Cysteine persulfides and polysulfides produced by exchange reactions with H2S protect SH-SY5Y cells from methylglyoxal-induced toxicity through Nrf2 activation

Autor: Shin Koike, Yuki Ogasawara, Shoichi Nishimoto
Rok vydání: 2017
Předmět:
0301 basic medicine
SH-SY5Y
TRPA1
transient receptor potential ankyrin 1
Clinical Biochemistry
AGEs
advanced glycation end products
BS-Mix
bound sulfur mixture
Biochemistry
Df
differentiated
chemistry.chemical_compound
RA
retinoic acid
Disulfides
Hydrogen Sulfide
lcsh:QH301-705.5
3MST
3-mercaptopyruvate sulfurtransferase
NaHS
sodium hydrogen sulfide
lcsh:R5-920
ESI
electrospray ionization
LDH
lactate dehydrogenase
mBB
monobromobimane
Na2S
sodium sulfide
Methylglyoxal
Pyruvaldehyde
Glutathione
Keap1
Kelch-like ECH-associated protein 1
DMB
1
2-diamino-4
5-methylenedioxybenzene
Bound sulfur species
NQO1
NAD (P) H: quinone oxidoreductase
lcsh:Medicine (General)
BSS
bound sulfur species
Intracellular
Research Paper
NF-E2-Related Factor 2
Cystine
Sulfides
CNS
central nervous system
Nrf2
H2S
hydrogen sulfide
Persulfide
03 medical and health sciences
Cell Line
Tumor
Nrf2
nuclear factor erythroid-2-related factor-2
Humans
Cysteine
Polysulfide
SSP4
sulfane sulfur probe 4
Organic Chemistry
GLO
glyoxalase
In vitro
Culture Media
030104 developmental biology
lcsh:Biology (General)
chemistry
DTT
dithiothreitol
MG
methylglyoxal
Zdroj: Redox Biology
Redox Biology, Vol 12, Iss, Pp 530-539 (2017)
ISSN: 2213-2317
DOI: 10.1016/j.redox.2017.03.020
Popis: Many physiological functions of hydrogen sulfide (H2S) have been reported in mammalian cells over the last 20 years. These physiological effects have been ascertained through in vitro treatment of cells with Na2S or NaHS, both of which are precursors of H2S. Since H2S exists as HS− in a neutral solution, a disulfide compound such as cystine could react with HS− in culture medium as well as in the cell. This study demonstrated that after the addition of Na2S solution into culture medium, HS− was transiently generated and disappeared immediately through the reaction between HS− and cystine to form cysteine persulfides and polysulfides in the culture medium (bound sulfur mixture: BS-Mix). Furthermore, we found that the addition of Na2S solution resulted in an increase of intracellular cysteine persulfide levels in SH-SY5Y cells. This alteration in intracellular persulfide was also observed in cystine-free medium. Considering this reaction of HS− as a precursor of BS-Mix, we highlighted the cytoprotective effect of Na2S on human neuroblastoma SH-SY5Y cells against methylglyoxal (MG)-induced toxicity. BS-Mix produced with Na2S in cystine-containing medium provided SH-SY5Y cells significant protective effect against MG-induced toxicity. However, the protective effect was attenuated in cystine-free medium. Moreover, we observed that Na2S or BS-Mix activated the Keap1/Nrf2 system and increased glutathione (GSH) levels in the cell. In addition, the activation of Nrf2 is significantly attenuated in cystine-free medium. These results suggested that Na2S protects SH-SY5Y cells from MG cytotoxicity through the activation of Nrf2, mediated by cysteine persulfides and polysulfides that were generated by Na2S addition.
Highlights • Neuronal cells were protected from methylglyoxal-induced toxicity by cysteine persulfides. • H2S immediately reacts with cystine to form persulfides and polysulfides in culture medium. • Cysteine persulfides protect neuronal cells from carbonyl stress through the activation of Nrf2.
Graphical abstract fx1
Databáze: OpenAIRE
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