Sulfite

Sulfite protects neurons from oxidative stress

Our present data have shown sulfite to be a novel cytoprotective molecule against oxytosis, through maintaining cysteine levels in the extracellular milieu, leading to increased intracellular cysteine and GSH. Although there may be adverse clinical effects in sensitive individuals, our results provide a new insight into the therapeutic application of sulfite to neuronal diseases caused by oxidative stress.

Free sulfite, present at approximately 2 μM in the rat brain, converts cystine to cysteine more efficiently than H₂S and H₂Sn and facilitates transport of cysteine into cells.

Physiological concentrations of sulfite protected neurons from oxytosis and were accompanied by increased intracellular concentrations of cysteine and GSH probably due to converting extracellular cystine to cysteine, more efficiently than H₂S and H₂Sn. In contrast, thiosulfate only slightly protected neurons from oxytosis. (R1)

SUOX deficiency secondary to MoCo deficiency

the catabolism anomaly of sulfite to sulfate caused by sulfite oxidase or cofactor molybdenum deficiency (MoCD) is a rare metabolic disorder in which neurological damage is similar to that found in neonatal asphyxia. … The initial biological assessment found an elevated blood lactate level and the chromatography of amino acids showed a significant decrease of cystine and the abnormal presence of sulfocysteine, suggestive of a lack of sulfite oxidase activity. The uric acid level measured secondarily was low, suggesting a MoCD. (R2)

Lab findings

• Elevated blood lactate
• Decrease in Cystine
• Presence of Sulfocysteine
• Low Uric acid

Inhibits mitochondria biogenesis by lowering nuclear PGC1a

The effects of sulfite and bezafibrate (30 mg/kg/day) on the nuclear content of PGC-1α, the major regulator of mitochondrial biogenesis, were also evaluated once sulfite reduced mitochondrial mass and bezafibrate prevented this effect. It can be observed in Fig. 7 that sulfite decreased the nuclear PGC-1α immunocontent and that bezafibrate totally prevented this alteration (R4)

Disrupts brain mitochondrial energy homeostasis

It was verified that sulfite per se, but not thiosulfate, decreased state 3, CCCP-stimulated state and respiratory control ratio in mitochondria respiring with glutamate plus malate. In line with this, we found that sulfite inhibited the activities of glutamate and malate (MDH) dehydrogenases.

In addition, sulfite decreased the activity of a commercial solution of MDH, that was prevented by antioxidants and dithiothreitol. Sulfite also induced mitochondrial swelling and reduced mitochondrial membrane potential, Ca2 + retention capacity, NAD(P)H pool and cytochrome c immunocontent when Ca2 + was present in the medium. (R5)

Effect of sulfite on enzymes

• Reduces activity of Citrate Synthase (R4)
• Reduces activity of the supercomplex I-III (without altering II, II-III and IV) (R4)
• Reduces activity of Creatine Kinase (R4)
• Increases activity of Malate Dehydrogenase (R4). Conflicting results: Inhibits MDH (R5)
• Decreases GSH level (R4)
• Reduces activity of GPx (R4)
• Reduces activity of Glutathione Reductase (R4)
• Reduces activity of GST (R4)
• Reduces activity of G6PDH (R4)
• Increases activity of Catalase (R4)
• Inhibits Glutamate Dehydrogenase (R5)
• Increases S100B (R4)
• Increases GFAP (R4)

Sulfite doesn’t alter LC3B, suggesting it doesn’t cause autophagy

Sulfite did not alter acridine orange staining (Fig. 6B) and LC3B levels (Fig. 6C), suggesting that this metabolite does not cause autophagy. (R4).

Open questions

• Why Lactic acid is elevated in SUOX deficiency?
• Why Uric acid is low?
• Why cystine is low?