DATA SYNTHESIS: Lopinavir/ritonavir is a fixed-dose protease ..
10/12/2016 · Kaletra (lopinavir/ritonavir)
The mechanisms by which lopinavir alters muscle protein synthesis have not been investigated previously. In general, regulation of protein synthesis involves changes in the phosphorylation state of several key components of the translation machinery including the phosphorylation of the elongation factor eEF2. Although we did not directly determine rates of elongation in the current study, these results are consistent with the observed reduction in protein synthesis in response to lopinavir. The effect of lopinavir on eEF2 is in agreement with previous studies examining various stressors. For example, treatment with the protease inhibitor indinavir decreased the activity of eEF2 in myocytes . Likewise, alcohol or ATP depletion had a similar effect on the phosphorylation state of this elongation factor [; ].
DATA SOURCES: English-language MEDLINE and AIDSline searches ..
The elongation process consumes a considerable amount of cellular energy, thereby linking protein synthesis and signaling pathways that respond to changes in energy levels. For example, the AMPK pathway is activated in response to various stimuli that affect cellular energy levels. Furthermore, AMPK is known to regulate the activity of eEF2K [; ; ; ]. Thus, AMPK may be an important modulator of the effects of lopinavir on eEF2 phosphorylation. illustrates that lopinavir increased the phosphorylation of AMPK by 2-fold, when compared with control untreated cells. Lopinavir similarly increased the phosphorylation of ACC (), a known downstream substrate of AMPK. Both of these changes were independent of a change in total AMPK or ACC protein. Thus, these data are indicative of an overall increase in the activity of AMPK in myocytes after exposure to lopinavir.