Stanniocalcin-1 Alleviates Contrast-Induced Acute Kidney Injury by Regulating Mitochondrial Quality Control via the Nrf2 Pathway

Zhao, Fei; Feng, Lixin; Liu, Qian; Wang, Hongshen; Tang, Chengyuan; Cheng, Wei; Deng, Yin-Hao; Wu, Xiaoxiang; Yan, Ping; Duan, Xiangjie; Peng, Jin-Cheng; Duan, Shao‐Bin

doi:10.1155/2020/1898213

Cited by 13 publications

(17 citation statements)

References 44 publications

(66 reference statements)

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“…Furthermore, the expressions of HO-1 and NQO1 were significantly upregulated, while the formation of the Keap1/Nrf2 protein complex was blocked ( Figure 8(e) ). It has been reported that ML385 is an inhibitor of Nrf2 [ 38 ]. In order to investigate if the protective effect of phillyrin occurred via activation of the Nrf2 signaling pathway, ML385 was added to the phillyrin intervention group.…”

Section: Resultsmentioning

confidence: 99%

Phillyrin Mitigates Apoptosis and Oxidative Stress in Hydrogen Peroxide-Treated RPE Cells through Activation of the Nrf2 Signaling Pathway

You

et al. 2020

Oxidative Medicine and Cellular Longevity

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Oxidative stress-induced dysfunction or apoptosis in retinal pigment epithelial (RPE) cells is an important cause of dry age-related macular degeneration (AMD). Although phillyrin has been shown to exert significant antioxidant effects, the underlying mechanism of action remains unclear. The purpose of this study was to investigate the protective effect of phillyrin on hydrogen peroxide- (H2O2-) induced oxidative stress damage in RPE cells and the potential mechanism involved. It was found that phillyrin significantly protected RPE cells from H2O2 cytotoxicity. Furthermore, phillyrin alleviated oxidative stress-induced apoptosis via inhibition of endogenous and exogenous apoptotic pathways. Compared with the H2O2-treated group, the expressions of cleaved caspase-3, cleaved caspase-9, cleaved polymerase (PARP), death receptor Fas, and cleaved caspase-8, as well as Bax/Bcl-2 ratio were decreased in RPE cells after the phillyrin intervention. In addition, phillyrin reversed the oxidative stress-induced reductions in superoxide dismutase (SOD) and glutathione (GSH) levels and annulled the elevations in reactive oxygen species (ROS) and malondialdehyde (MDA), thereby restoring oxidant-antioxidant homeostasis. Phillyrin treatment upregulated the expressions of cyclin E, cyclin-dependent kinase 2 (CDK2), and cyclin A and downregulated the expressions of p21 and p-p53, thereby reversing the G0/G1 cell cycle arrest in H2O2-treated RPE cells. Pretreatment with phillyrin also increased the expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), total Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductases-1 (NQO-1) in RPE cells and inhibited the formation of Kelch-like ECH-associated protein 1 (Keap1)/Nrf2 protein complex. Thus, phillyrin effectively protected RPE cells from oxidative stress through activation of the Nrf2 signaling pathway and inhibition of the mitochondria-dependent apoptosis pathway.

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Section: Resultsmentioning

confidence: 99%

Phillyrin Mitigates Apoptosis and Oxidative Stress in Hydrogen Peroxide-Treated RPE Cells through Activation of the Nrf2 Signaling Pathway

You

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…In particular, LC3-positive tubular epithelial cells were observed in the kidney with ioversol injection, whereas their numbers were reduced by paricalcitol pretreatment (Figures 4(c) and 4(d) ). To confirm the effect of paricalcitol on mitochondrial dysfunction caused by contrast, mitochondrial fusion proteins were examined; maintaining mitochondrial dynamics, including mitochondrial fusion and fission, is crucial for preserving mitochondrial function [ 29 ]. Levels of Mfn1 and Opa1, key regulators of mitochondrial fusion, were significantly increased only in the ioversol group, and pretreatment with paricalcitol attenuated their expression ( Figure 4(e) ).…”

Section: Resultsmentioning

confidence: 99%

“…In our study, mitochondrial ROS generation, damage, and mitophagy, which were increased by ioversol, were reversed by paricalcitol pretreatment. It was recently reported that stanniocalcin-1 (STC1) and tetramethylpyrazine (TMP) have protective effects on CI-AKI by regulating mitochondrial quality control and modulating tubular cell mitophagy, respectively [ 29 , 42 ]. Exogenous recombinant human STC1 administration reduced the expression of mfn2, TOMM20, and p62 induced by iohexol.…”

Section: Discussionmentioning

confidence: 99%

Paricalcitol Attenuates Contrast-Induced Acute Kidney Injury by Regulating Mitophagy and Senescence

Bae

Kim

Jung

et al. 2020

Oxidative Medicine and Cellular Longevity

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Contrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-acquired renal failure, with an incidence of 11%. However, the disease mechanism remains unclear, and no effective treatment is available. Paricalcitol has been reported to be effective in animal models of kidney injury. We hypothesized that paricalcitol could play a renoprotective role against CI-AKI. Rats were divided into control, paricalcitol, contrast, and paricalcitol-plus-contrast groups. We used a previously published protocol to produce CI-AKI. Paricalcitol (0.3 μg/kg) was administered intraperitoneally before 24 h and 30 min before indomethacin. We used HK-2 cells to evaluate the effects of paricalcitol on mitophagy and senescence. Ioversol triggered renal dysfunction, increasing blood urea nitrogen and serum creatinine. Significant tubular damage, increased 8-OHdG expression, and apoptosis were apparent. Ioversol injection induced high expression levels of the mitophagy markers Pink1, Parkin, and LC3 and the senescence markers β-galactosidase and p16INK4A. Paricalcitol pretreatment prevented renal dysfunction and reduced tissue damage by reducing both mitophagy and senescence. Cellular morphological changes were found, and expression of LC3B and HMGB1 was increased by ioversol in HK-2 cells. Paricalcitol countered these effects. This study showed that mitochondria might drive injury phenotypes in CI-AKI, and that paricalcitol protects against CI-AKI by decreasing mitochondrial damage.

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“…Under the stimulation of ischemia or nephrotoxic substances, the energy supply center of renal tubular epithelial cells is prone to damage, which is manifested by the decrease of mitochondrial membrane potential, the decrease of ATP production and the increase of ROS production (Cao et al., 2020). Recent studies have found that Nrf2 is involved in regulating mitochondrial function and stability (Zhao et al., 2020). First, Nrf2 participates in the regulation of mitochondrial membrane potential and respiratory chain and ATP synthesis substrate (Dinkova‐Kostova & Abramov, 2015).…”

Section: The Mechanism Of Aki and Nrf2mentioning

confidence: 99%

“…Contrast‐induced AKI (CI‐AKI) is an important clinical complication of intravascular use of iodinated contrast agents. Contrast agents downregulate the expression of Nrf2 and increase the production of ROS, thereby aggravating mitochondrial damage, oxidative stress, inflammation and apoptosis damage, leading to the occurrence of AKI (Zhao et al., 2020).…”

Section: The Protective Effect Of Nrf2 On Acute Kidney Injurymentioning

confidence: 99%

Protection against acute renal injury by naturally occurring medicines which act through Nrf2 signaling pathway

Wang

Luo

et al. 2020

J. Food Biochem.

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The cellular defense pathway plays a key role in maintaining the homeostasis, tissues and organisms. Nuclear factor E2-related factor 2 (Nrf2), as a key cell signaling pathway, plays an important role in encoding detoxification enzymes and other stress response mediators. Recent studies have shown that it is closely related to the prevention and treatment of acute kidney injury (AKI). Therefore, this article reviews the protective effects of Nrf2-related signaling pathways on acute kidney injury, and summarizes the strategies of natural pharmaceutical ingredients such as flavonoids, alkaloids, terpenes, phenylpropionic acid, polyphenols, and polysaccharides to prevent and treat acute kidney injury. It is of great significance to further study the relationship between Nrf2 regulated signal pathway and kidney disease and the development of new medicines for acute kidney injury treatment. It can also provide new ideas and treatment strategies for clinical treatment of acute kidney injury. Practical applications This article reviewed the mechanisms by which the active ingredients of natural medicines slow down acute kidney injury through the Nrf2 pathway. It will help us to understand the regulatory role of the Nrf2 pathway in AKI more comprehensively, and provide a theoretical basis for further exploring the mechanism of more natural drugs to reduce acute kidney injury.

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Stanniocalcin-1 Alleviates Contrast-Induced Acute Kidney Injury by Regulating Mitochondrial Quality Control via the Nrf2 Pathway

Cited by 13 publications

References 44 publications

Phillyrin Mitigates Apoptosis and Oxidative Stress in Hydrogen Peroxide-Treated RPE Cells through Activation of the Nrf2 Signaling Pathway

Phillyrin Mitigates Apoptosis and Oxidative Stress in Hydrogen Peroxide-Treated RPE Cells through Activation of the Nrf2 Signaling Pathway

Paricalcitol Attenuates Contrast-Induced Acute Kidney Injury by Regulating Mitophagy and Senescence

Protection against acute renal injury by naturally occurring medicines which act through Nrf2 signaling pathway

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