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)

Senescence marker protein 30 (SMP30) is a senescence marker molecule and identified as a calcium regulatory protein. Currently, SMP30 has emerged as a cytoprotective protein in a wide range of cell types. However, the role of SMP30 in regulating neuronal survival during cerebral ischemia/reperfusion injury remains unclear. In the present study, we aimed to investigate the biological function and regulatory mechanism of SMP30 on neuronal survival using a cellular model induced by oxygen-glucose deprivation/reoxygenation (OGD/R). The results showed that SMP30 expression was significantly decreased by OGD/R exposure in neurons. Functional experiments demonstrated that SMP30 overexpression significantly rescued the decreased cell viability and attenuated the apoptosis and reactive oxygen species generation in OGD/R-exposed neurons. By contrast, SMP30 knockdown exhibited the opposite effect. Mechanism research revealed that SMP30 overexpression contributed to the activation of nuclear factor erythroid 2-related factor (Nrf2)/antioxidant response element (ARE) signaling associated with downregulation of Kelch-like ECH-associated protein (Keap1). Keap1 overexpression or Nrf2 silencing significantly reversed SMP30-mediated neuroprotection against OGD/R-induced injury. Overall, these findings demonstrate that SMP30 overexpression protects neurons from OGD/R-induced apoptosis and oxidative stress by enhancing Nrf2/ARE antioxidant signaling via inhibition of Keap1. These data highlight the importance of the SMP30/Keap1/Nrf2/ARE signaling axis in regulating neuronal survival during cerebral ischemia/reperfusion injury.
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PMID:Senescence marker protein 30 confers neuroprotection in oxygen-glucose deprivation/reoxygenation-injured neurons through modulation of Keap1/Nrf2 signaling: Role of SMP30 in OGD/R-induced neuronal injury. 3290 58

Sestrin1 (Sesn1) acts as a stress-inducible protein that performs a remarkable cytoprotective function upon diverse cellular stresses. However, whether Sesn1 exerts a cytoprotective role in neurons following cerebral ischemia/reperfusion injury is unknown. The goal of this work was to evaluate the role of Sesn1 in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal injury in vitro. The induction of Sesn1 was found in neurons exposed to OGD/R treatment. The silencing of Sesn1 rendered neurons more vulnerable to OGD/R injury, while the up-regulation of Sesn1 ameliorated OGD/R-induced neuronal injury by reducing apoptosis and the generation of reactive oxygen species (ROS). Furthermore, the up-regulation of Sesn1 promoted the activity of the nuclear factor-erythroid 2-related factor 2 (Nrf2) by down-regulating the expression of the Kelchlike ECH-associated protein 1 (Keap1). The restoration of Keap1 or the suppression of Nrf2 remarkably abolished the Sesn1-induced neuroprotection effects in OGD/R-exposed neurons. In summary, our work indicates that Sesn1 is a remarkable neuroprotective protein that potentiates Nrf2 activation via Keap1 to ameliorate OGD/R-induced injury.
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PMID:Sestrin1 exerts a cytoprotective role against oxygen-glucose deprivation/reoxygenation-induced neuronal injury by potentiating Nrf2 activation via the modulation of Keap1. 3306 34