BACKGROUND AND AIMS: The syndrome of neuroacantocytosis, characterized by degeneration of basal ganglia, accumulation of iron in CNS structures and the presence of acantocytes in the blood, is combined with defect of the key CoA biosynthetic enzyme, pantothenate kinase (PANK). Administration of D-hopanthenic acid (HPA), a competitive inhibitor of PANK, can simulate this form of neurodegeneration when it is initiated by inducer of systemic inflammation. METHODS: Adult male Wistar rats treated intragastrically with carbonyl iron (225 mg/kg daily over one month) were administered with HPA intraperitoneally (200 mg/kg daily over the last week) and with E. coli lipopolysaccharide (LPS) (500 µg/kg for 24 h). RESULTS: It was found that the LPS caused a 3-fold decrease of blood plasma total iron in the HPA-treated group, oxidative stress was pronounced and redox-buffer erythrocyte capacity decreased. The levels of CoASH and acyl-CoA were reduced in the basal ganglia and hippocampus on intake of carbonyl iron and LPS, which was not potentiated by HPA. The LPS administration caused an increase in the level of GSH in the brain hemispheres due to activation of the glutathione reductase. In this situation, the Eh value diminished after HPA treatment. This was also observed in the hippocampus with an increase in reduced glutathione fraction. The neuroblastoma SN56 cell culture was used to show (in collaboration with the Depart. Labor Med., MU, Gdansk) that activation of CoASH biosynthesis and (or) its enhanced transport in the presence of succinate increased cell viability and biomembrane stability after exposure to rotenone due to intramitochondrial production of acetyl-CoA. CONCLUSIONS: The CoA-dependent mechanism of production of the acetyl-CoA can be a key one in formation of intracellular redox-potential (Fisher-Wellman et al. 2015, Biochem J) that can potentiate development of neurodegeneration via the erythron signal function and iron deposition.
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