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 Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

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: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>