scholarly journals Glaucocalyxin A Ameliorates Hypoxia/Reoxygenation-Induced Injury in Human Renal Proximal Tubular Epithelial Cell Line HK-2 Cells

2021 ◽  
Vol 23 (1) ◽  
pp. 446
Author(s):  
Keiko Hosohata ◽  
Denan Jin ◽  
Shinji Takai
Keyword(s):  
Cell Death ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Therapeutic Drug ◽  
Epithelial Cell Line ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Ros Production ◽  
Hypoxia Reoxygenation

Ischemia-reperfusion injury is one of the major causes of acute kidney injury (AKI), which is increasingly prevalent in clinical settings. Glaucocalxin A (GLA), a biologically ent-kauranoid diterpenoid, has various pharmacological effects like antioxidation, immune regulation, and antiatherosclerosis. In this study, the effect of GLA on AKI and its mechanism were studied in vitro. HK-2 human renal tubular epithelial cells were exposed to hypoxia/reoxygenation (H/R), which were established as an in vitro AKI model. Subsequently, the mRNA expressions of inflammatory and antioxidant factors were determined by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Reactive oxygen species (ROS) production and cell death were detected by fluorescence-activated cell sorting. GLA pre-treatment improved the cell viability of HK-2 cells exposed to H/R. GLA suppressed the H/R-induced ROS production in HK-2 cells. GLA also elevated the activities of superoxide dismutase of HK-2 cells exposed to H/R. Moreover, GLA prevented H/R-induced cell death in HK-2 cells. Furthermore, GLA ameliorated the activation of the protein kinase B (Akt)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in HK-2 cells exposed to H/R. Our findings suggested that GLA protected HK-2 cells from H/R-induced oxidative damage, which was mediated by the Akt/Nrf2/HO-1 signaling pathway. These results indicate that GLA may serve as a promising therapeutic drug for AKI.

scholarly journals Glaucocalyxin A Protects H9c2 Cells Against Hypoxia/Reoxygenation-Induced Injury Through the Activation of Akt/Nrf2/HO-1 Pathway

2020 ◽  
Vol 29 ◽  
pp. 096368972096767
Author(s):  
Zhuo Peng ◽  
Rui Zhang ◽  
Longfei Pan ◽  
Honghong Pei ◽  
Zequn Niu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Biologically Active ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
H9c2 Cells ◽  
Rat Cardiomyocytes ◽  
Myocardial Ischemia Reperfusion ◽  
Hypoxia Reoxygenation

Myocardial infarction (MI) is one of the most serious cardiovascular diseases associated with myocardial ischemia/reperfusion (I/R) injury. Glaucocalyxin A (GLA) is a biologically active ent-kauranoid diterpenoid that has been found to ameliorate myocardial I/R injury in mice. However, the mechanism has not been fully investigated. In the present study, we aimed to investigate the effect of GLA on rat cardiomyocytes H9c2 cells exposed to hypoxia/reoxygenation (H/R). The results showed that GLA treatment improved cell viability of H/R-stimulated H9c2 cells. Administration with GLA suppressed the H/R-stimulated reactive oxygen species (ROS) production in H9c2 cells. GLA also elevated the activities of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase in H/R-stimulated H9c2 cells. Moreover, GLA prevented H/R-stimulated cell apoptosis in H9c2 cells, as evidenced by increased bcl-2 expression, decreased bax expression, as well as reduced caspase-3 activity. Furthermore, GLA enhanced the activation of protein kinase B (Akt)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in H9c2 cells exposed to H/R. Additionally, treatment with LY294002 reserved the protective effects of GLA on H/R-stimulated oxidative injury in H9c2 cells. In conclusion, these findings suggested that GLA protected H9c2 cells from H/R-stimulated oxidative damage, which was mediated by the Akt/Nrf2/HO-1 signaling pathway. Thus, GLA might be a promising therapeutic agent for the prevention and treatment of myocardial I/R.

scholarly journals Knockdown of ANGPTL2 Protects Renal Tubular Epithelial Cells Against Hypoxia/Reoxygenation-Induced Injury via Suppressing TLR4/NF-κB Signaling Pathway and Activating Nrf2/HO-1 Signaling Pathway

2020 ◽  
Vol 29 ◽  
pp. 096368972094666
Author(s):  
Heli Xiang ◽  
Wujun Xue ◽  
Yang Li ◽  
Jin Zheng ◽  
Chenguang Ding ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Tubular Epithelial Cell ◽  
Epithelial Cell Line ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Treatment And Prevention ◽  
Renal Tubular ◽  
Hypoxia Reoxygenation

Renal ischemia/reperfusion (I/R) injury is a particular threat faced by clinicians in kidney transplantation. Previous studies have confirmed the importance of oxidative stress and inflammation in the pathogenesis of I/R injury. Angiopoietin-like protein 2 (ANGPTL2) belongs to the angiopoietin-like family and has been found to be involved in the regulation of kidney function as well as oxidative and inflammatory response. In the present study, we aimed to evaluate the role of ANGPTL2 in renal I/R injury in vitro. The human proximal tubular epithelial cell line (HK-2 cells) was subjected to hypoxia/ reoxygenation (H/R) to mimic I/R injury in vitro. We found that the expression level of ANGPTL2 was markedly increased in H/R-induced HK-2 cells. Knockdown of ANGPTL2 improved the decreased cell viability of HK-2 cells in response to H/R stimulation. Knockdown of ANGPTL2 significantly inhibited the H/R-caused increase in levels of reactive oxygen species, malondialdehyde, and proinflammatory cytokines, including interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha, as well as a decrease in superoxide dismutase activity in the HK-2 cells. Besides, the increased bax expression and caspase-3 activity and decreased bcl-2 expression in H/R-induced HK-2 cells were also attenuated by knockdown of ANGPTL2. Moreover, ANGPTL2 overexpression showed the opposite effects. Further mechanism investigations proved that the activation of Nrf2/HO-1 signaling pathway and the inhibition of toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway were both implicated in the renal-protective effects of ANGPTL2 knockdown on H/R-induced HK-2 cells. Collectively, these findings suggested that ANGPTL2 might be a new possible target for the treatment and prevention of renal I/R injury.

scholarly journals Ginsenoside Rb1 Treatment Attenuates Pulmonary Inflammatory Cytokine Release and Tissue Injury following Intestinal Ischemia Reperfusion Injury in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Ying Jiang ◽  
Zhen Zhou ◽  
Qing-tao Meng ◽  
Qian Sun ◽  
Wating Su ◽  
...  
Keyword(s):  
Lung Injury ◽  
Signaling Pathway ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Weight Ratio ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Ginsenoside Rb1 ◽  
Intestinal Ischemia Reperfusion

Objective. Intestinal ischemia reperfusion (II/R) injury plays a critical role in remote organ dysfunction, such as lung injury, which is associated with nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In the present study, we tested whether ginsenoside Rb1 attenuated II/R induced lung injury by Nrf2/HO-1 pathway.Methods. II/R injury was induced in male C57BL/6J mice by 45 min of superior mesenteric artery (SMA) occlusion followed by 2 hours of reperfusion. Ginsenoside Rb1 was administrated prior to reperfusion with or without ATRA (all-transretinoic acid, the inhibitor of Nrf2/ARE signaling pathway) administration before II/R.Results. II/R induced lung histological injury, which is accompanied with increased levels of malondialdehyde (MDA), interleukin- (IL-) 6, and tumor necrosis factor- (TNF-)αbut decreased levels of superoxide dismutase (SOD) and IL-10 in the lung tissues. Ginsenoside Rb1 reduced lung histological injury and the levels of TNF-αand MDA, as well as wet/dry weight ratio. Interestingly, the increased Nrf2 and HO-1 expression induced by II/R in the lung tissues was promoted by ginsenoside Rb1 treatment. All these changes could be inhibited or prevented by ATRA.Conclusion. Ginsenoside Rb1 is capable of ameliorating II/R induced lung injuries by activating Nrf2/HO-1 pathway.

Cpt1a promoted ROS-induced oxidative stress and inflammation in liver injury via the Nrf2/HO-1 and NLRP3 inflammasome signaling pathway

2020 ◽  
Author(s):  
Xigang Luo ◽  
Dapeng Sun ◽  
Yinxiang Wang ◽  
Fengxiang Zhang ◽  
Yi Wang
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Nlrp3 Inflammasome ◽  
Receptor Protein ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Over Expression ◽  
Vitro Model

Various liver diseases caused by liver damage seriously affect people’s health. The purpose of this study was to clarify that the effects and mechanism of Carnitine palmitoyltransferase 1 (Cpt1a) on oxidative stress and inflammation in liver injury. It was found that the expression of Cpt1a mRNA was up-regulated in model mice of liver injury. So, over-expression of Cpt1a increased reactive oxygen species (ROS) production and malondialdehyde (MDA) levels, and reduced superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-px) levels in vitro model of liver injury. It was also shown that over-expression of Cpt1a suppressed the Nuclear factor-erythroid-2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) signaling pathway. In summary, these data indicate that Cpt1a promotes ROS-induced oxidative stress in liver injury via the Nrf2/HO-1 and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome signaling pathway.

scholarly journals Attenuation ofβ-Amyloid-Induced Oxidative Cell Death by Sulforaphane via Activation of NF-E2-Related Factor 2

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Chan Lee ◽  
Gyu Hwan Park ◽  
Seong-Ryong Lee ◽  
Jung-Hee Jang
Keyword(s):  
Cell Death ◽  
Apoptotic Cell ◽  
Senile Plaques ◽  
Amyloid Peptide ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Altered Expression ◽  
Nrf2 Signaling Pathway

β-amyloid peptide (Aβ), a major component of senile plaques, plays important roles in neuropathology of Alzheimer's disease (AD). An array ofin vitroandin vivodata indicates that Aβ-induced neuronal death is mediated by oxidative stress. In this study, we aimed to investigate effects of sulforaphane (SUL), an isothiocyanate in cruciferous vegetables, on Aβ-induced oxidative cell death in SH-SY5Y cells. Cells treated with Aβ25–35exhibited decreased cell viability and underwent apoptosis as determined by MTT assay and TUNEL, respectively. Aβ25–35-induced cytotoxicity and apoptotic characteristics such as activation of c-JNK, dissipation of mitochondrial membrane potential, altered expression of Bcl-2 family proteins, and DNA fragmentation were effectively attenuated by SUL pretreatment. The antiapoptotic activity of SUL seemed to be mediated by inhibition of intracellular accumulation of reactive oxygen species and oxidative damages. SUL exerted antioxidant potential by upregulating expression of antioxidant enzymes includingγ-glutamylcysteine ligase, NAD(P)H:quinone oxidoreductase-1, and heme oxygenase-1 via activation of NF-E2-related factor 2(Nrf2). The protective effect of SUL against Aβ25–35-induced apoptotic cell death was abolished by siRNA of Nrf2. Taken together, the results suggest that pharmacologic activation of Nrf2 signaling pathway by SUL might be a practical prevention and/or protective treatment for the management of AD.

scholarly journals Oleanolic Acid Alleviates Cerebral Ischemia/Reperfusion Injury via Regulation of the GSK-3β/HO-1 Signaling Pathway

2021 ◽  
Vol 15 (1) ◽  
pp. 1
Author(s):  
Kaili Lin ◽  
Zhang Zhang ◽  
Zhu Zhang ◽  
Peili Zhu ◽  
Xiaoli Jiang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathway ◽  
Oleanolic Acid ◽  
Ischemia Reperfusion Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Heme Oxygenase 1 ◽  
Therapeutic Effects ◽  
Gsk 3Β

Oleanolic acid (OA), a bioactive ingredient of Panax ginseng, exhibits neuroprotective pharmacological effects. However, the protective role of OA in cerebral ischemia and involved mechanisms remain unclear. This study attempted to explore the therapeutic effects of OA both in vitro and in vivo. OA attenuated cytotoxicity and overproduction of intracellular reactive oxygen species (ROS) by regulation of glycogen synthase kinase-3β (GSK-3β)/heme oxygenase-1 (HO-1) signal in oxygen-glucose deprivation/reoxygenation (OGD/R)-exposed SH-SY5Y cells. Additionally, OA administration significantly reduced the area of cerebral infarction and the neurological scores in the rat models of cerebral ischemia with middle cerebral artery occlusion (MCAO). The OA administration group showed a higher percentage of Nissl+ and NeuN+ cells, along with lower TUNEL+ ratios in the infarct area of MCAO rats. Moreover, OA administration reduced ROS production while it suppressed the GSK-3β activation and upregulated the HO-1 expression in infarcted tissue. Our results illustrated that OA significantly counteracted cerebral ischemia-mediated injury through antioxidant effects induced by the regulation of the GSK-3β/HO-1 signaling pathway, implicating OA as a promising neuroprotective drug for the therapy of ischemic stroke.

scholarly journals (Pro)renin Receptor Contributes to Hypoxia/Reoxygenation-Induced Apoptosis and Autophagy in Myocardial Cells via the β-Catenin Signaling Pathway

2020 ◽  
pp. 427-438
Author(s):  
X GAO ◽  
S ZHANG ◽  
D WANG ◽  
Y CHENG ◽  
Y JIANG ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Counting ◽  
H9c2 Cells ◽  
Related Factors ◽  
Myocardial Ischemia Reperfusion ◽  
Induced Apoptosis ◽  
Hypoxia Reoxygenation

(Pro)renin receptor (PRR) contributes to regulating many physiological and pathological processes; however, the role of PRR-mediated signaling pathways in myocardial ischemia/reperfusion injury (IRI) remains unclear. In this study, we used an in vitro model of hypoxia/reoxygenation (H/R) to mimic IRI and carried out PRR knockdown by siRNA and PRR overexpression using cDNA in H9c2 cells. Cell proliferation activity was examined by MTT and Cell Counting Kit-8 (CCK-8) assays. Apoptosis-related factors, autophagy markers and β-catenin pathway activity were assessed by real-time PCR and western blotting. After 24 h of hypoxia followed by 2 h of reoxygenation, the expression levels of PRR, LC3B-I/II, Beclin1, cleaved caspase-3, cleaved caspase-9 and Bax were upregulated, suggesting that apoptosis and autophagy were increased in H9c2 cells. Contrary to the effects of PRR downregulation, the overexpression of PRR inhibited proliferation, induced apoptosis, increased the expression of pro-apoptotic factors and autophagy markers, and promoted activation of the β-catenin pathway. Furthermore, all these effects were reversed by treatment with the β-catenin antagonist DKK-1. Thus, we concluded that PRR activation can trigger H/R-induced apoptosis and autophagy in H9c2 cells through the β-catenin signaling pathway, which may provide new therapeutic targets for the prevention and treatment of myocardial IRI.

scholarly journals Identification of MicroRNA-92a-3p as an Essential Regulator of Tubular Epithelial Cell Pyroptosis by Targeting Nrf1 via HO-1

2021 ◽  
Vol 11 ◽  
Author(s):  
Renhe Wang ◽  
Haijun Zhao ◽  
Yingyu Zhang ◽  
Hai Zhu ◽  
Qiuju Su ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cell ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Tubular Epithelial Cell ◽  
Heme Oxygenase 1 ◽  
Related Factor

Renal ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and has no effective treatment. Exploring the molecular mechanisms of renal IRI is critical for the prevention of AKI and its evolution to chronic kidney disease and end-stage renal disease. The aim of the present study was to determine the biological function and molecular mechanism of action of miR-92a-3p in tubular epithelial cell (TEC) pyroptosis. We investigated the relationship between nuclear factor-erythroid 2-related factor 1 (Nrf1) and TEC pyroptosis induced by ischemia–reperfusion in vivo and oxygen–glucose deprivation/reoxygenation (OGD/R) in vitro. MicroRNAs (miRNAs) are regulators of gene expression and play a role in the progression of renal IRI. Nrf1 was confirmed as a potential target for miRNA miR-92a-3p. In addition, the inhibition of miR-92a-3p alleviated oxidative stress in vitro and decreased the expression levels of NLRP3, caspase-1, GSDMD-N, IL-1β, and IL-18 in vitro and in vivo. Moreover, Zn-protoporphyrin-IX, an inhibitor of heme oxygenase-1, reduced the protective effect of Nrf1 overexpression on OGD/R-induced TEC oxidative stress and pyroptosis. The results of this study suggest that the inhibition of miR-92a-3p can alleviate TEC oxidative stress and pyroptosis by targeting Nrf1 in renal IRI.

1-Bromopropane-induced apoptosis in OVCAR-3 cells via oxidative stress and inactivation of Nrf2

2020 ◽  
pp. 074823372097942
Author(s):  
Guangtao Yang ◽  
Yingping Xiang ◽  
Wei Zhou ◽  
Xiaohuan Zhong ◽  
Yanfang Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Reproductive Toxicity ◽  
Antioxidant Vitamin ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Ovarian Carcinoma Cell Line ◽  
Nrf2 Signaling Pathway ◽  
Induced Apoptosis

The bromoalkane, 1-bromopropane (1-BP), may damage the reproductive system though oxidative stress, while the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in regulating intracellular antioxidant levels against oxidative stress. This study explored the role of oxidative stress and the Nrf2 signaling pathway in mediating the reproductive toxicity of 1-BP using the ovarian carcinoma cell line OVCAR-3 as an in vitro model of the human ovary. OVCAR-3 cells were treated with 1, 5, 10 and 15 mM 1-BP. After 24 h, the cellular reactive oxygen species and malondialdehyde concentrations significantly increased, while the superoxide dismutase activity decreased; translocation of Nrf2 from the cytosol to the nucleus as well as downstream protein expression of Nrf2-regulated genes heme oxygenase-1 and Bcl-2 was inhibited. Apoptosis was also observed, accompanied by increased caspase-3 and caspase-9 activity. The antioxidant vitamin C alleviated 1-BP-induced apoptosis by inhibiting caspase activity activating the Nrf2 signaling pathway. These findings suggested that 1-BP induced oxidative stress and apoptosis in OVCAR-3 cells through inactivation of Nrf2 signaling.

scholarly journals Luteolin Attenuates Cardiac Ischemia/Reperfusion Injury in Diabetic Rats by Modulating Nrf2 Antioxidative Function

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Chi Xiao ◽  
Man-Li Xia ◽  
Jue Wang ◽  
Xin-Ru Zhou ◽  
Yang-Yun Lou ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Isolated Rat Heart ◽  
Diabetic Heart ◽  
Diabetic Rat ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nrf2 Signaling Pathway

Luteolin has been reported to attenuate ischemia/reperfusion (I/R) injury in the diabetic heart through endothelial nitric oxide synthase- (eNOS-) related antioxidative response. Though the nuclear factor erythroid 2-related factor 2 (Nrf2) is regarded as a key endogenous factor to reduce diabetic oxidative stress, whether luteolin reduces cardiac I/R injury in the diabetic heart via enhancing Nrf2 function needs to be clarified. We hypothesized that pretreatment with luteolin could alleviate cardiac I/R injury in the diabetic heart by affecting the eNOS/Nrf2 signaling pathway. The diabetic rat was produced by a single injection of streptozotocin (65 mg/kg, i.p.) for 6 weeks, and then, luteolin (100 mg/kg/day, i.g.), eNOS inhibitor L-NAME, or Nrf2 inhibitor brusatol was administered for the succedent 2 weeks. After that, the isolated rat heart was exposed to 30 min of global ischemia and 120 min of reperfusion to establish I/R injury. Luteolin markedly ameliorated cardiac function and myocardial viability; upregulated expressions of heme oxygenase-1, superoxide dismutase, glutathione peroxidase, and catalase; and reduced myocardial lactate dehydrogenase release, malondialdehyde, and 8-hydroxydeoxyguanosine in the diabetic I/R heart. All these ameliorating effects of luteolin were significantly reversed by L-NAME or brusatol. Luteolin also markedly reduced S-nitrosylation of Kelch-like ECH-associated protein 1 (Keap1) and upregulated Nrf2 and its transcriptional activity. This effect of luteolin on Keap1/Nrf2 signaling was attenuated by L-NAME. These data reveal that luteolin protects the diabetic heart against I/R injury by enhancing eNOS-mediated S-nitrosylation of Keap1, with subsequent upregulation of Nrf2 and the Nrf2-related antioxidative signaling pathway.

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