Huang-Lian-Jie-Du-Decotion induced protective autophagy against the injury of cerebral ischemia/reperfusion via MAPK-mTOR signaling pathway

Wang, Pengran; Wang, Junsong; Zhang, Chao; Song, Xingfang; Tian, Na; Kong, Ling–Yi

doi:10.1016/j.jep.2013.06.035

Cited by 70 publications

(35 citation statements)

References 74 publications

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“…Therefore we hypothesize that AST may produce a marked effect through growth factors and downstream signaling pathways. The ERK, JNK and Akt signaling pathways may regulate neuronal survival and apoptosis following ischemia, but the majority of studies agree that the levels of p-ERK, p-JNK and p-Akt decrease after 24 h or more following ischemia (14,15), therefore the level of p-ERK, p-JNK and p-Akt was detected 22 h after reperfusion in the present study. The p-ERK levels were enhanced following use of a variety of protective agents, such as BDNF and erythropoietin (16)(17)(18).…”

Section: Discussionmentioning

confidence: 45%

Astragalosides attenuate learning and memory impairment in rats following ischemia-reperfusion injury

Gong

et al. 2014

Molecular Medicine Reports

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Abstract. Astragalosides (ASTs) have been traditionally used in the treatment of various cardiovascular and cerebrovascular diseases. The aim of the present study was to investigate the neuroprotective effects of AST on learning and memory following focal cerebral ischemia/reperfusion in a rat model. A Morris water maze was used to measure the effect of AST on learning and memory impairments. A histological examination and Hoechst 33258 staining was used to observe the neuronal changes and apoptosis in the hippocampus. The activity of phospho-extracellular signal-regulated kinases

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Section: Discussionmentioning

confidence: 45%

Astragalosides attenuate learning and memory impairment in rats following ischemia-reperfusion injury

Gong

et al. 2014

Molecular Medicine Reports

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“…In the present study, pretreatment with LA decreased the levels of MDA and NO in rat brains. The endogenous antioxidant enzymes, including SOD and glutathione (GSH) peroxidase and low-molecular weight ROS scavengers, including GSH, are critical in attenuating the injury induced by I/R (25,27). In the present study, LA enhanced the activities of T-AOC and SOD in rat brains.…”

Section: Discussionmentioning

confidence: 48%

“…The increased concentration of ROS can cause cellular damage and subsequent cell death since ROS may oxidize crucial cellular components, including lipids, proteins and DNA (24). The levels of MDA and NO increased indicating that severe oxidative damage was caused by I/R (25). It has been reported that LA has the capability to scavenge MDA and NO within brain tissue (26).…”

Section: Discussionmentioning

confidence: 99%

α-lipoic acid protects against cerebral ischemia/reperfusion-induced injury in rats

Deng

Zuo

Zhang

et al. 2015

Molecular Medicine Reports

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Abstract. It is well established that the brain is sensitive to ischemia/reperfusion (I/R)-induced injury. α-lipoic acid (LA), a free radical scavenger and antioxidant, has a neuroprotective effect against cerebral I/R-induced injury, however, the underlying mechanisms remain to be elucidated. Therefore, the present study was undertaken to evaluate whether LA was able to protect against cerebral I/R-induced injury and to examine the potential mechanisms. The neuroprotective effects of LA were investigated in a rat model of transient focal ischemia induced by middle cerebral artery occlusion (MCAO) followed by reperfusion. Adult male Sprague-Dawley rats were randomly assigned into the sham, cerebral I/R injury model and model plus LA groups. Cerebral I/R injury was induced by 90 min MCAO followed by reperfusion for 24 h. Cerebral infarct size was detected by 2,3,5-triphenyltetrazolium chloride staining. Neurological deficit score (NDS), brain water content and oxidative parameters, including malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) were measured. The expression of cleaved caspase-3, brain-derived neurotrophic factor (BDNF), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), p-Akt and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) were also analyzed using western blotting. The present study demonstrated that pretreatment with LA significantly decreased the infarction size, brain water content and improved NDS. LA reversed the levels of oxidative parameters, including MDA, NO, T-AOC and SOD to their normal state in rat brains following cerebral I/R. Furthermore, the expression of cleaved caspase-3 markedly decreased and the expression of BDNF, PI3K, p-Akt and p-ERK1/2 significantly increased following administration of LA. On the basis of these findings, it was concluded that LA protected the brain from cerebral I/R damage by attenuation of oxidative stress and caspase-dependent apoptosis. Furthermore, LA exerts its neuroprotective effects potentially through activation of the BDNF-PI3K/Akt-ERK1/2 pathway. IntroductionCerebral ischemic injury is one of the leading causes of human mortality and disability worldwide (1). Restoration of blood flow to the ischemic brain is often used to treat patients in clinical experiments. However, reperfusion itself also has the potential to produce additional injuries in the ischemic brain due to overproduction of reactive oxygen species (ROS). The potential pathological mechanisms of ischemia/reperfusion (I/R) injury include glutamate excitotoxicity, calcium overload, nitric oxide (NO) production, oxidative stress, inflammation and apoptosis, which eventually lead to cell death (2). Oxidative stress and apoptosis following cerebral I/R are the two major processes that induce neuronal injury (3,4). For this reason, multifunctional molecules with anti-oxidative and anti-apoptotic properties are ideal neuroprotective agents.α-lipoic acid (LA), an endogenous short-chain fatty acid, is a cofact...

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“…Grahammer et al [34] demonstrated that I/R injury exaggerated renal tubular damage in mTORC1-deficient mice. Evidence from other tissues or cell lines provided several signaling pathways that regulate autophagy during I/R or oxidative stress, including acetylated FOXO [33], AMPK/mTOR [35,36], and HO-1/p38-MAPK [37,38], but whether they involve in the renoprotection of autophagy during I/R needs to be further explored.…”

Section: Discussionmentioning

confidence: 99%

Autophagy Protects Renal Tubular Cells Against Ischemia / Reperfusion Injury in a Time-Dependent Manner

Guan

Qian

Shen

et al. 2015

Cell Physiol Biochem

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Background/Aims: Autophagy is a dynamic catabolic process that maintains cellular homeostasis. Whether it plays a role in promoting cell survival or cell death in the process of renal ischemia/reperfusion (I/R) remains controversial, partly because renal autophagy is usually examined at a certain time point. Therefore, monitoring of the whole time course of autophagy and apoptosis may help better understand the role of autophagy in renal I/R. Methods: Autophagy and apoptosis were detected after mice were subjected to bilateral renal ischemia followed by 0-h to 7-day reperfusion, exposure of TCMK-1 cells to 24-h hypoxia, and 2 to 24-h reoxygenation. The effect of autophagy on apoptosis was assessed in the presence of autophagy inhibitor 3-methyladenine (3-MA) and autophagy activator rapamycin. Results: Earlier than apoptosis, autophagy increased from 2-h reperfusion, reached the maximum at day 2, and then began declining from day 3 when renal damage had nearly recovered to normal. Exposure to 24-h hypoxia induced autophagy markedly, but it decreased drastically after 4 and 8-h reoxygenation, which was accompanied with increased cell apoptosis. Inhibition of autophagy with 3-MA increased the apoptosis of renal tubular cells during I/R in vivo and hypoxia/reoxygenation (H/R) in vitro. In contrast, activation of autophagy by rapamycin significantly alleviated renal tissue damage and tubular cell apoptosis in the two models. Conclusion: Autophagy was induced in a time-dependent manner and occurred earlier than the onset of cell apoptosis as an early response that played a renoprotective role during renal I/R and cell H/R. Up-regulation of autophagy may prove to be a potential strategy for the treatment of acute kidney injury.

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Huang-Lian-Jie-Du-Decotion induced protective autophagy against the injury of cerebral ischemia/reperfusion via MAPK-mTOR signaling pathway

Cited by 70 publications

References 74 publications

Astragalosides attenuate learning and memory impairment in rats following ischemia-reperfusion injury

Astragalosides attenuate learning and memory impairment in rats following ischemia-reperfusion injury

α-lipoic acid protects against cerebral ischemia/reperfusion-induced injury in rats

Autophagy Protects Renal Tubular Cells Against Ischemia / Reperfusion Injury in a Time-Dependent Manner

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