Putative Significance of Shifts in Acetyl-CoA Compartmentalization in Nerve Terminals for Disturbances of Cholinergic Transmission in Brain

Szutowicz, Andrzej; Tomaszewicz, Maria; Bielarczyk, Hanna; Jankowska, Agnieszka

doi:10.1159/000017347

Cited by 20 publications

(32 citation statements)

References 31 publications

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“…The mitochondrial pathway was even stimulated (Fig. 7), but this might be due to an isotope effect as during thiamine deficiency acetyl-CoA levels are lowered [36].…”

Section: Resultsmentioning

confidence: 99%

Thiamine pyrophosphate: An essential cofactor for the α-oxidation in mammals – implications for thiamine deficiencies?

Sniekers

Foulon

Mannaerts

et al. 2006

Cell. Mol. Life Sci.

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The identification of 2-hydroxyphytanoyl-CoA lyase (2-HPCL), a thiamine pyrophosphate (TPP)-dependent peroxisomal enzyme involved in the alpha-oxidation of phytanic acid and of 2-hydroxy straight chain fatty acids, pointed towards a role of TPP in these processes. Until then, TPP had not been implicated in mammalian peroxisomal metabolism. The effect of thiamine deficiency on 2-HPCL and alpha-oxidation has not been studied, nor have possible adverse effects of deficient alpha-oxidation been considered in the pathogenesis of diseases associated with thiamine shortage, such as thiamine-responsive megaloblastic anemia (TRMA). Experiments with cultured cells and animal models showed that alpha-oxidation is controlled by the thiamine status of the cell/tissue/organism, and suggested that some pathological consequences of thiamine starvation could be related to impaired alpha-oxidation. Whereas accumulation of phytanic acid and/or 2-hydroxyfatty acids or their alpha-oxidation intermediates in TRMA patients given a normal supply of thiamine is unlikely, this may not be true when malnourished.

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“…The mitochondrial pathway was even stimulated (Fig. 7), but this might be due to an isotope effect as during thiamine deficiency acetyl-CoA levels are lowered [36].…”

Section: Resultsmentioning

confidence: 99%

Thiamine pyrophosphate: An essential cofactor for the α-oxidation in mammals – implications for thiamine deficiencies?

Sniekers

Foulon

Mannaerts

et al. 2006

Cell. Mol. Life Sci.

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“…The AlPO 4 (OH) Ϫ was proposed to be a biologically active form of Al because its inhibitory effects on acetyl-CoA and ACh metabolism in nerve terminals were observed only in the medium containing phosphate. Al inhibited oxidation of glucose and pyruvate both in isolated nerve terminals and whole brain mitochondria as well as in cultured SN56 cholinergic neuroblastoma cells (Table I) (Bielarczyk et al, 1998;Szutowicz et al, 1998aSzutowicz et al, ,b, 2000Jankowska et al, 2000). It had, however, no direct inhibitory effect on PDH and KDH activities in disintegrated brain preparations (Zatta et al, 2000).…”

Section: Effects Of Aluminummentioning

confidence: 99%

Aluminum, NO, and nerve growth factor neurotoxicity in cholinergic neurons

Szutowicz

2001

J of Neuroscience Research

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Several neurotoxic compounds, including Al, NO, and beta-amyloid may contribute to the impairment or loss of brain cholinergic neurons in the course of various neurodegenerative diseases. Genotype and phenotypic modifications of cholinergic neurons may determine their variable functional competency and susceptibility to reported neurotoxic insults. Hybrid, immortalized SN56 cholinergic cells from mouse septum may serve as a model for in vitro cholinotoxicity studies. Differentiation by various combinations of cAMP, retinoic acid, and nerve growth factor may provide cells of different morphologic maturity as well as activities of acetylcholine and acetyl-CoA metabolism. In general, differentiated cells appear to be more susceptible to neurotoxic signals than the non-differentiated ones, as evidenced by loss of sprouting and connectivity, decreases in choline acetyltransferase and pyruvate dehydrogenase activities, disturbances in acetyl-CoA compartmentation and metabolism, insufficient or excessive acetylcholine release, as well as increased expression of apoptosis markers. Each neurotoxin impaired both acetylcholine and acetyl-CoA metabolism of these cells. Activation of p75 or trkA receptors made either acetyl-CoA or cholinergic metabolism more susceptible to neurotoxic influences, respectively. Neurotoxins aggravated detrimental effects of each other, particularly in differentiated cells. Thus brain cholinergic neurons might display a differential susceptibility to Al and other neurotoxins depending on their genotype or phenotype-dependent variability of the cholinergic and acetyl-CoA metabolism.

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“…In cholinergic nerve terminals, aluminium leads to severe impairment of the quantal transmitter pool [143][144][145]. However, the mechanism of action is not completely understood.…”

Section: Triggered Release Of Neurotransmittersmentioning

confidence: 99%