Angiotensin II induces calcium-mediated autophagy in podocytes through enhancing reactive oxygen species levels

Gao, Na; Wang, Hui; Yin, Hongqiang; Yang, Zhuo

doi:10.1016/j.cbi.2017.09.010

Cited by 21 publications

(17 citation statements)

References 65 publications

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“…In 2015, Yu et al 55 reported that Ang II activates autophagy in podocyte and that silencing TRPC6 could stabilize autophagy induced by Ang II. Recently, Gao et al 56 demonstrated that Ang II could increase TRPC6-mediated Ca 2+ influx and enhance autophagy in podocytes. These data, in contrast to ours, showed an activating effect of TRPC6 on autophagy in podocytes.…”

Section: Discussionmentioning

confidence: 99%

Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation

et al. 2018

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Reactive oxygen species (ROS) are generated under various pathological conditions such as renal ischemia/reperfusion (I/R) injury and provoke damage to multiple cellular organelles and processes. Overproduction of ROS causes oxidative stress and contributes to damages of renal proximal tubular cells (PTC), which are the main cause of the pathogenesis of renal I/R injury. Autophagy is a dynamic process that removes long-lived proteins and damaged organelles via lysosome-mediated degradation, which has an antioxidant effect that relieves oxidative stress. The canonical transient receptor potential channel 6 (TRPC6), a nonselective cation channel that allows passage of Ca2+, plays an important role in renal disease. Yet, the relationship between TRPC6 and autophagy, as well as their functions in renal oxidative stress injury, remains unclear. In this study, we found that oxidative stress triggered TRPC6-dependent Ca2+ influx in PTC to inhibit autophagy, thereby rendering cells more susceptible to death. We also demonstrated that TRPC6 knockout (TRPC6-/-) or inhibition by SAR7334, a TRPC6-selective inhibitor, increased autophagic flux and mitigated oxidative stress-induced apoptosis of PTC. The protective effects of TRPC6 ablation were prevented by autophagy inhibitors Chloroquine and Bafilomycin A1. Moreover, this study also shows that TRPC6 blockage promotes autophagic flux via inhibiting the PI3K/Akt/mTOR and ERK1/2 signaling pathways. This is the first evidence showing that TRPC6-mediated Ca2+ influx plays a novel role in suppressing cytoprotective autophagy triggered by oxidative stress in PTC, and it may become a novel therapeutic target for the treatment of renal oxidative stress injury in the future.

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Section: Discussionmentioning

confidence: 99%

Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation

et al. 2018

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“…Recent studies have shown that Ang II can activate and/or trigger various cellular events (e.g. oxidative stress and reactive oxygen species overproduction, endoplasmic reticulum stress, autophagy and mitochondrial dysfunction), thus resulting in cytoskeletal rearrangement and podocyte apoptosis [4][5][6][7][8][9]. Notably, NADPH oxidase (Nox) plays a critical role in driving reactive oxygen species (ROS) production.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway

Che

Gao

et al. 2020

PLoS ONE

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Angiotensin II (Ang II) is a key contributor to glomerular disease by predominantly resulting in podocyte injury, whereas the underlying molecular mechanisms has not been fully understood. This study aimed to investigate if and how ADP-ribosylation factor 6 (Arf6), a small GTP-binding protein, involves Ang II-induced cellular injury in cultured human podocytes. Cellular injury was evaluated with caspase 3 activity, reactive oxygen species (ROS) level and TUNEL assay. Arf6 activity was measured using an Arf6-GTP Pull-Down Assay. Ang II significantly enhanced Arf6 expressions accompanied by increase of Arf6-GTP. The TUNEL-positive cells as well as activated caspase 3, NADPH oxidase 4 protein (Nox4) and ROS levels were dramatically increased in Ang II-treated podocytes, which was prevented by secinH3, an Arf6 activity inhibitor. Induction of ROS by Ang II was inhibited in podocytes with Nox4 knockdown. Ang II-induced elevation of Nox4 and ROS was prevented by Arf6 knockdown. Phpspho-Erk1/2 Thr202/Tyr204 levels were upregulated remarkably following Ang II treatment, and Erk inhibitor LY3214996 significantly downregulated Nox4 expression. In addition, Ang II decreased CD2AP expression. Overexpression of CD2AP prevented Ang IIinduced upregulation of Arf6-GTP. Our data demonstrated that Ang II promotes ROS production and podocytes injury through activation of Arf6-Erk1/2-Nox4 signaling. We also provided evidence that Ang II activates Arf6 by degradation of CD2AP.

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“…Lung cancer, which is one of the leading causes of cancer death around the world [ 1 ], shows an increasing level of reactive oxygen species (ROS) than normal cells [ 2 , 3 ]. However, with the increasing level of ROS, cells will be subject to irreversible oxidative damage [ 4 , 5 ]. Therefore, more and more studies on the destruction of the maintenance of redox balance have been raised [ 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

T59, a New Compound Reconstructed from Curcumin, Induces Cell Apoptosis through Reactive Oxygen Species Activation in Human Lung Cancer Cells

et al. 2018

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Curcumin is acknowledged for its antioxidant, anti-inflammatory, anti-cancer, and wound-healing properties. However, the biological activity and the molecular mechanisms of T59, which is a new derivative of curcumin, are not fully understood. The present study was aimed to determine the cytoxicity role of T59 in human lung cancer and the molecular mechanisms. Cytotoxicity and cell apoptosis effects induced by T59 were determined by MTT, AO staining, Annexin V, and JC-1. Compared with curcumin, T59 exerted more effective cytotoxicity and cell apoptosis effects in A549 and H1975. With the decreasing level of the mitochondrion membrane potential, the generation of reactive oxygen species (ROS) was increased and induced by T59. Furthermore, the expressions of cleaved-caspase-3 and Bax were increased, which were reversed by NAC mainly through the PI3K/AKT signaling pathway. Our results suggested that T59 has the potential for further investigation and study to act as an anti-cancer therapeutic against human lung cancer.

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Angiotensin II induces calcium-mediated autophagy in podocytes through enhancing reactive oxygen species levels

Cited by 21 publications

References 65 publications

Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation

Transient receptor potential channel 6 knockdown prevents apoptosis of renal tubular epithelial cells upon oxidative stress via autophagy activation

Angiotensin II promotes podocyte injury by activating Arf6-Erk1/2-Nox4 signaling pathway

T59, a New Compound Reconstructed from Curcumin, Induces Cell Apoptosis through Reactive Oxygen Species Activation in Human Lung Cancer Cells

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