Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production

Abstract

An important function of the β-amino acid, taurine, is the regulation of oxidative stress. However, taurine is neither a classical scavenger nor a regulator of the antioxidative defenses, leaving uncertain the mechanism underlying the antioxidant activity of taurine. In the present study, the taurine antagonist and taurine transport inhibitor, β-alanine, was used to examine the mechanism underlying the antioxidant activity of taurine. Exposure of isolated cardiomyocytes to medium containing β-alanine for a period of 48 h led to a 45% decrease in taurine content and an increase in mitochondrial oxidative stress, as evidenced by enhanced superoxide generation, the inactivation of the oxidant sensitive enzyme, aconitase, and the oxidation of glutathione. Associated with the increase in oxidative stress was a decline in electron transport activity, with the activities of respiratory chain complexes I and III declining 50-65% and oxygen consumption falling 30%. A reduction in respiratory chain activity coupled with an increase in oxidative stress is commonly caused by the development of a bottleneck in electron transport that leads to the diversion of electrons from the respiratory chain to the acceptor oxygen forming in the process superoxide. Because β-alanine exposure significantly reduces the levels of respiratory chain complex subunits, ND5 and ND6, the bottleneck in electron transport appears to be caused by impaired synthesis of key subunits of the electron transport chain complexes. Co-administration of taurine with β-alanine largely prevents the mitochondrial effects of β-alanine, but treatment of the cells with 5 mM taurine in the absence of β-alanine has no effect on the mitochondria, likely because taurine treatment has little effect on cellular taurine levels. Thus, taurine serves as a regulator of mitochondrial protein synthesis, thereby enhancing electron transport chain activity and protecting the mitochondria against excessive superoxide generation.

Diet affects the redox system in developing Atlantic cod (Gadus morhua) larvae

“…Elevated concentrations of taurine are required in the mitochondria where its pH buffering capacity maintains optimum enzyme activity [44]. Taurine is also present in mitochondrial tRNA and thus is important for protein synthesis [44,45]. Taurine deficiency can result in mitochondrial oxidative stress in vitro [45], and rotifer-fed cod larvae have abnormal mitochondria in liver and intestinal cells (Elin Kjørsvik, personal communication).…”

“…Taurine is also present in mitochondrial tRNA and thus is important for protein synthesis [44,45]. Taurine deficiency can result in mitochondrial oxidative stress in vitro [45], and rotifer-fed cod larvae have abnormal mitochondria in liver and intestinal cells (Elin Kjørsvik, personal communication). We found that many genes important for maintaining the mitochondrial redox environment -nrf2, gpx1, sod2, prdx3, prdx5 and msrb2 [19,46,47] -were differentially regulated in rotifer-fed larvae.…”

Clinical significance of taurine

“…Biochemically, this enhances the binding of the UUG codon to the taurine-modified AAU anticodon of tRNA Leu(UUR) , facilitating UUG decoding. When the formation of 5-taurinomethyluridine-tRNA Leu(UUR) is abolished, the biosynthesis of certain mitochondria encoded proteins dramatically declines, respiratory function falls, ATP generation decreases and the generation of oxidants by the respiratory chain increases (Jong et al 2012;Schaffer et al 2013). Another important function of taurine is the detoxification of xenobiotics and the neutralization of toxic aldehydes (Miyazaki and Matsuzaki 2013).…”

“…One of the major biochemical abnormalities of the tRNA Leu(UUR) mutations is decreased formation of 5-taurinomethyluridine in the wobble position of tRNALeu(UUR) (Kirino et al 2005;Kurata et al 2008). Because taurine conjugation enhances the interaction of the UUG codon with the taurine-modified AAU anticodon of tRNA Leu(UUR) , the synthesis of mitochondria encoded proteins, such as ND6, is highly dependent upon the 5-taurinomethyluridine modification (Jong et al 2012). Hence, taurine deficiency and MELAS are both associated with complex I deficiency (Santa 2010;Jong et al 2012).…”

“…Because taurine conjugation enhances the interaction of the UUG codon with the taurine-modified AAU anticodon of tRNA Leu(UUR) , the synthesis of mitochondria encoded proteins, such as ND6, is highly dependent upon the 5-taurinomethyluridine modification (Jong et al 2012). Hence, taurine deficiency and MELAS are both associated with complex I deficiency (Santa 2010;Jong et al 2012). Because taurine deficiency and MELAS lead to a defect in taurine conjugation, it is possible that taurine therapy might partially restore 5-taurinomethyluridine-tRNA Leu(UUR) levels, thereby benefiting patients suffering from MELAS.…”