Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vulnerability of pre-myelinating oligodendrocytes (PreOLs) to ischemic injury plays an important role in the pathogenesis and progression of perinatal white matter injury. Although oxidative stress is thought to be a major pathogenic mechanism predisposing the PreOLs to injury, no effective therapies have been identified to date. The present study aimed to investigate the direct protective effects of catalpol, a potent antioxidant and free radical scavenger, on ischemia-induced oxidative damage in PreOLs and to explore whether the ERK1/2 signaling pathway contributed to the protection provided by catalpol. Primary cultures of PreOLs exposed to oxygen-glucose deprivation (OGD) followed by reperfusion were used as an in vitro model of ischemia. Pretreatment with 0.5 mM catalpol for 1 h prior to OGD treatment significantly reversed ischemia-induced apoptosis in PreOLs and myelination deficits by inhibiting intracellular Ca2+ increase, reducing mitochondrial damage, and ameliorating overproduction of reactive oxygen species (ROS). The expression levels of phosphorylated ERK1/2 (p-ERK1/2) and activated poly-ADP-ribose polymerase-1 (PARP-1) were also markedly decreased by catalpol treatment. Blocking the ERK1/2 signaling pathway with the MEK inhibitor U0126 and catalpol significantly protected PreOLs from ROS-mediated apoptosis under OGD. Taken together, these results suggest that catalpol protects PreOLs against ischemia-induced oxidative injury through ERK1/2 signaling pathway. Catalpol may be a candidate for treating ischemic white matter damage.
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PMID:Catalpol Protects Pre-Myelinating Oligodendrocytes against Ischemia-induced Oxidative Injury through ERK1/2 Signaling Pathway. 2799 7

The degeneration of dopaminergic (DA) neurons in Parkinson's disease (PD) is related to inflammation and oxidative stress. Anti-inflammatory agents could reduce the risk or slow the progression of PD. Catalpol, an iridoid glycoside extracted from the roots of Rehmannia radix, has been reported to reduce the release of inflammatory factors and exert neuroprotective effects. 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP)-treated mice were used as the PD model and the roles of catalpol on DA neurons and its potential mechanism were investigated in this study. We found that catalpol administration mitigated the loss of DA neurons induced by MPTP and increased exploratory behavior along with tyrosine hydroxylase (TH) expression, which was accompanied by astrocyte and microglia activation. Importantly, catalpol administration significantly inhibited MPTP-triggered oxidative stress, restored growth-associated protein 43 (GAP43) and vascular endothelial growth factor (VEGF) levels. Further, we found that catalpol suppressed the activation of MKK4/JNK/c-Jun signaling, and reduced the pro-inflammatory factors and inflammasome in the mouse model of PD. Our results suggest that catalpol relieves MPTP-triggered oxidative stress, which may benefit to avoid the occurrence of chronic inflammatory reaction. Catalpol alleviates MPTP-triggered oxidative stress and thereby prevents neurodegenerative diseases-related inflammatory reaction, highlighting its therapeutic potential for the management of PD symptoms.
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PMID:Catalpol Exerts a Neuroprotective Effect in the MPTP Mouse Model of Parkinson's Disease. 3184 36