Acetyl-CoA synthesized from glucose-derived pyruvate by pyruvate dehydrogenase complex (PDHC) is a main substrate, for mitochondrial energy production and cytoplasmic synthetic pathways in all types of brain cells. Activities of mitochondrial PDHC, and several enzymes of acetyl-CoA metabolism, and ZnT1 transporter level in cholinergic septal SN56 cells were from 2 to 8 times higher than those in microglial (N9) or astroglial (C6) cells. Differentiated cholinergic SN56 cells were highly susceptible to various neurotoxic signals: Zn, amyloid-β or NO excess. They decreased their viability and acetyl-CoA/ATP contents, due to inhibition or inactivation of PDHC and other enzymes of energy metabolism. Such conditions suppressed synthesis of acetyl-CoA, Nacetyl-L-aspartate, acetylcholine as well as its quantal release. Significant correlations existed between mitochondrial acetyl-CoA levels and SN56 viability in those conditions. On the other hand, nondifferentiated SN56, microglial (N9) or astroglial (C6) cells were more resistant to same detrimental insults. SN56 cells were resistant to high concentrations of lipopolysaccharide (LPS). On the contrary, in N9 cells low concentrations of LPS caused several-fold activation of NO and IL-6 and TNF-α synthesis/release, along with inhibition of PDHC, KDHC and aconitase activities yielding depression of acetyl-CoA, ATP contents but relatively small losses in their viability. Also, Zn and NO caused relatively weak inhibition enzymes of energy metabolism in N9 and C6 cells. Lipoic acid and L-carnitine rescued cells by preventing inhibition some of those enzymes by neurotoxins and alleviating acetyl-CoA and ATP deficits. Presented data indicate that particular types of brain cells constitute compartments of different levels and rates of acetyl-CoA metabolism, variably influencing their functional properties and viability both under neurodegenerative and cytoprotective conditions. Supported by MN59, MN58, MN108, ST57 GUMed funds.
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