Abstract
Primary cultures of rat astroglial cells were exposed to 1, 3 and 5 mM NH4Cl for up to 10 days. Dose- and time-dependent reductions in cell numbers were seen, plus an increase in the proportion of cells in the S phase. The DNA content was reduced in the treated cells, and BrdU incorporation diminished. However, neither ammonia nor ammonia plus glutamine had any effect on DNA polymerase activity. iTRAQ analysis showed that exposure to ammonia induced a significant reduction in histone and heterochromatin protein 1 expression. A reduction in cell viability was also noted. The ammonia-induced reduction of proliferative activity in these cultured astroglial cells seems to be due to a delay in the completion of the S phase provoked by the inhibition of chromatin protein synthesis.
Highlights
Metabolic ammonia is the main causal agent of hepatic encephalopathy (HE) [1]
It is logical to assume that cells growing under very low fetal bovine serum (FBS) content conditions might have a low proliferative rate, and that this might make it difficult to detect any effect of ammonia
Confluent astroglial cells were exposed to 5 mM NH4Cl for 10 days with either 0.5 or 5% FBS
Summary
Metabolic ammonia is the main causal agent of hepatic encephalopathy (HE) [1]. It has been suggested that ammonia might affect cerebral energy metabolism, neurotransmitter pathways, nitric oxide synthesis and signal transduction, and produce oxidative stress [2,3,4], but the exact pathological mechanisms underlying HE remain unknown.Astroglial cells play a pivotal role in ammonia metabolism [5]. Metabolic ammonia is the main causal agent of hepatic encephalopathy (HE) [1]. It has been suggested that ammonia might affect cerebral energy metabolism, neurotransmitter pathways, nitric oxide synthesis and signal transduction, and produce oxidative stress [2,3,4], but the exact pathological mechanisms underlying HE remain unknown. Astroglial cells play a pivotal role in ammonia metabolism [5]. Astroglial dysfunction might, lead to nerve cell disease [7]. The effects of ammonia on astroglial proliferation, have been little documented. The many changes in cell physiology induced by ammonia might have an effect on the cell cycle (which is normally carefully regulated), and on astroglial proliferation. In vivo studies showing ammonia-induced alterations of PLOS ONE | DOI:10.1371/journal.pone.0139619. In vivo studies showing ammonia-induced alterations of PLOS ONE | DOI:10.1371/journal.pone.0139619 September 30, 2015
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