Abstract
The physiological roles of taurine, a product of cysteine degradation and one of the most abundant amino acids in the body, remain elusive. Taurine deficiency leads to heart dysfunction, brain development abnormalities, retinal degradation, and other pathologies. The taurine synthetic pathway is proposed to be incomplete in astrocytes and neurons, and metabolic cooperation between these cell types is reportedly needed to complete the pathway. In this study, we analyzed taurine synthesis capability as reported by incorporation of radioactivity from [(35)S]cysteine into taurine, in primary murine astrocytes and neurons, and in several transformed cell lines (human (SH-SY5Y) and murine (N1E-115) neuroblastoma, human astrocytoma (U-87 MG and 1321 N1), and rat glioma (C6)). Extensive incorporation of radioactivity from [(35)S]cysteine into taurine was observed in rat glioma cells as well as in primary mouse astrocytes and neurons, establishing the presence of an intact taurine synthesis pathway in these cells. Interestingly, exposure of cells to cysteine or cysteamine resulted in elevated intracellular hypotaurine without a corresponding increase in taurine levels, suggesting that oxidation of hypotaurine limits taurine synthesis in cells. Consistent with its role as an organic osmolyte, taurine synthesis was stimulated under hypertonic conditions in neurons.
Highlights
It is generally believed that taurine cannot be further metabolized and is excreted by the kidney or as a bile component, there are several older reports in the literature on the conversion of taurine to isethionic acid in mammalian tissues
Cysteamine and Cystamine Increase Hypotaurine but Not Taurine Levels in Transformed Human Brain-derived Cell Lines—In preliminary experiments, we have found that incubation of human astrocytoma (U-87 MG) and neuroblastoma (SH-SY5Y) cells with varying concentrations of cysteamine or its oxidized disulfide form, cystamine, results in an approximately 2- to 4-fold increase in intracellular hypotaurine concentrations (Fig. 2)
The Pathway for Oxidation of Cysteine to Taurine Is Intact in Primary Astrocytes and Neurons but Is Not Uniformly Preserved in Transformed Cell Lines—we examined whether the pathway for taurine biosynthesis from cysteine is intact in several brain-derived transformed cell lines
Summary
Exposure of cells to cysteine or cysteamine resulted in elevated intracellular hypotaurine without a corresponding increase in taurine levels, suggesting that oxidation of hypotaurine limits taurine synthesis in cells. Its biosynthesis involves the sequential oxidation of cysteine to cysteinesulfinic acid, catalyzed by cysteine dioxygenase, decarboxylation by cysteinesulfinate decarboxylase, and oxidation of the resulting hypotaurine to taurine by a putative hypotaurine dehydrogenase (Fig. 1) The latter enzyme has, not been purified to homogeneity and remains uncharacterized [1,2,3]. These results were interpreted as evidence for intercellular metabolic coupling, i.e. the presence of neurons modulates the hypotaurine:taurine ratio in astrocytes, whereas the presence of astrocytes increases neuronal taurine content These labeling studies were performed with supraphysiological concentrations of cysteine rather than the relevant extracellular form of this amino acid, cystine, raising questions about their biological relevance [23]. Labeling rat astrocytes with [13C]cysteine results in labeling of
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