AMPK/mTOR Signaling in Autophagy Regulation During Cisplatin-Induced Acute Kidney Injury

Wang, Ying; Liu, Zhiwen; Shu, Shaoqun; Cai, Juan; Tang, Chengyuan; Dong, Zheng

doi:10.3389/fphys.2020.619730

Cited by 80 publications

(45 citation statements)

References 79 publications

(108 reference statements)

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“…The AMPK/mTOR pathway was shown to modulate autophagy in liver, renal, and heart disease [ 34 – 36 ]. AMPK is essential for autophagy initiation under cellular stress, including glucose starvation and ROS-related oxidative stress [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Betulinic acid induces autophagy-dependent apoptosis via Bmi-1/ROS/AMPK-mTOR-ULK1 axis in human bladder cancer cells

Zhang

Zhou

et al. 2021

Aging

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Betulinic acid (BA), a pentacyclic triterpenoid isolated from tree bark, exhibits antitumor effects against solid malignancies and triggers autophagy and/or apoptosis in human cancer cells. Nonetheless, the relationship between autophagy and apoptosis and the potential modulatory actions of BA on autophagy-dependent bladder cancer cell death remain unclear. The present study showed that BA exposure significantly suppressed viability, proliferation, and migration of EJ and T24 human bladder cancer cells. These effects reflected caspase 3-mediated apoptosis and could be attenuated or abolished by inhibiting ROS production with N-acetyl-L-cysteine, inhibiting autophagy with chloroquine, or silencing ATG7 with targeted siRNA. BA-induced autophagy was evidenced by epifluorescence imaging of lentivirus-induced expression of mCherry-GFP-LC3B and increased expression of two autophagy-related proteins, LC3B-II and TEM. Moreover, enhanced AMPK phosphorylation and decreased mTOR and ULK-1 phosphorylation suggested BA activates autophagy via the AMPK/mTOR/ULK1 pathway. Accordingly, exposure to dorsomorphin (Compound C), an AMPK inhibitor, and AICAR, an AMPK activator, respectively inhibited and stimulated BA-induced autophagy in EJ and T24 cells. The effects of Bmi-1 overexpression in vitro and decreased Bmi-1 expression in BA-treated T24 cell xenografts in nude mice suggested that downregulation of Bmi-1 is the underlying mechanism in BA-mediated, autophagy-dependent apoptosis.

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Section: Discussionmentioning

confidence: 99%

Betulinic acid induces autophagy-dependent apoptosis via Bmi-1/ROS/AMPK-mTOR-ULK1 axis in human bladder cancer cells

Zhang

Zhou

et al. 2021

Aging

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“…Additionally, a KEGG analysis further revealed differential genes mainly involved in the regulation of the AMPK signaling pathway after the knockdown of WTAP in HCC (Figure 2D). At present, the AMPK signaling pathway is reported to participate in the regulation of cellular autophagy [24,25]. Therefore, the knockdown of WTAP could facilitate the AMPK signaling pathway of HCC, which may be responsible for the regulation of intracellular autophagy.…”

Section: Autophagy Facilitated By Upregulated Phosphorylation Of Ampkmentioning

confidence: 94%

m6A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK

Deng

Huang

et al. 2021

Genes

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The N6-methyladenosine (m6A) RNA modification can regulate autophagy to modulate the growth and development of tumors, but the mechanism of m6A modification for the regulation of autophagy in hepatocellular carcinoma cells (HCC) remains unclear. In the study, the knockdown of the Wilms’ tumor 1-associating protein (WTAP) was made in HCC to study the correlation between m6A modification and autophagy. A fluorescent confocal microscopy analysis showed that the knockdown of WTAP could facilitate the autophagy of HCC. A Western blot analysis showed that the level of p-AMPK was decreased in WTAP-knockdown HCC cells. Additionally, LKB1, the upstream kinase of AMPK, was regulated by WTAP and it could mediate the phosphorylation of AMPK in an m6A-dependent manner. Further studies revealed that the knockdown of WTAP could reduce the level of LKB1 mRNA with m6A. This could result in the increased stability of LKB1 mRNA to promote its expression. The knockdown of WTAP could upregulate the level of autophagy and inhibit HCC proliferation. However, the overexpression of WTAP could resist autophagic cell death.

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“…ON promotes autophagy via the AMPK/mTOR pathway. The AMPK/mTOR signaling pathway serves an important role in autophagy (18). Therefore, it was hypothesized that ON may also engage autophagy through this pathway.…”

Section: Ononin Suppresses H 2 O 2 -Induced H9c2 Cardiomyocyte Apoptosis By Enhancing Autophagymentioning

confidence: 99%

Ononin alleviates H₂O₂‑induced cardiomyocyte apoptosis and improves cardiac function by activating the AMPK/mTOR/autophagy pathway

2021

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Ononin (ON) is an isoflavone with numerous reported bioactivities, including anti-oxidative, anti-inflammatory and neuroprotective effects. Autophagy is a critical homeostatic process in the body that has been reported to closely associate with the apoptotic processes of cardiomyocytes. Using flow cytometry, western blotting, echocardiography and Masson's staining, the present study investigated the effects of ON on H 2 O 2 -induced cardiomyocyte apoptosis and myocardial infarction, in addition to any potential underlying molecular mechanisms. H 2 O 2 treatment reliably induced apoptosis in H9C2 cells. The anti-apoptotic effects of ON were revealed by flow cytometry results and by the downregulation of cleaved-caspase 3. Further investigations indicated that ON may alleviate apoptosis by enhancing autophagy, as evidenced by increased microtubule-associated proteins 1A/1B light chain 3B expression and p62 degradation. Activation of the 5' AMP-activated protein kinase (AMPK)/mTOR pathway was observed after ON administration following H 2 O 2 -induced cardiomyocyte injury. However, these anti-apoptotic effects mediated by ON were lost after autophagy inhibition by chloroquine or AMPK inhibition by Compound C. Finally, the protective effects of ON on cardiomyocytes in vitro could also be observed in vivo . A myocardial infarction model was established by ligating the left anterior descending branch of the rat heart. Using echocardiography and Masson's staining, ON was shown to increase the ejection fraction and decrease cardiac fibrosis in rats with myocardial infarction. These results suggest that ON exerts cardioprotective effects by improving autophagy via the AMPK/mTOR signaling pathway.

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AMPK/mTOR Signaling in Autophagy Regulation During Cisplatin-Induced Acute Kidney Injury

Cited by 80 publications

References 79 publications

Betulinic acid induces autophagy-dependent apoptosis via Bmi-1/ROS/AMPK-mTOR-ULK1 axis in human bladder cancer cells

Betulinic acid induces autophagy-dependent apoptosis via Bmi-1/ROS/AMPK-mTOR-ULK1 axis in human bladder cancer cells

m6A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK

Ononin alleviates H₂O₂‑induced cardiomyocyte apoptosis and improves cardiac function by activating the AMPK/mTOR/autophagy pathway

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AMPK/mTOR Signaling in Autophagy Regulation During Cisplatin-Induced Acute Kidney Injury

Cited by 80 publications

References 79 publications

Betulinic acid induces autophagy-dependent apoptosis via Bmi-1/ROS/AMPK-mTOR-ULK1 axis in human bladder cancer cells

Betulinic acid induces autophagy-dependent apoptosis via Bmi-1/ROS/AMPK-mTOR-ULK1 axis in human bladder cancer cells

m6A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK

Ononin alleviates H2O2‑induced cardiomyocyte apoptosis and improves cardiac function by activating the AMPK/mTOR/autophagy pathway

Contact Info

Product

Resources

About

Ononin alleviates H₂O₂‑induced cardiomyocyte apoptosis and improves cardiac function by activating the AMPK/mTOR/autophagy pathway