Rapamycin attenuates mitochondrial injury and renal tubular cell apoptosis in experimental contrast-induced acute kidney injury in rats

Yang, Xueyan; Yan, Xiao‐Jie; Yang, Dingping; Zhou, Junke; Song, Jie; Yang, Dingwei

doi:10.1042/bsr20180876

Cited by 49 publications

(38 citation statements)

References 32 publications

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“…Rapamycin treatment, as a positive control, also induced a large number of autophagic fluorescent spots. The red fluorescent expression of cells in the positive control group was stronger than that in the GOtreated group, which showed that rapamycin enhanced autophagy [37]. The fluorescence microscopy results further confirmed that GO triggered autophagy in F98 cells, which was consistent with the TEM results.…”

Section: Autophagy Is Triggered Following Go Exposuresupporting

confidence: 83%

The interrupted effect of autophagic flux and lysosomal function induced by graphene oxide in p62-dependent apoptosis of F98 cells

Zhang

Feng

et al. 2020

J Nanobiotechnol

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Background: Graphene oxide (GO) nanoparticles (NPs) have been widely applied in various fields, especially in biomedical applications. Extensive studies have suggested that GO can pass through the blood-brain barrier (BBB) and induce abnormal autophagy and cytotoxicity in the central nervous system (CNS). However, the effect and specific mechanism of GO on astrocytes, the most abundant cells in the brain still has not been extensively investigated. Results: In this study, we systematically explored the toxicity and mechanism of GO exposure in the rat astrogliomaderived F98 cell line using molecular biological techniques (immunofluorescence staining, flow cytometry and Western blot) at the subcellular level and the signaling pathway level. Cells exposed to GO exhibited decreased cell viability and increased lactate dehydrogenase (LDH) release in a concentration-and time-dependent manner. GO-induced autophagy was evidenced by transmission electron microscopy (TEM) and immunofluorescence staining. Western blots showed that LC3II/I and p62 were upregulated and PI3K/Akt/mTOR was downregulated. Detection of lysosomal acidity and cathepsin B activity assay indicated the impairment of lysosomal function. Annexin V-FITC-PI detection showed the occurrence of apoptosis after GO exposure. The decrease in mitochondrial membrane potential (MMP) with an accompanying upregulation of cleaved caspase-3 and Bax/Bcl-2 further suggested that endogenous signaling pathways were involved in GO-induced apoptosis. Conclusion: The exposure of F98 cells to GO can elicit concentration-and time-dependent toxicological effects. Additionally, increased autophagic response can be triggered after GO treatment and that the blocking of autophagy flux plays a vital role in GO cytotoxicity, which was determined to be related to dysfunction of lysosomal degradation. Importantly, the abnormal accumulation of autophagic substrate p62 protein can induce capase-3-mediated apoptosis. Inhibition of abnormal accumulation of autophagic cargo could alleviate the occurrence of GO-induced apoptosis in F98 cells.

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Section: Autophagy Is Triggered Following Go Exposuresupporting

confidence: 83%

The interrupted effect of autophagic flux and lysosomal function induced by graphene oxide in p62-dependent apoptosis of F98 cells

Zhang

Feng

et al. 2020

J Nanobiotechnol

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“…Mitophagy plays an important role in the clearance of damaged mitochondria (Linkermann et al, 2014). The reduction of mitophagy significantly exacerbated cell apoptosis and tissue damage of AKI (Zhao et al, 2017;Tang et al, 2018;Yang et al, 2018). In the present study, activation of mitophagy was found in HK-2 cells after I/R treatment.…”

Section: Discussionsupporting

confidence: 55%

Augmenter of Liver Regeneration Protects Renal Tubular Epithelial Cells From Ischemia-Reperfusion Injury by Promoting PINK1/Parkin-Mediated Mitophagy

et al. 2020

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Ischemia-reperfusion (I/R) is the most common cause of acute kidney injury (AKI) and can induce apoptosis in renal epithelial tubule cells. Mitochondrial dysfunction is one of the main reasons for I/R-induced apoptosis. Accumulating evidence suggests that PINK1/Parkin-mediated mitophagy possibly plays a renoprotective role in kidney disease by removing impaired mitochondria and preserving a healthy population of mitochondria. Our previous study showed that augmenter of liver regeneration (ALR) alleviates tubular epithelial cells apoptosis in rats with AKI, although the specific mechanism remains unclear. In this study, we investigated the role of ALR in I/Rinduced mitochondrial pathway of apoptosis. We knocked down ALR with short hairpin RNA lentiviral and established an I/R model in human kidney proximal tubular (HK-2) cells in vitro. We observed that the knockdown of ALR aggravated mitochondrial dysfunction and increased the mitochondrial reactive oxygen species (ROS) levels, leading to an increase in cell apoptosis via inhibition of mitophagy. We also found that the PINK1/Parkin pathway was activated by I/R via confocal microscopy and Western blot. Furthermore, the knockdown of ALR suppressed the activation of PINK1 and Parkin. These findings collectively indicate that ALR may protect HK-2 cells from I/R injury by promoting mitophagy, and the mechanism by which ALR regulates mitophagy seems to be related to PINK1 and Parkin. Consequently, ALR may be used as a potential therapeutic agent for AKI in the future.

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“…Rapamycin treatment, as a positive control, also induced a large number of autophagic fluorescent spots. The red fluorescent expression of cells in the positive control group was stronger than that in the GO-treated group, which showed that rapamycin enhanced autophagy [37]. The fluorescence microscopy results further confirmed that GO triggered autophagy in F98 cells, which was consistent with the TEM results.…”

Section: Autophagy Is Triggered Following Go Exposuresupporting

confidence: 82%

The interrupted effect of autophagic flux and lysosomal function induced by graphene oxide in p62-dependent apoptosis of F98 cells

Zhang

Feng

et al. 2020

Preprint

View full text Add to dashboard Cite

Background : Graphene oxide (GO) nanoparticles (NPs) have been widely applied in various fields, especially in biomedical applications. Extensive studies have suggested that GO can pass through the blood-brain barrier (BBB) and induce abnormal autophagy and cytotoxicity in the central nervous system (CNS). However, the effect and specific mechanism of GO on astrocytes, the most abundant cells in the brain still has not been extensively investigated. Results: In this study, we systematically explored the toxicity and mechanism of GO exposure in the rat astroglioma-derived F98 cell line using molecular biological techniques (immunofluorescence staining, flow cytometry and Western blot) at the subcellular level and the signaling pathway level. Cells exposed to GO exhibited decreased cell viability and increased lactate dehydrogenase (LDH) release in a concentration- and time-dependent manner. GO-induced autophagy was evidenced by transmission electron microscopy (TEM) and immunofluorescence staining. Western blots showed that LC3II/I and p62 were upregulated and PI3K/Akt/mTOR was downregulated. Detection of lysosomal acidity and cathepsin B activity assay indicated the impairment of lysosomal function. Annexin V-FITC-PI detection showed the occurrence of apoptosis after GO exposure. The decrease in mitochondrial membrane potential (MMP) with an accompanying upregulation of cleaved caspase-3 and Bax/Bcl-2 further suggested that endogenous signaling pathways were involved in GO-induced apoptosis. Conclusion: The exposure of F98 cells to GO can elicit concentration- and time-dependent toxicological effects. Additionally, increased autophagic response can be triggered after GO treatment and that the blocking of autophagy flux plays a vital role in GO cytotoxicity, which was determined to be related to dysfunction of lysosomal degradation. Importantly, the abnormal accumulation of autophagic substrate p62 protein can induce capase-3-mediated apoptosis. Inhibition of abnormal accumulation of autophagic cargo could alleviate the occurrence of GO-induced apoptosis in F98 cells. Keyword: Graphene oxide; Astrocyte; p62; Autophagy; Apoptosis

show abstract

Rapamycin attenuates mitochondrial injury and renal tubular cell apoptosis in experimental contrast-induced acute kidney injury in rats

Cited by 49 publications

References 32 publications

The interrupted effect of autophagic flux and lysosomal function induced by graphene oxide in p62-dependent apoptosis of F98 cells

The interrupted effect of autophagic flux and lysosomal function induced by graphene oxide in p62-dependent apoptosis of F98 cells

Augmenter of Liver Regeneration Protects Renal Tubular Epithelial Cells From Ischemia-Reperfusion Injury by Promoting PINK1/Parkin-Mediated Mitophagy

The interrupted effect of autophagic flux and lysosomal function induced by graphene oxide in p62-dependent apoptosis of F98 cells

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