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RS‐α‐lipoic acid protects cholinergic cells against sodium nitroprusside and amyloid‐β neurotoxicity through restoration of acetyl‐CoA level
Author(s) -
Bielarczyk Hanna,
Gul Sylwia,
Ronowska Anna,
BizonZygmanska Dorota,
Pawelczyk Tadeusz,
Szutowicz Andrzej
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03966.x
Subject(s) - lipoic acid , choline acetyltransferase , pyruvate dehydrogenase complex , cholinergic neuron , mitochondrion , biochemistry , neurotoxicity , cholinergic , biology , neuroprotection , endocrinology , chemistry , medicine , enzyme , pharmacology , toxicity , antioxidant
The work presented here verifies the hypothesis that RS‐α‐lipoic acid may exert its cholinoprotective and cholinotrophic activities through the maintenance of appropriate levels of acetyl‐CoA in mitochondrial and cytoplasmic compartments of cholinergic neurons. Sodium nitroprusside (SNP) and amyloid‐β decreased pyruvate dehydrogenase, choline acetyltransferase activities, acetyl‐CoA content in mitochondria and cytoplasm, as well as increased fraction of non‐viable, trypan blue positive cells in cultured differentiated cholinergic SN56 neuroblastoma cells. Lipoic acid totally reversed toxin‐evoked suppression of choline acetyltrasferase and pyruvate dehydrogenase activities, as well as mitochondrial and cytoplasmic acetyl‐CoA levels, and partially attenuated increase of cell mortality. Significant negative correlations were found between enzyme activities, acetyl‐CoA levels and cell mortality in different neurotoxic and neuroprotective conditions employed here. The level of cytoplamic acetyl‐CoA correlated with mitochondrial acetyl‐CoA, whereas choline acetyltransferase activity followed shifts in cytoplasmic acetyl‐CoA. Thus, we conclude that, in cholinergic neurons, particular elements of the pyruvate–acetyl‐CoA–acetylcholine pathway form a functional unit responding uniformly to nerotoxic and neuroprotectory conditions.