REDD1 Mediates Liver Ischemia-Reperfusion Injury Through NF-kB in A TLR4-Dependant Manner

Eid, Raymond E.; Evankovich, John; Zhang, R.; Nace, Gary W.; Huang, Hai; Tsung, Allan

doi:10.1016/j.jss.2011.11.401

Cited by 1 publication

(4 citation statements)

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“…Similarly, a former study confirmed the high expression of REDD1 in a liver I/R model, and its knockdown was protective against liver I/R injury in mice. 11 Analogously, REDD1 silencing alleviated methamphetamine-triggered cardiomyocyte and dopaminergic neuron death. 10,17 The occurrence of oxidative stress after ischemic reperfusion is a major culprit in exacerbating the progression of I/R injury.…”

Section: Discussionmentioning

confidence: 99%

“…These results indicate that REDD1 inhibition may protect against simulated I/R injury in neurons. Similarly, a former study confirmed the high expression of REDD1 in a liver I/R model, and its knockdown was protective against liver I/R injury in mice . Analogously, REDD1 silencing alleviated methamphetamine‐triggered cardiomyocyte and dopaminergic neuron death …”

Section: Discussionmentioning

confidence: 99%

“…10 Moreover, REDD1 −/− mice exhibited obvious protection against hepatic injury after liver I/R. 11 Nevertheless, the function and mechanism of REDD1 in cerebral ischemic stroke are poorly elucidated. In the present study, we investigated the expression and roles of REDD1 in neurons under simulated I/R injury in vitro by exposure to oxygen glucose deprivation/reoxygenation (OGD/R).…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, knockdown of REDD1 reduced autophagy and apoptosis in methamphetamine‐triggered dopaminergic neurons . Moreover, REDD1 −/− mice exhibited obvious protection against hepatic injury after liver I/R . Nevertheless, the function and mechanism of REDD1 in cerebral ischemic stroke are poorly elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Suppression of REDD1 attenuates oxygen glucose deprivation/reoxygenation‐evoked ischemic injury in neuron by suppressing mTOR‐mediated excessive autophagy

Sun

Yue

2019

J of Cellular Biochemistry

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Cerebral ischemia/reperfusion (I/R) typically occurs after mechanical thrombectomy to treat ischemic stroke, generation of reactive oxygen species (ROS) after reperfusion may result in neuronal insult, ultimately leading to disability and death. Regulated in development and DNA damage responses 1 (REDD1) is a conserved stress response protein under various pathogenic conditions. Recent research confirms the controversial role of REDD1 in injury processes. Nevertheless, the role of REDD1 in cerebral I/R remains poorly defined. In the current study, increased expression of REDD1 was observed in neurons exposed to simulated I/R via oxygen glucose deprivation/reoxygenation (OGD/R) treatment. Knockdown of REDD1 enhanced OGD/R‐inhibited cell viability, but suppressed lactate dehydrogenase (LDH) release in neurons upon OGD/R. Simultaneously, suppression of REDD1 also antagonized OGD/R‐evoked cell apoptosis, Bax expression, and caspase‐3 activity. Intriguingly, REDD1 depression abrogated neuronal oxidative stress under OGD/R condition by suppressing ROS, MDA generation, and increasing antioxidant SOD levels. Further mechanism analysis corroborated the excessive activation of autophagy in neurons upon OGD/R with increased expression of autophagy‐related LC3 and Beclin‐1, but decreased autophagy substrate p62 expression. Notably, REDD1 inhibition reversed OGD/R‐triggered excessive neuronal autophagy. More importantly, depression of REDD1 also elevated the expression of p‐mTOR. Preconditioning with mTOR inhibitor rapamycin engendered not only a reduction in mTOR activation, but also a reactivation of autophagy in REDD1 knockdown‐neurons upon OGD/R. In addition, blocking the mTOR pathway muted the protective roles of REDD1 inhibition against OGD/R‐induced neuron injury and oxidative stress. Together these data suggested that REDD1 may regulate I/R‐induced oxidative stress injury in neurons by mediating mTOR‐autophagy signaling, supporting a promising therapeutic strategy against brain ischemic diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%