Enhancement of the citrulline-nitric oxide cycle in astroglioma cells by the proline-rich peptide-10c from Bothrops jararaca venom.

The biological activity of the proline-rich decapeptide Bj-PRO-10c, a processing product of the C-type natriuretic peptide precursor protein, expressed in the brain and the venom gland of the pit viper Bothrops jararaca, was originally attributed to the inhibition of the somatic angiotensin-converting enzyme activity with subsequent anti-hypertensive effect. However, recent results suggest broader biological activity may also be involved in the cardiovascular effects of this peptide. Here we show that Bj-PRO-10c enhances and sustains the generation of nitric oxide (NO) by regulating argininosuccinate synthase activity and thereby velocity of the citrulline-NO cycle. Bj-PRO-10c-mediated effects not restricted to the cardiovascular system, since NO production was also induced in cells of astroglial origin. Bj-PRO-10c was internalized by C6 astroglioma cells where it induces NO production and upregulation of the citrulline-NO cycle cells in a dose-dependent fashion. In view of that, astroglial cells function as L-arginine pool for NO production in neighboring neurons, we suggest a regulatory function for Bj-PRO-10c on the metabolism of this gaseous neurotransmitter in the CNS. Moreover, proliferation of astroglial cells was reduced in the presence of Bj-PRO-10c; however, cell death was not induced. Since NO donors have been studied for the treatment of solid cancers, Bj-PRO-10c may serve as structural model for developing drugs to improve the effects of cancer therapy based on the peptide's ability to augment NO production.

[Urea cycle enzymes in rats fed with corn]. / Enzimas del ciclo de la urea en ratas alimentadas con maíz.

Activities of five urea cycle enzymes, carbamyl phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinase and arginase, were measured in liver of rats fed two types of diet: diet I: raw common corn and, diet II: made of a mixture of corn starch ("maicena"), "chuño (dried potato), sugar and fat. The activities obtained were compared with those of a group of control rats fed a balanced diet with an adequate protein content. Diets were administered after weaning, through an experimental period of 90 days, and enzymatic activities were measured at regular intervals during this time. Animals raised on diet I as well as those raised on diet II, showed low activity of the five urea cycle enzymes, but the decrease of enzymatic activity was more pronounced and appeared earlier in animals raised on diet II. Carbamyl phosphate synthetase and argininosuccinate synthetase, the two synthetases of this cycle, decreased earlier and in a greater degree than the other three enzymes in animals raised on these two types of diet.