Thiotaurine Protects Mouse Cerebellar Granule Neurons from Potassium Deprivation-Induced Apoptosis by Inhibiting the Activation of Caspase-3

Abstract

Taurine (2-aminoethanesulphonic acid) is an endogenous amino acid that has a number of protective roles in most mammalian cells, including modulation of cytoplasmic calcium levels, antioxidant effects and protection against mitochondrial dysfunction and endoplasmic reticulum stress associated with neurological disorders. Thiotaurine (2-aminoethane thiosulfonate), a molecule structurally related to hypotaurine and taurine, counteracts the damaging effect of oxidants and prevents apoptosis of human neutrophils.

In this study we have compared the effect of taurine and thiotaurine in protecting cerebellar granule neurons (CGNs) from apoptotic death. Two experimental paradigms were exploited to induce apoptosis: i) CGNs were continuously cultured in 5 mM K⁺-containing medium up to 6 days in the presence or absence of 1 mM either taurine or thiotaurine (chronic paradigm); ii) CGNs were cultured in 25 mM K⁺-containing medium for 6 days and then shifted to a 5 mM K⁺-containing medium in the presence or absence of 1 mM either taurine or thiotaurine (acute paradigm). In the first condition, CGNs survive up to 5 days, and then start to die; in the second condition, CGNs nicely differentiate elongating neurites but enter apoptosis within 30 min when shifted to the 5 mM K⁺-containing medium.

These assays showed that taurine and thiotaurine counteracted the apoptotic death induced by low potassium in both the acute and chronic paradigms. However, while they displayed a similar efficacy in the chronic paradigm, the thiotaurine showed a significantly higher (20 %) efficacy compared to taurine in the acute paradigm. This finding pinpoints the thiotaurine as a powerful anti-apoptotic molecule in neurons that are fully differentiated and have established synaptic connections.