RESUMEN
Glutamate (Glu) excitotoxicity, which accompanies brain ischemia or traumatic brain injury, is the leading mechanism of neuronal death. In the present work, we studied the effects of the peptides HFRWPGP (ACTH6-9PGP), KKRRPG, and PyrRP on the survival of cultured cortical neurons on the background of excitotoxic effect of Glu (100 µM). Biochemical (MTT/WST) and morphometric analyzes showed that, depending on the dose, ACTH6-9PGP and KKRRPGP protect neurons from the cells death, while PyrRP, conversely, enhances it. The neuroprotective effect of ACTH6-9PGP is accompanied by a slowdown in the development of delayed calcium dysregulation and synchronous mitochondrial depolarization. Among the studied peptides, only ACTH6-9PGP significantly increased the number of neurons that restored Ca2+ homeostasis after Glu was abolished. The influence of KKRRPGP was less pronounced, whereas PyrRP, on the contrary, reduced the number of neurons with low [Ca2+]i. Thus, this study revealed the high therapeutic significance of ACTH6-9PGP and allowed assessing the prospects for its possible clinical use.
Asunto(s)
Calcio/metabolismo , Ácido Glutámico/química , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Péptidos/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Homeostasis , Potencial de la Membrana Mitocondrial , Microscopía Fluorescente , Mitocondrias/metabolismo , Oligopéptidos/química , Péptidos/química , Ratas , Ratas WistarRESUMEN
We studied the effect of collagen fragments (PGP and AcPGP) on serum content of epinephrine, corticosterone, and IL-1ß in rats subjected to water-immersion stress. The degree of local inflammation accompanying ulceration was assessed by IL-1ß production by ln. gastricus caudalis cells. In 1 h, the sharp increase in hormone concentrations in the blood of stressed animals reflected the high stress intensity. Intranasal administration of PGP reduced the area of stress-induced ulcers by 63%, prevented the increase in the levels of stress hormones and the main proinflammatory cytokine in rat blood. The concentrations of IL-1ß in cell culture from regional lymph node of experimental animals returned to normal in 24 and 48 h after the stress. Acetylation of PGP prevents with gastroprotection, but does not abrogate other properties of the peptide.