RESUMO
A new type of bioactive polypeptides of the neurosecretory hypothalamus called prolinerich peptides (PRPs), which are isolated from bovine neurosecretory granules of the neurohypophysis, are synthesized in the form of a common precursor protein (neurophysin vasopressinassociated glycoprotein). Prolinerich polypetide 1 (PRP1; also known as galarmin) is comprised of 15 amino acids residues, and has been suggested to possess antineurodegenerative, immunoregulatory, hematopoietic, antimicrobial and antitumor properties. The cytostatic, antiproliferative effect of PRP1 was demonstrated in the human chondrosarcoma JJ012 and triple negative breast carcinoma MDA MB 231 cell lines. PRP1 action is disease and tissue specific. To further explore the antitumorigenic and possible cytotoxic effects of PRP1, a morphofunctional study on the effect of PRP1 on a mouse Ehrlich ascites carcinoma (EAC) model was conducted. The PRP1induced morphological features of EAC cells confirmed the apoptotic nature of PRP1, as manifested by cell shrinkage, membrane blebbing, chromosome condensation (pyknosis) and nuclear fragmentation (karyorrhexis). The effect of PRP1 on the number of tumor cells incubated for 24 h and their viability in trypan bluestained samples lead to a 44% reduction in the number of viable cells on day 11 postinoculation vs. 22% inhibition of viable cells after PRP1 treatment (0.1 µg/ml) on day 7 postinoculation. Apoptosis experiments using an Annexin Vcyanine 3 apoptosis detection kit indicated that 24 h incubation with 0.1 µg/ml PRP1 caused a significant increase in the number of apoptotic cells, reaching 50.33%, compared to 8.33% in the sample control on day 7 postinoculation.
Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Carcinoma de Ehrlich/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Animais , Peptídeos Catiônicos Antimicrobianos/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Bovinos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Masculino , Especificidade de Órgãos , Células Tumorais CultivadasRESUMO
A fragment (11-19) of thymosin beta 4 was found to stimulate phosphodiesterase activity even in the absence of calcium and calmodulin. Half-maximal enzyme activation occurred with 10 nM peptide, and was further increased by phospholipids such as phosphatidylserine. The mechanism of stimulation is an increase in the Vmax of cAMP degradation without a substantial change in the Km for the substrate. In the presence of calcium ions and calmodulin the peptide was also stimulatory.