The Body Covers: The 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention
Upregulation of the Mitochondrial PRSS15/LON During Lipodistrophy: An Interview With Marcello Pinti, Ph.D.
July 24, 2007
We then focused our attention on the role of certain genes whose proteins are expressed in mitochondria. It is well known that mitochondria are relevant for the onset of lipodystrophy. In particular, we have shown that one of these genes -- it's called LON or PRSS15 -- is probably important in the onset of this disease, because it has many different roles in mitochondria, one being the ability to bind to mitochondrial DNA.
We have also demonstrated that -- when you treat cells, you use a cell model in vitro -- when you treat cells with drugs used for HAART, you have change in expressions in these genes. [The changes] are due not to the simple depletion of mitochondrial DNA (as shown in many other papers during recent years), but due mainly to the production of reactive oxygen species (ROS) that are caused by, for example, stavudine (d4T, Zerit).
Are they also caused by the newer medications? Stavudine's not used that much anymore.
We have used stavudine as a model because it is known to be one of the drugs that has a higher impact on mitochondria. That's why we used this drug. Now we plan to do some experiments with other NRTIs [nucleoside reverse transcriptase inhibitors].
So what's the next step?
We want to try to see if the depletion -- the activity in vitro of this protein -- can cause in the cells the same effect that we find when we have chronic treatment of patients with d4T. We use an in vitro model of cells that are liposarcoma cell-lines, so cells that are similar to adipose tissue.
What are the limitations of the study?
Until now, the data that we obtained regarding the ROS, the reactive oxygen species, are mainly cellular model. We have to try to confirm some of these aspects.
Has this ever been done before?
Click here to view the study abstract from Dr. Pinti's presentation.
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