Hexavalent chromium induced heart dysfunction via Sesn2-mediated impairment of mitochondrial function and energy supply

Yang, Daqian; Yang, Qingyue; Fu, Ning; Li, Siyu; Han, Bing; Liu, Yan; Tang, Yongming; Guo, Xinyu; Lv, Zhanjun; Zhang, Zhigang

doi:10.1016/j.chemosphere.2020.128547

Cited by 72 publications

(41 citation statements)

References 76 publications

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“…Under homeostatic conditions, Nrf2, anchored in the cytoplasm, is ubiquitinated and continuously degraded [ 48 ]. When the body encounters stresses, Nrf2 is released into the nucleus, binding to the ARE sequence of the downstream target genes to promote the expression of phase II detoxification enzymes, including NQO1 and HO-1, which can alleviate mitochondrial dysfunction and resist excessive oxidative stress [ 49 ]. Furthermore, inhibition of Nrf2 can not only result in TLR4/NF κ B-mediated proinflammatory response [ 50 ], but also promote fibrosis via the activation of TGF- β 1/Smad pathway [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Huayu Tongluo Recipe Attenuates Renal Oxidative Stress and Inflammation through the Activation of AMPK/Nrf2 Signaling Pathway in Streptozotocin- (STZ-) Induced Diabetic Rats

Guo

Yang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Diabetic nephropathy (DN), a severe microvascular complication of diabetes, is one of the leading causes of end-stage renal disease. Huayu Tongluo Recipe (HTR) has been widely used in the clinical treatment of DN in China, and its efficacy is reliable. This study aimed to explore the renoprotective effect of HTR and the underlying mechanism. Male Sprague-Dawley rats were fed with high sugar and fat diet combined with an intraperitoneal injection of STZ to establish the diabetic model. Rats in each group were respectively given drinking water, HTR, and irbesartan by gavage for 16 weeks. 24-hour urine samples were collected every 4 weeks to detect the content of total protein and 8-OHdG. Blood samples were taken to detect biochemical indicators and inflammatory markers at the end of 16th week. Renal tissue was collected to investigate pathological changes and to detect oxidative stress and inflammatory markers. AMPK/Nrf2 signaling pathway and fibrosis-related proteins were detected by immunohistochemistry, immunofluorescence, real-time PCR, and western blot. 24h urine total protein (24h UTP), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), and triglyceride (TG) were decreased in the rats treated with HTR, while there was no noticeable change of blood glucose. HTR administration decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity in kidneys, complying with reduced 8-OHdG in the urine. The levels of TNF-α, IL-1β, and MCP1 and the expression of nuclear NFκB were also lower after HTR treatment. Furthermore, HTR alleviated pathological renal injury and reduced the accumulation of extracellular matrix (ECM). Besides, HTR enhanced the AMPK/Nrf2 signaling and increased the expression of HO-1 while it inhibited the Nox4/TGF-β1 signaling in the kidneys of STZ-induced diabetic rats. HTR can inhibit renal oxidative stress and inflammation to reduce ECM accumulation and protect the kidney through activating the AMPK/Nrf2 signaling pathway in DN.

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Section: Discussionmentioning

confidence: 99%

Huayu Tongluo Recipe Attenuates Renal Oxidative Stress and Inflammation through the Activation of AMPK/Nrf2 Signaling Pathway in Streptozotocin- (STZ-) Induced Diabetic Rats

Guo

Yang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Accumulating evidence demonstrates that the intake of toxic agents (such as uric acid, oxalic acid and heavy metals) might lead to cell antioxidant defense dysfunction and apoptosis (49)(50)(51); however, the exact mechanism of apoptosis caused by UA-induced antioxidant imbalance requires further study. There have been a number of studies on the mechanism of UA-mediated ROS-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway

Wang

et al. 2021

Mol Med Rep

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increasing uric acid (ua) could induce renal tubular epithelial cell (NRK-52E) injury. However, the specific mechanism by which UA induces renal tubular epithelial cell injury remains unknown. It was hypothesized that UA induces renal tubular epithelial cell injury through reactive oxygen species (ROS) and the Never in mitosis gene A (NIMA)-related kinase 7 (NEK7)/NLR family pyrin domain containing 3 (NLRP3) signaling pathway. TUNEL assay and flow cytometry were applied to measure apoptosis, and the results of the present study showed that UA treatment induced apoptosis of NRK-52E cells in a concentration-dependent manner. Western blotting was performed to determine the expression levels of cleaved caspase-3, Bax and Bcl-xl, it was found that levels were significantly increased after UA treatment in NRK-52E cells. ROS and apoptosis were predominantly induced in NRK-52E cells and there was an association between roS and apoptosis. Enhanced expression of NEK7, NLRP3, apoptosis-associated speck-like and caspase-1 were observed in NRK-52E cells treated with ua. The roS inhibitor, n-acetyl-l-cysteine, exerted a protective effect on the UA-induced apoptosis of tubular epithelial cells by reducing excess roS production, which significantly inhibited NEK7 and NLRP3 inflammasome activation. These results indicated that UA activates ROS and induces apoptosis of NRK-52E cells. The mechanism might be related to the regulation of the NEK7/NLRP3 signaling pathway.

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“…Lastly, it should be noted that in addition to HO-1, Nrf2 can transcriptionally induce a variety of antioxidative genes including NAD(P) H dehydrogenase quinone 1 (NQO-1). It has been demonstrated that NQO-1 plays a critical role in monitoring cellular redox state and protects against oxidative stress induced by a variety of metabolic situations [56,57]. Whether NQO-1 is involved in the beneficial effects of LUT against SAH remains obscure.…”

Section: Discussionmentioning

confidence: 99%

Luteolin Confers Cerebroprotection after Subarachnoid Hemorrhage by Suppression of NLPR3 Inflammasome Activation through Nrf2‐Dependent Pathway

Zhang

Liu

et al. 2021

Oxidative Medicine and Cellular Longevity

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Luteolin (LUT) possesses multiple biologic functions and has beneficial effects for cardiovascular and cerebral vascular diseases. Here, we investigated the protective effects of LUT against subarachnoid hemorrhage (SAH) and the involvement of underlying molecular mechanisms. In a rat model of SAH, LUT significantly inhibited SAH-induced neuroinflammation as evidenced by reduced microglia activation, decreased neutrophil infiltration, and suppressed proinflammatory cytokine release. In addition, LUT markedly ameliorated SAH-induced oxidative damage and restored the endogenous antioxidant systems. Concomitant with the suppressed oxidative stress and neuroinflammation, LUT significantly improved neurologic function and reduced neuronal cell death after SAH. Mechanistically, LUT treatment significantly enhanced the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), while it downregulated nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation. Inhibition of Nrf2 by ML385 dramatically abrogated LUT-induced Nrf2 activation and NLRP3 suppression and reversed the beneficial effects of LUT against SAH. In neurons and microglia coculture system, LUT also mitigated oxidative stress, inflammatory response, and neuronal degeneration. These beneficial effects were associated with activation of the Nrf2 and inhibitory effects on NLRP3 inflammasome and were reversed by ML385 treatment. Taken together, this present study reveals that LUT confers protection against SAH by inhibiting NLRP3 inflammasome signaling pathway, which may be modulated by Nrf2 activation.

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Hexavalent chromium induced heart dysfunction via Sesn2-mediated impairment of mitochondrial function and energy supply

Cited by 72 publications

References 76 publications

Huayu Tongluo Recipe Attenuates Renal Oxidative Stress and Inflammation through the Activation of AMPK/Nrf2 Signaling Pathway in Streptozotocin- (STZ-) Induced Diabetic Rats

Huayu Tongluo Recipe Attenuates Renal Oxidative Stress and Inflammation through the Activation of AMPK/Nrf2 Signaling Pathway in Streptozotocin- (STZ-) Induced Diabetic Rats

Reactive oxygen species induced by uric acid promote NRK‑52E cell apoptosis through the NEK7‑NLRP3 signaling pathway

Luteolin Confers Cerebroprotection after Subarachnoid Hemorrhage by Suppression of NLPR3 Inflammasome Activation through Nrf2‐Dependent Pathway

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