Long-term dietary supplementation with cystathionine improves tissue glutathione in ageing rats.

BACKGROUND: Ageing is associated with decrease in tissue glutathione that can be reduced by food fortification with the amino acid cysteine. However, cysteine is not stable in solution and generates bad taste. Cystathionine, the direct precursor of cysteine, could be a valuable alternative. AIMS: This study aimed to determine whether long-term dietary supplementation with cystathionine induces an increase in glutathione pools. METHODS: Aged rats (20.5-month-old) were fed ad libitum during 29 weeks with either a cystathionine-supplemented diet (7.3 g/kg, n = 90 rats) or a control iso-nitrogenous alanine-supplemented diet (2.9 g/kg, n = 90 rats). RESULTS: Cystathionine was detected in the plasma of the cystathionine-supplemented rats but not in the control alanine-supplemented rats. Cystathionine increased glutathione concentrations in liver, small intestine and gastrocnemius muscle (P < 0.03). No adverse effect was observed. CONCLUSION: Cystathionine supplementation being able to increase moderately glutathione in healthy old rats could be considered as a candidate for nutritional supports aiming to revert the stronger glutathione depletions occurring in unhealthy elderly.

L-cystathionine inhibits oxidized low density lipoprotein-induced THP-1-derived macrophage inflammatory cytokine monocyte chemoattractant protein-1 generation via the NF-κB pathway.

This study aimed to explore whether and how L-cystathionine had any regulatory effect on the inflammatory response in THP-1-derived macrophages cultured in vitro under oxidized low-density lipoprotein (ox-LDL) stimulation. The human monocyte line THP-1 cell was cultured in vitro and differentiated into macrophages after 24 hours of PMA induction. Macrophages were pretreated with L-cystathionine and then treated with ox-LDL. The results showed that compared with the controls, ox-LDL stimulation significantly upregulated the expression of THP-1-derived macrophage MCP-1 by enhancing NF-κB p65 phosphorylation, nuclear translocation and DNA binding with the MCP-1 promoter. Compared with the ox-LDL group, 0.3 mmol/L and 1.0 mmol/L L-cystathionine significantly inhibited the expression of THP-1-derived macrophage MCP-1. Mechanistically, 0.3 mmol/L and 1.0 mmol/L L-cystathionine suppressed phosphorylation and nuclear translocation of the NF-κB p65 protein, as well as the DNA binding activity and DNA binding level of NF-κB with the MCP-1 promoter, which resulted in a reduced THP-1-derived macrophage MCP-1 generation. This study suggests that L-cystathionine could inhibit the expression of MCP-1 in THP-1-derived macrophages induced by ox-LDL via inhibition of NF-κB p65 phosphorylation, nuclear translocation, and binding of the MCP-1 promoter sequence after entry into the nucleus.

The effects of chronic isoniazid intoxication on motor end plate sprouting in rat sternocostalis muscle and on responses to partial denervation and local botulinum toxin.

Chronic dosing of rats with isoniazid (INH) leads to an increase in the incidence of short "spontaneous" sprouts on motor end plates in the rat sternocostalis muscle. After partial denervation there is a slight increase in terminal sprouting after 1 week of dosing: this changes to a significant decrease from 2 to 6 weeks of dosing. The same is noted after local botulinum toxin injection, and in both conditions sprout length is significantly reduced. In vitro studies show that glutathione, cysteine and cystathionine all increase the incidence of short, "spontaneous" sprouts from end plates, while homocysteine and cystine have no effect. These findings are interpreted in the light of the hypothesis that in INH intoxication there may be a reduction of available axonal glutathione and cysteine due to inhibition of the pyridoxal phosphate-dependent enzymes cystathionine synthetase and cystathioninase .

Enhanced cystathionine beta-lyase activity in transgenic potato plants does not force metabolite flow towards methionine.

Cystathionine beta-lyase (CbL) catalyses the second step in higher-plant methionine biosynthesis. To further characterise the role of CbL in methionine biosynthesis, transgenic potato (Solanum tuberosum L.) plants were generated that express a potato cystathionine beta-lyase (StCbL; EC 4.4.1.8) under the control of the cauliflower mosaic virus 35 S promoter. Transgenic potato lines showed no visible phenotype but revealed an accumulation of both CbL transcript and protein. The enzymatic activity of CbL in these lines was up to 2.5-fold higher than that of wild-type plants. GC-MS measurements of aspartate-derived metabolites, however, showed no significant changes in content of amino acids and pathway intermediates when transgenic and wild-type plants were compared. CbL over-expression did not change the expression patterns and gene products of other pathway-relevant genes as evident from RNA and protein blot analyses. Despite the essential role of CbL in plant growth and development, the data presented indicate that the homologous over-expression of CbL is not in itself able to enhance metabolic flux towards methionine biosynthesis.