Featured Research

from universities, journals, and other organizations

Cell Membrane Plays Crucial Role In Releasing Nitric Oxide From Red Blood Cells

Date:
February 2, 2001
Source:
Duke University Medical Center
Summary:
Duke University Medical Center researchers report that the membranes of red blood cells are actively involved in storing and releasing nitric oxide, a molecule that regulates blood flow and oxygen delivery in humans.

DURHAM, N.C. – Duke University Medical Center researchers report that the membranes of red blood cells are actively involved in storing and releasing nitric oxide, a molecule that regulates blood flow and oxygen delivery in humans.

Related Articles


The findings, published in the Feb. 1 issue of the journal Nature, could help improve understanding and treatment of cardiovascular side effects associated with a number of diseases, including diabetes and sickle cell anemia, and with medical treatments such as blood transfusion or the use of blood substitutes, said Dr. Jonathan Stamler, the study's principal investigator and a professor of medicine.

"It's clear from our work that there exists a crucial relationship between nitric oxide (NO), oxygen, hemoglobin and red blood cells for appropriate dilation of blood vessels and delivery of oxygen to tissues," said Stamler, also a Howard Hughes Medical Institute investigator at Duke University Medical Center. "It's time to look at the role of red blood cells in these diseases. Faulty interaction of nitric oxide, hemoglobin and red blood cells may help explain cardiovascular morbidity."

In particular, Stamler noted that recent studies elsewhere have shown that blood transfusion and administering a drug called erythropoeitin, which increases red blood cell production, are associated with increases in unwanted cardiovascular side effects. There also are documented changes in red blood cell structure and function in sickle cell crisis, high blood pressure and pulmonary vascular disease, he said.

"In all these instances, the red blood cells are probably deficient in NO, and we've shown in this study that we can put NO back," he said.

While the scientists reported in 1996 that hemoglobin binds NO inside red blood cells, the importance of the red blood cell membrane in releasing NO from the cell wasn't recognized until now. The research was funded by the Howard Hughes Medical Institute.

Due in large part to Stamler's work over the past five years, the image of NO has changed from merely being a noxious atmospheric gas to also being one of the most important molecules in the human body, responsible for such vital functions as controlling blood pressure and coordinating the expansion and contraction of blood vessels.

A remaining question had been how NO can move from inside red blood cells, where it is bound to the hemoglobin molecule, to outside the blood cells where it can interact with the smooth muscle cells surrounding the blood vessels to cause dilation of the vessels. While both oxygen and NO can diffuse into red blood cells, only oxygen can diffuse back out.

"We've shown that red blood cell membranes are little pumps for nitric oxide. We've also demonstrated a different view of the inside of red blood cells," Stamler said. "The findings point out that red blood cells are unique and complex, and their normal operation is of vital importance."

To solve the puzzle of NO's mobility in blood, lead author Dr. John Pawloski and co-author and assistant professor of medicine Doug Hess examined whole red blood cells. The laboratory's previous work had been carried out with free hemoglobin – hemoglobin molecules without the red blood cells that normally would contain them.

The researchers first proved that hemoglobin interacts with NO when inside red blood cells the same way it does when "free." Most of the hemoglobin binds NO to one of its four iron atoms – the same places it binds oxygen – which renders the NO non-functional. However, some of the hemoglobin binds the NO to a sulfur atom at another specific site, creating what they called S-nitrosothiol (SNO) when Stamler's group first described it in 1996. SNO is an activated version of NO that maintains its function.

To localize the two hemoglobin-NO complexes in the cell, the scientists dismantled the cells, separating the membrane portion from almost everything else. They reported that the oxygen-hemoglobin-SNO complex was associated predominantly with the membrane of the red blood cells, while most of the NO-iron hemoglobin complex was found in the non-membrane portion.

Additional experiments showed that hemoglobin and the cell membrane interact via the bound SNO. Upon release of the hemoglobin's oxygen, the SNO is transferred to the cell membrane, specifically to a protein called AE1, or anion exchanger 1, which is known to swap negatively charged species (anions).

"Red blood cells were thought to be ‘sacks' of hemoglobin," Stamler said. "Instead, we've shown that there are two compartments of hemoglobin and that the cell membrane actively regulates release of NO from the cell. One compartment is in the middle, the other near the membrane."

Furthermore, the scientists found that the cell membrane acts as a reservoir of NO. In experiments in which red blood cells were exposed to nitric oxide and then added to rings of blood vessel muscle in the laboratory, the researchers found that the red blood cells could store functional NO and release it to relax the muscle.

"The idea had been that NO was consumed immediately by hemoglobin when it went into the red blood cell," Stamler explained. "The finding that NO has a lifespan inside the red blood cell shows that things are not happening at all the way it was thought. Not only are the reactions taking place differently than expected, but the whole process is different."


Story Source:

The above story is based on materials provided by Duke University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Duke University Medical Center. "Cell Membrane Plays Crucial Role In Releasing Nitric Oxide From Red Blood Cells." ScienceDaily. ScienceDaily, 2 February 2001. <www.sciencedaily.com/releases/2001/02/010202074318.htm>.
Duke University Medical Center. (2001, February 2). Cell Membrane Plays Crucial Role In Releasing Nitric Oxide From Red Blood Cells. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2001/02/010202074318.htm
Duke University Medical Center. "Cell Membrane Plays Crucial Role In Releasing Nitric Oxide From Red Blood Cells." ScienceDaily. www.sciencedaily.com/releases/2001/02/010202074318.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins