Pantothenic acid in maintaining thiol and immune homeostasis

Мойсеенок, А. Г.; Komar, Véronique; Хомич, Т. И.; Канунникова, Н. П.; Slyshenkov, Vyacheslav S.

doi:10.1002/biof.5520110115

Cited by 15 publications

(11 citation statements)

References 6 publications

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“…These nutrients are involved in multiple essential metabolic functions, including intermediary metabolism, protein synthesis, bone density and brain and immune function (Bonjour 1980; Uchida et al . 2015; Moiseenok et al 2000; Palaniyappan and Alphonese 2011). Thus, it is not surprising that a decrease in cellular availability (i. e., cellular deficiency) of these nutrients leads to disturbance in normal cellular metabolism/function and ultimately to disease manifestations.…”

Section: Discussionmentioning

confidence: 99%

“…1998; Wolf 2001); systemic pantothenic acid deficiency leads to deficiency of CoA production (Martinez et al . 2014) and neuro-degeneration and immune dysfunction (Moiseenok et al 2000; Follis and Wintrobe 1945; Kuo et al . 2007); systemic lipoate deficiency leads to immune modulation and slowed cell growth and differentiation (Palaniyappan and Alphonese 2011; Bilska and Wlodek 2005; Li et al 2014; Cui et al 2009) and loss of bone density (Roberts and Moreau 2015).…”

Section: Discussionmentioning

confidence: 99%

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Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child

et al. 2016

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The human sodium-dependent multivitamin transporter (hSMVT) is a product of the SLC5A6 gene and mediates biotin, pantothenic acid and lipoate uptake in a variety of cellular systems. We report here the identification of mutations R94X, a premature termination, and R123L, a dysfunctional amino acid change, both in exon 3 of the SLC5A6 gene in a child using whole genome-scanning. At 15 months of age, the child showed failure to thrive, microcephaly and brain changes on MRI, cerebral palsy and developmental delay, variable immunodeficiency, severe gastro-esophageal reflux requiring a gastrostomy tube/fundoplication, osteoporosis and pathologic bone fractures. After identification of the SLC5A6 mutations, he responded clinically to supplemental administration of excess biotin, pantothenic acid and lipoate with improvement in clinical findings. Functionality of the two mutants was examined by 3H-biotin uptake assay following expression of the mutants in human-derived intestinal HuTu-80 and brain U87 cells. The results showed severe impairment in biotin uptake in cells expressing the mutants compared to those expressing wild-type hSMVT. Live cell confocal imaging of cells expressing the mutants showed the R94X mutant to be poorly tolerated and localized in the cytoplasm, while the R123L mutant was predominantly retained in the endoplasmic reticulum. This is the first reporting of mutations in the SLC5A6 gene in man, and suggests that this gene is important for brain development and a wide variety of clinical functions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child

et al. 2016

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“…Accordingly, we found that, when applied to isolated mitochondria, the reduced form pantetheine was able to preserve complex I activity, and therefore to maintain complex I redox status; the oxidized form pantethine did not. It should be underlined that GSH and CoA levels, as well as complex I activity and ATP production are interdependent and their interactions remain to be clarified [42,43]. …”

Section: Discussionmentioning

confidence: 99%

Enhancement of L-3-hydroxybutyryl-CoA dehydrogenase activity and circulating ketone body levels by pantethine. Relevance to dopaminergic injury

et al. 2010

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BackgroundThe administration of the ketone bodies hydroxybutyrate and acetoacetate is known to exert a protective effect against metabolic disorders associated with cerebral pathologies. This suggests that the enhancement of their endogenous production might be a rational therapeutic approach. Ketone bodies are generated by fatty acid beta-oxidation, a process involving a mitochondrial oxido-reductase superfamily, with fatty acid-CoA thioesters as substrates. In this report, emphasis is on the penultimate step of the process, i.e. L-3-hydroxybutyryl-CoA dehydrogenase activity. We determined changes in enzyme activity and in circulating ketone body levels in the MPTP mouse model of Parkinson's disease. Since the active moiety of CoA is pantetheine, mice were treated with pantethine, its naturally-occurring form. Pantethine has the advantage of being known as an anti-inflammatory and hypolipidemic agent with very few side effects.ResultsWe found that dehydrogenase activity and circulating ketone body levels were drastically reduced by the neurotoxin MPTP, whereas treatment with pantethine overcame these adverse effects. Pantethine prevented dopaminergic neuron loss and motility disorders. In vivo and in vitro experiments showed that the protection was associated with enhancement of glutathione (GSH) production as well as restoration of respiratory chain complex I activity and mitochondrial ATP levels. Remarkably, pantethine treatment boosted the circulating ketone body levels in MPTP-intoxicated mice, but not in normal animals.ConclusionsThese finding demonstrate the feasibility of the enhancement of endogenous ketone body production and provide a promising therapeutic approach to Parkinson's disease as well as, conceivably, to other neurodegenerative disorders.

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“…Beneficial effects of precursors of CoA biosynthesis, such as pantothenic acid and its derivatives, include protection from lipoperoxidation and supporting membrane structure, and these effects have been observed in radiation injury, miocard ischemia, diabetes mellitus, CCl4 -intoxication, heavy hypothermia, etc [103][104][105][106]. Protective action of pantothenate derivatives have been reported in situations accompanied by oxidative stress, for example, in experimental ischemia-reperfusion of myocardium.…”

Section: Role Of Coa In Mechanisms Of Neuroprotection In Brain Ischemmentioning

confidence: 99%

“…It is believed that the physiological function of CoA system is participation in formation of redox potential of glutathione and proteins, redox signaling and maintenance of biological membrane stability, especially in brain tissue [104,105,106].…”

Section: Role Of Coa In Mechanisms Of Neuroprotection In Brain Ischemmentioning

confidence: 99%

Use of CoA Biosynthesis Modulators and Selenoprotein Model Substance in Correction of Brain Ischemic and Reperfusion Injuries

Канунникова¹,

Башун²,

Мойсеенок³

2012

Lipid Peroxidation

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Pantothenic acid in maintaining thiol and immune homeostasis

Cited by 15 publications

References 6 publications

Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child

Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child

Enhancement of L-3-hydroxybutyryl-CoA dehydrogenase activity and circulating ketone body levels by pantethine. Relevance to dopaminergic injury

Use of CoA Biosynthesis Modulators and Selenoprotein Model Substance in Correction of Brain Ischemic and Reperfusion Injuries

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