/2016)... LONDON , April 26, 2016 /PRNewswire/ ... Systems, a product subsidiary of Infosys (NYSE: ... partnership to integrate the Onegini mobile security platform ... http://photos.prnewswire.com/prnh/20151104/283829LOGO ) The integration ... security to access and transact across channels. Using ...
(Date:4/15/2016)... Research and Markets has announced ... 2016-2020,"  report to their offering.  , ... global gait biometrics market is expected to grow ... 2016-2020. Gait analysis generates multiple variables ... to compute factors that are not or cannot ...
(Date:3/31/2016)... , March 31, 2016  Genomics firm Nabsys has ... CEO, Barrett Bready , M.D., who returned to ... the original technical leadership team, including Chief Technology Officer, ... Product Development, Steve Nurnberg and Vice President of Software ... the company. Dr. Bready served as CEO ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... MONICA, Calif. , June 23, 2016  The Prostate Cancer Foundation ... pioneer increasingly precise treatments and faster cures for prostate cancer. Members of the ... institutions across 15 countries. Read More About the Class ... ... ...
(Date:6/23/2016)... , ... June 23, 2016 , ... ... announced the launch of the Supplyframe Design Lab . Located in Pasadena, ... explore the future of how hardware projects are designed, built and brought to ...
(Date:6/23/2016)... LOUISVILLE, Ky. , June 23, 2016 /PRNewswire/ ... from two Phase 1 clinical trials of its ... double-blind, placebo-controlled, single and multiple ascending dose studies ... and pharmacodynamics (PD) of subcutaneous injection in healthy ... APL-2 subcutaneously (SC) either as a single dose ...
(Date:6/23/2016)... YORK , June 23, 2016 ... trading session at 4,833.32, down 0.22%; the Dow Jones Industrial ... S&P 500 closed at 2,085.45, down 0.17%. Stock-Callers.com has initiated ... INFI ), Nektar Therapeutics (NASDAQ: NKTR ), ... Therapeutics Inc. (NASDAQ: BIND ). Learn more about ...
Breaking Biology Technology: