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Inhibitory effect of alpha-lipoic acid on mitochondrial dysfunction and interleukin-8 expression in interleukin-1beta-stimulated ataxia teleangiectasia fibroblasts.
- Source :
-
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society [J Physiol Pharmacol] 2020 Feb; Vol. 71 (1). Date of Electronic Publication: 2020 Jun 13. - Publication Year :
- 2020
-
Abstract
- Ataxia telangiectasia (A-T) is an inherited neurodegenerative disease caused by mutation in the ataxia telangiectasia mutated (ATM) gene, leading to loss of function in the encoded protein ATM. Because ATM functions to reduce oxidative stress by up-regulating antioxidant enzymes, oxidative stress is a prevalent A-T phenotype and a mediator of the inflammation that drives A-T pathology. Reactive oxygen species (ROS) levels and the expression of pro-inflammatory cytokine interleukin-8 (IL-8) were higher in A-T cells than in normal cells. ROS are related to mitochondrial dysfunction and activation of nuclear factor kappa B (NF-κB) to induce IL-8 expression. Alpha-lipoic acid (α-LA), a naturally occurring thiol compound, shows an antioxidant effect in various cells. This study is aimed to determine if α-LA confers protection against NF-κB activation, IL-8 expression, and mitochondrial dysfunction in A-T cells which are exposed to the inflammatory cytokine IL-1β. A-T fibroblasts were treated with or without α-LA. The levels of intracellular and mitochondrial ROS, mRNA and protein levels of IL-8, mitochondrial membrane potential (MMP), ATP levels, and DNA binding activity of NF-κB were determined. As a result, IL-1β increased NF-κB activation, IL-8 expression, intracellular and mitochondrial ROS levels, but decreased MMP and ATP level in A-T cells. Pretreatment of A-T cells with α-LA inhibited IL-1β-induced activation of NF-κB, IL-8 expression, and mitochondrial dysfunction by reducing ROS levels. In conclusion, supplementation with α-LA may be beneficial for reducing the oxidative stress-induced mitochondrial dysfunction and IL-8 production associated with A-T.
- Subjects :
- Antioxidants pharmacology
Ataxia Telangiectasia genetics
Ataxia Telangiectasia pathology
Cell Line
Fibroblasts drug effects
Fibroblasts pathology
Gene Expression
Humans
Interleukin-8 antagonists & inhibitors
Interleukin-8 genetics
Mitochondria drug effects
Mitochondria pathology
Reactive Oxygen Species metabolism
Ataxia Telangiectasia metabolism
Fibroblasts metabolism
Interleukin-1beta pharmacology
Interleukin-8 biosynthesis
Mitochondria metabolism
Thioctic Acid pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1899-1505
- Volume :
- 71
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of physiology and pharmacology : an official journal of the Polish Physiological Society
- Publication Type :
- Academic Journal
- Accession number :
- 32554850
- Full Text :
- https://doi.org/10.26402/jpp.2020.1.15