Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hormones and drugs that control blood pressure also control malaria infection

19.09.2003


Hormones that regulate cardiovascular function have been discovered to influence malaria infection. As a consequence, beta-blockers, which are safe, inexpensive and commonly prescribed drugs used worldwide to treat high blood pressure, are effective against the deadliest and most drug-resistant strain of malaria parasites.


These findings, by Kasturi Haldar, Jon Lomasney, Travis Harrison and colleagues at the Feinberg School of Medicine at Northwestern University, were reported in an article in the Sept. 19 issue of the journal Science.

Rather than targeting the parasite that causes malaria, an approach that has resulted in mounting resistance to a variety of antimalarial drugs, Haldar and co-researchers focused instead on identifying and blocking the process by which red blood cells allow parasite entry.

Haldar is Charles E. and Emma H. Morrison Professor in Pathology and professor of microbiology-immunology at the Feinberg School.



Malaria is a blood-borne illness transmitted by mosquitoes. Forty percent of the world’s population lives at risk for infection and between 200 and 300 million people are afflicted each year, particularly in underdeveloped and impoverished tropical and sub-Saharan countries.

The most virulent form of the four human malaria parasite species, Plasmodium falciparum, kills over 1 million children each year and is responsible for 25 percent of the infant mortality in Africa, according to latest estimates by the World Health Organization. Recently, however, P. falciparum also has been confirmed as the cause of over 50 cases of malaria among the 625 U.S. troops sent into Liberia. Another strain of malaria, P. vivax, has been confirmed in seven cases in Florida.

World wide there has been a resurgence of malaria in recent years, due mainly to the parasite’s growing resistance to drugs and the mosquito’s acquired resistance to insecticides developed to control the spread of the disease.

Athough malaria infects both liver and blood cells, it is during the “blood stage” of malaria -- when infected red blood cells that are “incubating” thousands of parasites literally explode and release more parasites into the blood stream -- that the symptoms of malaria occur. These symptoms include fever and flu-like symptoms such as chills, headache, muscle aches and fatigue. Immunity is slow to develop, and left untreated, malaria may be fatal, taking its greatest toll in children.

Blocking blood-stage infection by preventing the entry of the P. falciparum parasite into red blood cells provides the most direct way to control infection and quell the symptoms of malaria. But how red blood cells allow the entry of malaria parasites was unknown.

Travis Harrison, who is first author on the article and a research assistant in Haldar’s laboratory, found that G proteins in the red blood cell may be used by the parasite.

G proteins are essentially “go-betweens,” or transducers, that translate signals from hormones, neurotransmitters and other substances and in turn activate such cell processes as gene transcription, motility, secretion and contractility. G proteins have been intensively studied in a wide range of cells, but their functions in oxygen-carrying red blood cells are only beginning to be understood, Haldar said.

Research by Haldar and co-investigators showed that a G protein subunit, called Gs, concentrates around the malaria parasite during infection of the red blood cell.

Using special peptides, compounds similar to proteins, that inhibited the interaction of Gs protein, the researchers were able to show in several laboratory models of malaria that blocking the Gs signal resulted in decreased malaria infection.

Two major Gs-associated receptors, the beta-adrenergic and the adenosine receptors, are known to be present in red blood cells. Stimulating these receptors with a drug called an agonist increased infection of P. falciparum, while beta-blockers, which are antagonists, prevented the P. falciparum parasite from entering red blood cells.

“The use of beta-receptor antagonists, such as those already used to treat high blood pressure, may provide new approaches for treating malaria. Since beta-blockers are directed against a host target, there is low chance of rapid emergence of resistance to these drugs. Moreover, they may be used in combination therapy with existing drugs against parasite targets,” Lomasney and Haldar said.

“This finding offers the opportunity to use well-characterized, inexpensive drugs for a new, much-need application and the impetus for the development of new beta-blockers and other drugs to be tested for effectiveness against malaria,” they said.

Haldar’s co-authors on this study were Travis Harrison, Benjamin U. Samuel, and Thomas Akompong, departments of pathology and of microbiology-immunology, Feinberg School of Medicine; Heidi Hamm, Vanderbilt University, Nashville; Narla Mohandas, New York Blood Center, New York; and Jon W. Lomasney professor of pathology, Feinberg School of Medicine.



Grants from the National Institutes of Health supported this study.

KEYWORDS: malaria, Plasmodium falciparum, G protein, beta-blockers

CONTACT: Elizabeth Crown at (312) 503-8928 or at e-crown@northwestern.edu
Broadcast Media: Tamara Kerrill at (847) 491-4888 or tlk@northwestern.edu

Elizabeth Crown | EurekAlert!
Further information:
http://www.nwu.edu/

More articles from Health and Medicine:

nachricht Sugar entering the brain during septic shock causes memory loss
23.04.2019 | Rensselaer Polytechnic Institute

nachricht Deep stimulation improves cognitive control by augmenting brain rhythms
04.04.2019 | Picower Institute at MIT

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum gas turns supersolid

Researchers led by Francesca Ferlaino from the University of Innsbruck and the Austrian Academy of Sciences report in Physical Review X on the observation of supersolid behavior in dipolar quantum gases of erbium and dysprosium. In the dysprosium gas these properties are unprecedentedly long-lived. This sets the stage for future investigations into the nature of this exotic phase of matter.

Supersolidity is a paradoxical state where the matter is both crystallized and superfluid. Predicted 50 years ago, such a counter-intuitive phase, featuring...

Im Focus: Explosion on Jupiter-sized star 10 times more powerful than ever seen on our sun

A stellar flare 10 times more powerful than anything seen on our sun has burst from an ultracool star almost the same size as Jupiter

  • Coolest and smallest star to produce a superflare found
  • Star is a tenth of the radius of our Sun
  • Researchers led by University of Warwick could only see...

Im Focus: Quantum simulation more stable than expected

A localization phenomenon boosts the accuracy of solving quantum many-body problems with quantum computers which are otherwise challenging for conventional computers. This brings such digital quantum simulation within reach on quantum devices available today.

Quantum computers promise to solve certain computational problems exponentially faster than any classical machine. “A particularly promising application is the...

Im Focus: Largest, fastest array of microscopic 'traffic cops' for optical communications

The technology could revolutionize how information travels through data centers and artificial intelligence networks

Engineers at the University of California, Berkeley have built a new photonic switch that can control the direction of light passing through optical fibers...

Im Focus: A long-distance relationship in femtoseconds

Physicists observe how electron-hole pairs drift apart at ultrafast speed, but still remain strongly bound.

Modern electronics relies on ultrafast charge motion on ever shorter length scales. Physicists from Regensburg and Gothenburg have now succeeded in resolving a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

Fraunhofer FHR at the IEEE Radar Conference 2019 in Boston, USA

09.04.2019 | Event News

 
Latest News

Marine Skin dives deeper for better monitoring

23.04.2019 | Information Technology

Geomagnetic jerks finally reproduced and explained

23.04.2019 | Earth Sciences

Overlooked molecular machine in cell nucleus may hold key to treating aggressive leukemia

23.04.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>