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- Name help_outline N-acetyl-L-cysteine Identifier CHEBI:78236 Charge -1 Formula C5H8NO3S InChIKeyhelp_outline PWKSKIMOESPYIA-BYPYZUCNSA-M SMILEShelp_outline CC(=O)N[C@@H](CS)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 9 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline L-glutamate Identifier CHEBI:29985 (CAS: 11070-68-1) help_outline Charge -1 Formula C5H8NO4 InChIKeyhelp_outline WHUUTDBJXJRKMK-VKHMYHEASA-M SMILEShelp_outline [NH3+][C@@H](CCC([O-])=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 249 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:74567 | RHEA:74568 | RHEA:74569 | RHEA:74570 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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N-acetylcysteine, xCT and suppression of Maxi-chloride channel activity in human placenta.
Lofthouse E.M., Manousopoulou A., Cleal J.K., O'Kelly I.M., Poore K.R., Garbis S.D., Lewis R.M.
<h4>Introduction</h4>Placental oxidative stress features in pregnancy pathologies but in clinical trials antioxidant supplementation has not improved outcomes. N-acetylcysteine (NAC) stimulates glutathione production and is proposed as a therapeutic agent in pregnancy. However, key elements of N-a ... >> More
<h4>Introduction</h4>Placental oxidative stress features in pregnancy pathologies but in clinical trials antioxidant supplementation has not improved outcomes. N-acetylcysteine (NAC) stimulates glutathione production and is proposed as a therapeutic agent in pregnancy. However, key elements of N-acetylcysteine biology, including its cellular uptake mechanism, remains unclear. This study explores how the cystine/glutamate transporter xCT may mediate N-acetylcysteine uptake and how N-acetylcysteine alters placental redox status.<h4>Methods</h4>The involvement of xCT in NAC uptake by the human placenta was studied in perfused placenta and Xenopus oocytes. The effect of short-term N-acetylcysteine exposure on the placental villous proteome was determined using LC-MS. The effect of N-acetylcysteine on Maxi-chloride channel activity was investigated in perfused placenta, villous fragments and cell culture.<h4>Results</h4>Maternoplacental N-acetylcysteine administration stimulated intracellular glutamate efflux suggesting a role of the exchange transporter xCT, which was localised to the microvillous membrane of the placental syncytiotrophoblast. Placental exposure to a bolus of N-acetylcysteine inhibited subsequent activation of the redox sensitive Maxi-chloride channel independently of glutathione synthesis. Stable isotope quantitative proteomics of placental villi treated with N-acetylcysteine demonstrated changes in pathways associated with oxidative stress, apoptosis and the acute phase response.<h4>Discussion</h4>This study suggests that xCT mediates N-acetylcysteine uptake into the placenta and that N-acetylcysteine treatment of placental tissue alters the placental proteome while regulating the redox sensitive Maxi-chloride channel. Interestingly N-acetylcysteine had antioxidant effects independent of the glutathione pathway. Effective placental antioxidant therapy in pregnancy may require maintaining the balance between normalising redox status without inhibiting physiological redox signalling. << Less
Placenta 110:46-55(2021) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.