Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study sheds light on cause of an AIDS treatment side effect

12.09.2002


Highly Active Antiretroviral Therapy, or HAART, is the standard of care for HIV/AIDS patients and has prolonged the lives of countless persons with the disease. HAART has been associated, however, with the emergence of lipodystrophy syndromes. In this month’s issue of the journal Mitochondrion*, researchers from the National Cancer Institute (NCI), the National Institute of Standards and Technology (NIST), and Purdue University, West Lafayette, Ind., report that protease inhibitors, a component of HAART, can lead to mitochondrial toxicity. The effect, seen in this test tube study, of protease inhibitors on mitochondria could help explain the biology behind lipodystrophy and also could point to possible future therapeutic approaches for the syndrome.



Lipodystrophy is a clinical condition characterized by a poor or uneven distribution of fat cells. This distribution causes large amounts of fat to be stored in inappropriate places, which can lead to lower belly obesity and a buffalo-like hump on the upper back. Lipodystrophy side effects also include diabetes and high levels of cholesterol and triglycerides. There is significant scientific debate about the precise mechanisms and metabolic pathways involved in the development of lipodystrophy.

The clinical features of HAART-associated lipodystrophy are similar to those commonly seen in people with mitochondrial dysfunction. The mitochondrion is the powerhouse of the cell, and interference with its normal processing of proteins and energy production can result in distortion or dysfunction of other cellular processes.


HAART is a combination of potent antiretroviral drugs such as protease inhibitors and nucleoside-analogue reverse transcriptase inhibitors (NRTIs). Researchers have known for many years that NRTIs in HAART cocktail regimens can directly cause mitochondrial toxicity by inhibiting a mitochondrial enzyme called DNA polymerase gamma. However, until now it was unknown whether protease inhibitors had a direct effect on mitochondria, as well, or whether they played a role in mitochondrial toxicity.

"In this study, we have demonstrated that protease inhibitors can directly affect an enzyme called mitochondrial processing protease (MPP), which can lead to mitochondrial dysfunction - possibly contributing to the development of syndromes such as lipodystrophy," said Lauren Wood, M.D., of NCI. While protease inhibitors alone do not necessarily cause lipodystrophy, the combination of direct effects on mitochondria by both protease inhibitors and NRTIs may lead to the condition. Moreover, as a class of drugs, protease inhibitors are highly hydrophobic (water insoluble), and hence may be concentrated in fatty tissues and have a greater impact on mitochondria in those tissues with chronic exposure.

"The protease inhibitors were weak inhibitors of the enzymatic processing system," said Henry Weiner, Ph.D., of Purdue University. "If they were stronger inhibitors it would have likely led to more serious complications in patients." It is not unusual to find that a drug acts on a different target than the one it was designed to affect, which is why there are often side effects from drugs. "This finding that protease inhibitors affect MPP could be useful if one wants to develop inhibitors of MPP for other conditions, such as cancer," said Weiner.

The researchers do not know to what degree MPP inhibition correlates with mitochondrial change or disruption, nor if what they found with isolated mitochondria, in this test tube study, actually occurs in patients using the drug. It is known, however, that both NRTIs and protease inhibitors have direct effects on fat cells, and mitochondrial abnormalities in fat tissue have been described in patients with lipodystrophy.

According to Steven J. Zullo, Ph.D., of NIST (formerly of the National Institute of Mental Health), "Many drugs can adversely affect mitochondria. This study highlights the importance of evaluating the potential short- and long-term effects of drugs on mitochondria before they are recommended for widespread use."

Researchers say that future studies should look at the effect of MPPs on the fatty tissue in patients as opposed to the test tube experiments done for this study. They also recommend that when scientists design new HIV/AIDS drugs, they consider the effects that the drugs might have on mitochondria, and attempt to minimize adverse effects.

NCI Press Office | EurekAlert!
Further information:
http://www.cancer.gov

More articles from Health and Medicine:

nachricht Researchers release the brakes on the immune system
18.10.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

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: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>