Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.64 (
MPP
)
1,876
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The neurotoxin
MPP
+
(1-methyl-4-phenylpyridinium ion) disrupts mitochondrial function leading to oxidative stress and neuronal death. Here we examine whether activation of the Keap1-Nrf2 cascade can protect SH-SY5Y neuroblastoma cells from
MPP
+
-induced cytotoxicity. Treatment of SH-SY5Y cells with CBR-470-1, an inhibitor of the glycolytic enzyme
phosphoglycerate kinase 1
(
PGK1
), leads to methylglyoxal modification of Keap1, Keap1-Nrf2 disassociation, and increased expression of Nrf2 responsive genes. Pretreatment with CBR-470-1 potently attenuated
MPP
+
-induced oxidative injury and SH-SY5Y cell apoptosis. CBR-470-1 neuroprotection is dependent upon Nrf2, as Nrf2 shRNA or CRISPR/Cas9-mediated Nrf2 knockout, abolished CBR-470-1-induced SH-SY5Y cytoprotection against
MPP
+
. Consistent with these findings,
PGK1
depletion or knockout mimicked CBR-470-1-induced actions and rendered SH-SY5Y cells resistant to
MPP
+
-induced cytotoxicity. Furthermore, activation of the Nrf2 cascade by CRISPR/Cas9-induced Keap1 knockout protected SH-SY5Y cells from
MPP
+
. In Keap1 or
PGK1
knockout SH-SY5Y cells,CBR-470-1 failed to offer further cytoprotection against
MPP
+
. Collectively
PGK1
inhibition by CBR-470-1 protects SH-SY5Y cells from
MPP
+
via activation of the Keap1-Nrf2 cascade.
...
PMID:PGK1 inhibitor CBR-470-1 protects neuronal cells from MPP+. 3264 11
