Kenny De Meirleir

Ribonuclease L proteolysis in peripheral blood mononuclear cells of chronic fatigue syndrome patients

A 37-kDa binding polypeptide accumulates in peripheral blood mononuclear cell (PBMC) extracts from chronic fatigue syndrome (CFS) patients and is being considered as a potential diagnostic marker (De Meirleir, K., Bisbal, C., Campine, I., De Becker, P., Salehzada, T., Demettre, E., and Lebleu, B. (2000) Am. J. Med. 108, 99–105). We establish here that this low molecular weight 2-5A-binding polypeptide is a truncated form of the native 2-5A-dependent ribonuclease L (RNase L), generated by an increased proteolytic activity in CFS PBMC extracts. RNase L proteolysis in CFS PBMC extracts can be mimicked in a model system in which recombinant RNase L is treated with human leukocyte elastase. RNase L proteolysis leads to the accumulation of two major fragments with molecular masses of 37 and 30 kDa. The 37-kDa fragment includes the 2-5A binding site and the N-terminal end of native RNase L. The 30-kDa fragment includes the catalytic site in the C-terminal part of RNase L. Interestingly, RNase L remains active and 2-5A-dependent when degraded into its 30- and 37-kDa fragments by proteases of CFS PBMC extract or by purified human leukocyte elastase. The 2-5A-dependent nuclease activity of the truncated RNase L could result from the association of these digestion products, as suggested in pull down experiments.

Pergolide mesylate inhibits exercise-induced prolactin release in man

The effects of Pergolide, a potent dopamine agonist, on exercise-induced plasma prolactin (PRL) changes were studied in normal men. Exercises consisted of a graded bicycle ergometer test and of a 20-km endurance run. In both circumstances, treatment with Pergolide, when compared with placebo or control values, resulted in a significant suppression of basal PRL (P less than 0.001) as well as of exercise-induced PRL increase (P less than 0.01). From these experiments it was concluded that augmented levels of PRL in plasma, as seen during or after muscular exercise, are caused by increased pituitary secretion, rather than decreased elimination.