måndag 23 november 2015

Miten myrkyllinen sulfiitti on aivolle . Sulfiittioksidaasin puute.

  • Miten myrkyllinen on sulfiitti?
Biochim Biophys Acta. 2014 Sep;1842(9):1413-22. doi: 10.1016/j.bbadis.2014.04.022. Epub 2014 May 2.
Sulfite disrupts brain mitochondrial energy homeostasis and induces mitochondrial permeability transition pore opening via thiol group modification.
Grings M1, Moura AP1 et al.
Sulfite oxidase (SO) deficiency is biochemically characterized by the accumulation of sulfite, thiosulfate and S-sulfocysteine in tissues and biological fluids of the affected patients. The main clinical symptoms include severe neurological dysfunction and brain abnormalities, whose pathophysiology is still unknown. The present study investigated the in vitro effects of sulfite and thiosulfate on mitochondrial homeostasis in rat brain mitochondria. 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, Ca(2+) retention capacity, NAD(P)H pool and cytochrome c immunocontent when Ca(2+) was present in the medium.
 These alterations were prevented by ruthenium red, cyclosporine A (CsA) and ADP, supporting the involvement of mitochondrial permeability transition (MPT) in these effects. We further observed that N-ethylmaleimide prevented the sulfite-elicited swelling and that sulfite decreased free thiol group content in brain mitochondria. These findings indicate that sulfite acts directly on MPT pore containing thiol groups.
 Finally, we verified that sulfite reduced cell viability in cerebral cortex slices and that this effect was prevented by CsA. Therefore, it may be presumed that disturbance of mitochondrial energy homeostasis and MPT induced by sulfite could be involved in the neuronal damage characteristic of SO deficiency. 

Kommentti 23.11. 2015 
Sulfiittioksidaasi on mitokondriaalinen entsyymi, josa on hemi ja molybdeenidomaani. Sen geeni on SUOX Kr. 12q13.2. 
oksidaasi redusoi sulfiitin sulfaatiksi ja nitriitin NO:ksi. 

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