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 Custom-tailored strategy against glioblastomas
26.09.2016 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

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: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

Using mathematical models to understand our brain

16.09.2016 | Event News

 
Latest News

The Flexible Grid Involves its Users

27.09.2016 | Information Technology

Process-Integrated Inspection for Ultrasound-Supported Friction Stir Welding of Metal Hybrid-Joints

27.09.2016 | Machine Engineering

First quantum photonic circuit with electrically driven light source

27.09.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>