Propofol can suppress renal ischemia-reperfusion injury through the activation of PI3K/AKT/mTOR signal pathway

Wei, Quan; Zhao, Jinjuan; Zhou, Xingguo; Yu, Lili; Liu, Zhaohui; Chang, Yulin

doi:10.1016/j.gene.2019.05.023

Cited by 45 publications

(38 citation statements)

References 35 publications

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“…Wei et al 30 showed that propofol can protect renal ischemia-reperfusion injury by reducing apoptosis and inflammation partially via the modulation of the PI3K/ AKT/mTOR signaling pathway. Wang et al 17 demonstrated propofol postconditioning could provide neuroprotection against cerebral ischemic injury via PI3K/Akt pathway.…”

Section: Discussionmentioning

confidence: 99%

Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage: Involvement of PI3K/Akt Pathway

Zhang

Chen

et al. 2019

Journal of Stroke and Cerebrovascular Diseases

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Background: Our previous study showed that propofol, one of the widely used anesthetic agents, can attenuate subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) via inhibiting inflammatory and oxidative reaction. However, it is perplexing whether propofol attenuates inflammatory and oxidative reaction through modulating PI3K/Akt pathway. The present study investigated whether PI3K/Akt pathway is involved in propofol's anti-inflammation, antioxidation, and neuroprotection against SAH-induced EBI. Materials and methods: Adult Sprague-Dawley rats underwent SAH and received treatment with propofol or vehicle after 2 and 12 hours of SAH. LY294002 was injected intracerebroventricularly to selectively inhibit PI3K/Akt signaling. Mortality, SAH grading, neurological scores, brain water content, evans blue extravasation, myeloperoxidase, malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured 24 hours after SAH. Immunoreactivity of p-Akt, t-Akt, nuclear factor-kappa B (NF-kB) p65, nuclear factor erythroid-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase (NQO1), and cyclooxygenase-2 (COX-2) in rat brain was determined by western blot. Tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b) in rat brain were examined by ELISA. Results: Propofol significantly reduces neurological dysfunction, BBB permeability, brain edema, inflammation, and oxidative stress, all of which were reversed by LY294002. Propofol significantly upregulates the immunoreactivity of p-Akt, Nrf2, and NQO1, all of which were abolished by LY294002. Propofol significantly downregulates the overexpression of NF-kB p65, COX-2, TNF-a, and IL-1b, all of which were inhibited by LY294002. Conclusion: These results suggest that propofol attenuates SAH-induced EBI by inhibiting inflammatory reaction and oxidative stress, which might be associated with the activation of PI3K/Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage: Involvement of PI3K/Akt Pathway

Zhang

Chen

et al. 2019

Journal of Stroke and Cerebrovascular Diseases

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“…Numerous studies have demonstrated that PI3K/Akt/mTOR axis is involved in ischemic injury in various pathophysiological conditions [7,15,16]. mTOR has been reported to play a sig-nificant role in regulation of metabolism, gene transcription, protein synthesis and degradation, autophagy, apoptosis and necroptosis [17].…”

Section: Introductionmentioning

confidence: 99%

Endothelial protective effect of rapamycin against simulated ischemia injury through up-regulation of autophagy and inhibition of endoplasmic reticulum stress

Gabryel¹

2020

Arch Med Sci Civil Dis

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Introduction: Rapamycin has been shown to have cytoprotective properties in some experimental models of ischemia. However, the precise molecular mechanisms underlying the positive effect of rapamycin on endothelial cells in ischemic injury remain unknown. It is very important because endothelial cells are firstly exposed to ischemia and play an important role in ischemic organ damage. Autophagy and endoplasmic reticulum stress are suggested to be implicated in hypoxic/ischemic injury of endothelial cells. This study aims to explore whether the endothelial protective effect of rapamycin is associated with exacerbation of autophagy and attenuation of endoplasmic reticulum stress. Material and methods: The protective effects of rapamycin against oxygen and glucose deprivation (OGD)-induced cell injury were explored in human vascular endothelial cells (HUVECs). Cell viability was measured by MTT assay. The protein levels of Beclin 1, p62, p-mTOR, p-S6K, p-4EBP, GRP78, p-PERK and p-IRE1 were analyzed using immunoblotting. Results: Rapamycin in the simulated ischemia model increased the cell viability, indicating its cytoprotective effect (p < 0.05). Experiments with 3-methyladenine as an inhibitor of autophagy and thapsigargin as an inducer of endoplasmic reticulum stress support that rapamycin exerts endothelial protective effects against OGD-induced damage via autophagy-endoplasmic reticulum stress pathway. Conclusions: This study demonstrated that rapamycin protects ischemic HUVECs via down-regulation of the mTOR pathway, enhancement of autophagy and inhibition of endoplasmic reticulum stress.

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“…In a recent study, Saha et al, revealed that mangiferin ameliorates kidney injury, induced by an oxidative stress inducer, tBHP, via the deactivation of stress kinases JNK and p38 and the activation of PI3K/Akt pathways [35]. In addition, by using the PI3K inhibitor LY294002, it was shown that propofol protects kidneys via the phosphorylation of PI3K/Akt pathway after kidney injury, which was associated with the improved serum BUN level [36]. Furthermore, it was shown that CP also activates Akt pathways via EGFRi, Src and PI3K, which was associated with the activation of p38 [37].…”

Section: Discussionmentioning

confidence: 98%

Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in Mice

et al. 2020

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Cisplatin (CP) is one of the most preferred platinum-containing antineoplastic drugs. However, even in nontoxic plasma concentrations, it may cause kidney injury. To be able to increase its effective pharmacological dose, its side effects need to be regarded. Diet restriction (DR) has been demonstrated to improve cellular survival in a number of disorders. In this context, we investigated the role of DR in CP-induced nephrotoxicity (CPN). Besides alternate DR, animals were exposed to DR for 3 days prior or after CP treatment. Here, we observed that both 3 days of DR reverses the nephrotoxic effect of CP, which was associated with improved physiological outcomes, such as serum creatine, blood-urea nitrogen and urea. These treatments significantly increased phosphorylation of survival kinases PI3K/Akt and ERK-1/2 and decreased the level of stress kinase JNK were noted. In addition, the activation level of signal transduction mediator p38 MAPK phosphorylation was higher particularly in both three-day DR groups. Next, animals were fed with carbohydrate-, protein- or fat-enriched diets in the presence of CP. Results indicated that not only fasting but also dietary content itself may play a determinant role in the severity of CPN. Our data suggest that DR is a promising approach to reduce CPN by regulating metabolism and cell signaling pathways.

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Propofol can suppress renal ischemia-reperfusion injury through the activation of PI3K/AKT/mTOR signal pathway

Cited by 45 publications

References 35 publications

Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage: Involvement of PI3K/Akt Pathway

Propofol Reduces Inflammatory Brain Injury after Subarachnoid Hemorrhage: Involvement of PI3K/Akt Pathway

Endothelial protective effect of rapamycin against simulated ischemia injury through up-regulation of autophagy and inhibition of endoplasmic reticulum stress

Short-Term Diet Restriction but Not Alternate Day Fasting Prevents Cisplatin-Induced Nephrotoxicity in Mice

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