Featured Research

from universities, journals, and other organizations

Biochemists Reduce Sickling, Progression of Sickle Cell Disease in Mice

Date:
May 16, 2014
Source:
University of Texas Health Science Center at Houston
Summary:
New preclinical research on the molecular mechanisms responsible for sickle cell disease could aid efforts to develop much needed treatments for this devastating blood disorder that affects millions worldwide. The sickling of red blood cells is the hallmark of this disease. Normally shaped like a donut, the diseased cells instead have a crescent-like appearance. This can lead to anemia, chest pain, lung problems and stroke.

UTHealth scientists working to learn more about the fundamental causes of sickle cell disease are from left to right Anren Song, Ph.D., Kaiqi Sun, Yang Xia, M.D., Ph.D., and Yujin Zhang, Ph.D.
Credit: The University of Texas Health Science Center at Houston (UTHealth)

New preclinical research on the molecular mechanisms responsible for sickle cell disease could aid efforts to develop much needed treatments for this devastating blood disorder that affects millions worldwide.

At the present time, hydroxyurea is the only Food and Drug Administration-approved medication that decreases the number of pain crises and episodes of acute chest syndrome.

An international research team led by biochemists at The University of Texas Health Science Center at Houston (UTHealth) reduced the sickling of red blood cells in a mouse model of the disease. Results of the study appear in The Journal of Clinical Investigation.

The scientists did this by manipulating a small molecule known as sphingosine-1-phosphate (S1P), which they report is found in elevated levels in people with sickle cell disease.

"Our research could lead to therapeutic opportunities," said Yang Xia, M.D., Ph.D., the study's senior author and a professor in the Department of Biochemistry and Molecular Biology at the UTHealth Medical School. "We validated our findings in isolated blood cells from patients with sickle cell disease."

The sickling of red blood cells is the hallmark of this disease. Normally shaped like a donut, the diseased cells instead have a crescent-like appearance. This can lead to anemia, chest pain, lung problems and stroke.

Xia's lab screened approximately 7,000 metabolites for functional differences between sickle cell disease mice and controls. They found that sickle cell disease significantly increases S1P and that S1P is generated by sphingosine kinase 1 (SphK1).

They are directly proportional, meaning the more SphK1, the more S1P, and vice versa, Xia said.

When SphK1 was inhibited in a mouse model of sickle cell disease, red blood cells lived longer and had less sickling. When the scientists treated blood samples taken from sickle cell disease patients with SphK1 inhibitors, the investigators found a significant reduction in the number of sickle cells.

Extending the cells' life span is particularly important because diseased cells only last from 10 to 20 days compared to about 120 days for healthy cells in humans. Reducing the sickling is also significant because sickled cells are more prone to being damaged when passing through narrow capillaries. This can cause anemia and other dangerous complications.

"This work could lead to novel treatments for sickle cell disease," said Harinder Juneja, M.D., study co-author and director of hematology at the UTHealth Medical School and Memorial Hermann-Texas Medical Center.

"The study has identified a lipid bioactive molecule involved in sickling and disease progression. The study provides a better understanding of the pathogenesis of the disease and reveals a new therapeutic target," Juneja said.

Rod Kellems, Ph.D., study co-author and chairman of the Department of Biochemistry and Molecular Biology at the UTHealth Medical School, added, "This research provides insight into how red blood cells work, revealing that SphK1-mediated elevation of S1P contributes to sickling and promotes disease progression and highlights potential therapeutic opportunities for sickle cell disease."


Story Source:

The above story is based on materials provided by University of Texas Health Science Center at Houston. The original article was written by Rob Cahill. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yujin Zhang, Vladimir Berka, Anren Song, Kaiqi Sun, Wei Wang, Weiru Zhang, Chen Ning, Chonghua Li, Qibo Zhang, Mikhail Bogdanov, Danny C. Alexander, Michael V. Milburn, Mostafa H. Ahmed, Han Lin, Modupe Idowu, Jun Zhang, Gregory J. Kato, Osheiza Y. Abdulmalik, Wenzheng Zhang, William Dowhan, Rodney E. Kellems, Pumin Zhang, Jianping Jin, Martin Safo, Ah-Lim Tsai, Harinder S. Juneja, Yang Xia. Elevated sphingosine-1-phosphate promotes sickling and sickle cell disease progression. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI74604

Cite This Page:

University of Texas Health Science Center at Houston. "Biochemists Reduce Sickling, Progression of Sickle Cell Disease in Mice." ScienceDaily. ScienceDaily, 16 May 2014. <www.sciencedaily.com/releases/2014/05/140516202652.htm>.
University of Texas Health Science Center at Houston. (2014, May 16). Biochemists Reduce Sickling, Progression of Sickle Cell Disease in Mice. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2014/05/140516202652.htm
University of Texas Health Science Center at Houston. "Biochemists Reduce Sickling, Progression of Sickle Cell Disease in Mice." ScienceDaily. www.sciencedaily.com/releases/2014/05/140516202652.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
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:
from the past week

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