Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple factors are known to contribute to the pathogenesis of cerebral ischemic injury, including microRNAs (miRNAs). However, the precise mechanism of miRNAs involvement in cerebral ischemia remains largely unclear. In the current study, we found that miR-217 was significantly upregulated in ischemic stroke models, and the upregulation of miR-217 was associated with the development of post-stroke cognitive impairment. Further investigation revealed that myocyte enhancer factor 2D (MEF2D) was the direct target of miR-217. In vitro experiments showed that miR-217 promoted aggregation of histone deacetylase 5 (HDAC5) in cell nuclei by targeting MEF2D, which led to decreased expression of interleukin (IL)-10. In addition, miR-217 inhibited the expression of NADH dehydrogenase subunit 6 (ND6) in a MEF2D-dependent manner. Overexpression of MEF2D can reverse oxygen-glucose deprivation (OGD)-induced downregulation of ND6 and OGD-mediated neuronal apoptosis, and also reduce the elevated generation of reactive oxygen species (ROS) induced by OGD. Additionally, we found that in vivo administration of MEF2D overexpression plasmids increased IL-10 production and ameliorated cognitive impairment after cerebral ischemia. Taken together, these findings reveal a novel pathogenetic mechganism of cerebral ischemia-related brain injury involving the miR-217/MEF2D/HDAC5 axis and the miR-217/MEF2D/ND6 axis.
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PMID:miR-217-regulated MEF2D-HDAC5/ND6 signaling pathway participates in the oxidative stress and inflammatory response after cerebral ischemia. 3231 45

Accumulating evidence suggests that myocyte enhancer factor 2D (MEF2D) is a pro-survival factor for neurons. However, whether MEF2D is involved in protecting neurons from cerebral ischemia/reperfusion injury remains unknown. The current study was designed to investigate the exact role and mechanism of MEF2D in regulating oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced neuronal injury, an in vitro model used to study cerebral ischemia/reperfusion injury. MEF2D expression was significantly induced in neurons in response to OGD/R injury. Functional analysis demonstrated that MEF2D upregulation significantly rescued the decreased viability of OGD/R-injured neurons and suppressed OGD/R-induced apoptosis and reactive oxygen species (ROS) production. By contrast, MEF2D knockdown increased the sensitivity of neurons to OGD/R-induced injury. Moreover, MEF2D overexpression increased the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and enhanced the activation of Nrf2 antioxidant signaling. However, Nrf2 knockdown partially blocked the MEF2D-mediated neuroprotective effect in OGD/R-exposed neurons. Overall, these results reveal that MEF2D overexpression attenuates OGD/R-induced injury by enhancing Nrf2-mediated antioxidant signaling. These findings suggest that MEF2D may serve as a neuroprotective target with a potential application for treatment of cerebral ischemia/reperfusion injury.
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PMID:MEF2D upregulation protects neurons from oxygen-glucose deprivation/re-oxygenation-induced injury by enhancing Nrf2 activation. 3240 13