Volume 7, Number 3, p.p. 87–96
Lack of alteration in brain markers of apoptosis but increase in p53 in acute ammonia neurotoxicity
N.I. Venediktova, E.A. Kosenko, N.V. Marov, I.N. Solomadin and Y.G. Kaminsky*
Institute of Theoretical & Experimental Biophysics, Russian Academy of Sciences, 142290 Pushchino, Russia
The effects of acute ammonia intoxication in vivo on the brain metabolic indices known as pro-apoptotic markers were studied. Intraperitoneal injection of ammonium acetate in rats appeared to be not associated with either the induction of caspase-9 and caspase-3, a change of brain mitochondrial membrane potential, cytochrome c release from mitochondria to cytosol, or the induction of apoptosis signals in the nuclei. Mitochondrial and nuclear levels of p53 were unchanged while cytoplasmic p53 was increased in hyperammonaemia. The resistance of the nuclei to ammonia-induced apoptosis could be due to both the disturbed p53 translocation from the cytosol into the nuclei and a p53 transfer in an inactive form. Thus, no evidence was obtained for the functional significance of mitochondria in the cell death pathway in acute hyperammonaemia.
Keywords: ammonia toxicity, apoptosis, caspases, cytochrome c, brain mitochondria, brain nuclei, p53 protein