Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against cisplatin-induced acute kidney injury

Yang, Yunwen; Yu, Xiaowen; Zhang, Yue; Ding, Guofu; Zhu, Changlian; Huang, Songming; Jia, Zhanjun; Zhang, Aihua

doi:10.1042/cs20171625

Cited by 105 publications

(101 citation statements)

References 43 publications

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“…These studies support a protective role of FoxO3 during the AKI-to-CKD transition by reducing oxidative stress and increasing autophagy. The protective role of prolyl hydroxylation inhibition was also demonstrated in a study showing that the prolyl hydroxylase inhibitor roxadustat (FG-4592) afforded protection against cisplatin nephrotoxicity [191].…”

Section: Foxo3-mediated Autophagy Induction and Kidney Diseasementioning

confidence: 86%

“…↑ autophagy [191] Aristolochic acid (AA)-induced nephropathy AA exposure ↑ autophagy with ↑ ERK1/2 activity [192] UUO FoxO3 ↑ autophagy through nuclear expression of Atg proteins [193] Prolonged IR (AKI to CKD transition) FoxO3 ↑ autophagy [194] Ischemic preconditioning Increased FoxO3 by overexpression of SGK1 ↑ autophagy [196] Podocyte injury Aldosterone ↑ autophagy through FoxO1-Rab7 [195] STZ-induced DN FoxO1 overexpression ↑ autophagy [196] Podocyte injury Atrasentan ↑ autophagy by increased expression of FoxO1 by downregulating miR21 [197] 4.2.9. GCN2 Kinase-Mediated Autophagy Induction and Kidney Disease Another kinase, known as general control nonderepressible 2 (GCN2), is activated in response to deprivation of amino acids and induces autophagy [199].…”

Section: Model/ Kidney Disease Agent/drug Effect On Autophagy Referencementioning

confidence: 99%

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Autophagy Function and Regulation in Kidney Disease

et al. 2020

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Autophagy is a dynamic process by which intracellular damaged macromolecules and organelles are degraded and recycled for the synthesis of new cellular components. Basal autophagy in the kidney acts as a quality control system and is vital for cellular metabolic and organelle homeostasis. Under pathological conditions, autophagy facilitates cellular adaptation; however, activation of autophagy in response to renal injury may be insufficient to provide protection, especially under dysregulated conditions. Kidney-specific deletion of Atg genes in mice has consistently demonstrated worsened acute kidney injury (AKI) outcomes supporting the notion of a pro-survival role of autophagy. Recent studies have also begun to unfold the role of autophagy in progressive renal disease and subsequent fibrosis. Autophagy also influences tubular cell death in renal injury. In this review, we reported the current understanding of autophagy regulation and its role in the pathogenesis of renal injury. In particular, the classic mammalian target of rapamycin (mTOR)-dependent signaling pathway and other mTOR-independent alternative signaling pathways of autophagy regulation were described. Finally, we summarized the impact of autophagy activation on different forms of cell death, including apoptosis and regulated necrosis, associated with the pathophysiology of renal injury. Understanding the regulatory mechanisms of autophagy would identify important targets for therapeutic approaches.

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Section: Foxo3-mediated Autophagy Induction and Kidney Diseasementioning

confidence: 86%

Section: Model/ Kidney Disease Agent/drug Effect On Autophagy Referencementioning

confidence: 99%

Autophagy Function and Regulation in Kidney Disease

et al. 2020

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“…Serum levels of IL-6 and TNF-α were measured by ELISA kits (Dakewe Biotech, Beijing, China) in accordance with the manufacturer's instructions. The levels of Cystatin C in the serum were also determined by a mouse Cystatin C ELISA kit ( E -EL-M0389C, Elascience, China) [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

Celastrol ameliorates cisplatin nephrotoxicity by inhibiting NF-κB and improving mitochondrial function

Meng

et al. 2018

EBioMedicine

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149

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BackgroundCelastrol is an active ingredient of Chinese medicine Tripterygium wilfordii which is clinically used to treat the immune diseases. Currently, celastrol is documented as a potent agent for treating cancer and inflammatory disorders. This study was to investigate the effect of celastrol on cisplatin nephrotoxicity and the underlying mechanism.MethodsMale C57BL/6 mice were treated with cisplatin (20 mg/kg) with or without celastrol treatment (1 and 2 mg/kg/day). In vitro, human proximal tubule epithelial cell line (HK−2) and mouse renal tubule epithelial cells (RTECs) were treated with cisplatin (5 μg/mL) with or without celastrol administration. Then renal injury and cell damage were evaluated.FindingsIn vivo, after celastrol treatment, cisplatin-induced kidney injury was significantly ameliorated as shown by the improvement of renal function (BUN, serum creatinine, and cystatin C), kidney morphology (PAS staining) and oxidative stress (MDA) and the suppression of renal tubular injury markers of KIM-1 and NGAL. Meanwhile, the renal apoptosis and inflammation induced by cisplatin were also strikingly attenuated in celastrol-treated mice. In vitro, celastrol treatment markedly inhibited cisplatin-induced renal tubular cell apoptosis, suppressed NF-κB activation, and improved mitochondrial function evidenced by the restored mtDNA copy number, mitochondrial membrane potential, and OXPHOS activity in cisplatin-treated renal tubular epithelial cells.InterpretationThis work suggested that celastrol could protect against cisplatin-induced acute kidney injury possibly through suppressing NF-κB and improving mitochondrial function.FundThe National Natural Science Foundation of China, National Key Research and Development Program, and Natural Science Foundation of Jiangsu Province.

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“…It has been reported in the literature that the incidence of AKI after APAP overdose is 2%~10% (Reshi et al, ). KIM‐1, NGAL, and Cys‐C are considered to be reliable renal biomarkers, which are normally not expressed in normal kidney tissues, but are highly expressed when they are damaged by kidney toxicity or ischemia (Soetikno et al, ; Yang, et al, ). Therefore, our results indicate that SDAPR retains HK‐2 cells in APAP‐induced nephrotoxicity to some extent.…”

Section: Discussionmentioning

confidence: 99%

“…(Sui, Zhang, Huo, & Zhang, ). According to reports, sika deer antler protein (SDAPR) can protect cisplatin‐induced and gentamicin‐induced AKI (Sun et al, ; Yang et al, ). The study also showed that antlers can resist LPS‐induced acute lung injury by activating AMPK/Nrf2 pathway (Chang et al, ).…”

Section: Introductionmentioning

confidence: 99%

Sika deer antler protein against acetaminophen‐induced oxidative stress and apoptosis in HK‐2 cells via activating Nrf2/keap1/HO‐1 pathway

Ruan

Wang

et al. 2019

J Food Biochem

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Nf-E2-related transcription factor 2 (Nrf2) helps cells fight oxidative stress events in vivo and in vitro by promoting the expression of antioxidants and detoxification enzymes. The necessary factors regulating Nrf2 activity and stability during analgesic nephropathy are not fully understood. Our results suggest that acetaminophen produces nephrotoxicity in HK-2 cells by inhibiting keap1 degradation. APAP subsided Nrf2 nuclear accumulation by inhibition of keap1 degradation, thereby reducing the binding of Nrf2 to ARE, leading to the loss of expression of antioxidant proteins such as HO-1, inducing a series of oxidative stress and apoptosis events. Therefore, Nrf2/ keap1/HO-1 signal transduction pathway has a poor prognosis during analgesic nephrotoxicity. Sika deer antler protein (SDAPR) significantly prevented APAP-induced HK-2 cell damage by constitutively stabilized Nrf2 nuclear retention. Excess APAP leads to a decrease in Nrf2 nuclear translocation, leading to severe oxidative stress, increasing the levels of GSH and MDA in HK-2 cells, and reducing the enzyme activities of SOD and CAT in HK-2 cells. Increased biomarker levels of acute kidney injury (AKI) in HK-2 cells, including kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and cystatin C, decrease the mitochondrial membrane potential in HK-2 cells, and cause mitochondrial dysfunction, it also reduced the ratio of mitochondria-associated apoptotic protein Bax/Bcl-2, leading to cell apoptosis. SDAPR dose dependently accorded protection against acetaminophen-induced nephrotoxicity, oxidative damage, and cell apoptosis by its molecular intervention with Nrf2/ keap1/HO-1 pathway via keap1 degradation. Practical applicationsIn this paper, we investigated the protective effect of SDAPR on APAP-induced AKI in HK-2 cells, and briefly explained its possible mechanism of action, providing a basis for future clinical trials and the development of anti-APAP AKI drugs. K E Y W O R D S acetaminophen, apoptosis, HK-2 cell, Nrf2/keap1/HO-1 pathway, oxidative stress, sika deer antler protein How to cite this article: Ruan H, Wang L, Wang J, et al. Sika deer antler protein against acetaminophen-induced oxidative stress and apoptosis in HK-2 cells via activating Nrf2/keap1/ HO-1 pathway. J Food Biochem. 2019;43:e13067.

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Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against cisplatin-induced acute kidney injury

Cited by 105 publications

References 43 publications

Autophagy Function and Regulation in Kidney Disease

Autophagy Function and Regulation in Kidney Disease

Celastrol ameliorates cisplatin nephrotoxicity by inhibiting NF-κB and improving mitochondrial function

Sika deer antler protein against acetaminophen‐induced oxidative stress and apoptosis in HK‐2 cells via activating Nrf2/keap1/HO‐1 pathway

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