Nrf2 is not required for epithelial prohibitin-dependent attenuation of experimental colitis

Inflammatory bowel disease is associated with increased reactive oxygen species (ROS) and decreased antioxidant response in the intestinal mucosa. Expression of the mitochondrial protein prohibitin (PHB) is also decreased during intestinal inflammation. Our previous study showed that genetic restoration of colonic epithelial PHB expression [villin-PHB transgenic (PHB Tg) mice] attenuated dextran sodium sulfate (DSS)-induced colitis/oxidative stress and sustained expression of colonic nuclear factor erythroid 2-related factor 2 (Nrf2), a cytoprotective transcription factor. This study investigated the role of Nrf2 in mediating PHB-induced protection against colitis and expression of the antioxidant response element (ARE)-regulated antioxidant genes heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase-1 (NQO-1). PHB-transfected Caco-2-BBE human intestinal epithelial cells maintained increased ARE activation and decreased intracellular ROS levels compared with control vector-transfected cells during Nrf2 knockdown by small interfering RNA. Treatment with the ERK inhibitor PD-98059 decreased PHB-induced ARE activation, suggesting that ERK constitutes a significant portion of PHB-mediated ARE activation in Caco-2-BBE cells. PHB Tg, Nrf2−/−, and PHB Tg/Nrf2−/− mice were treated with DSS or 2,4,6-trinitrobenzene sulfonic acid (TNBS), and inflammation and expression of HO-1 and NQO-1 were assessed. PHB Tg/Nrf2−/− mice mimicked PHB Tg mice, with attenuated DSS- or TNBS-induced colitis and induction of colonic HO-1 and NQO-1 expression, despite deletion of Nrf2. PHB Tg/Nrf2−/− mice exhibited increased activation of ERK during colitis. Our results suggest that maintaining expression of intestinal epithelial cell PHB, which is decreased during colitis, reduces the severity of inflammation and increases colonic levels of the antioxidants HO-1 and NQO-1 via a mechanism independent of Nrf2.

Download Full-text

Upregulation of antioxidant nuclear factor erythroid 2-related factor 2 and its dependent genes associated with enhancing renal ischemic preconditioning renoprotection using levosimendan and cilostazol in an ischemia/reperfusion rat model

Archives of Medical Science ◽

10.5114/aoms/111373 ◽

2021 ◽

Vol 18 (2) ◽

pp. 1-34

Author(s):

Mona Tawfik ◽

Samy Makary ◽

Mohammed Keshawy

Keyword(s):

Ischemic Preconditioning ◽

Rat Model ◽

Ischemia Reperfusion ◽

Blood Oxygenation ◽

Renal Ischemia ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Quinone Oxidoreductase ◽

Antioxidant Genes

IntroductionIschemic preconditioning (Ipre) provides protection against renal ischemia-reperfusion (I/R) injury with its associated remote organ damage. This study examined the enhancing protective effect of Ipre with levosimendan or cilostazol in I/R-induced kidney and lung injury in a rat model.Material and methodsRats were divided into: sham-operated, I/R control, Ipre control, I/R + cilostazol or levosimendan and Ipre + cilostazol or levosimendan. Drugs were given 30 min before left renal I/R or 4 cycles of Ipre just before renal ischemia.ResultsThe Ipre combined with the implemented drugs enhanced physiological antioxidant defense genes including renal nuclear factor erythroid 2-related factor 2 (Nrf2) and its dependent genes heme oxygenase-1 (HO-1) and NADPH-quinone oxidoreductase-1 (NQO-1) and improved malondialdehyde and superoxide dismutase renal tissue levels. The combined effect improved I/R consequences for blood urea, creatinine, and creatinine clearance and improved blood oxygenation and metabolic acidosis. Moreover, the combination improved the renal soluble intercellular adhesion molecule (ICAM), tumor necrosis factor α (TNF-α) and interlukin-6 (IL-6) with histopathological improvement of tubular necrosis with a decrease in the apoptotic marker caspase-3 and an increase in the anti-apoptotic Bcl-2 expression.ConclusionsCilostazol or levosimendan potentiates the renoprotective effect of Ipre against renal I/R injury, associated with upregulation of antioxidant genes Nrf2, HO-1, and NOQ-1 expression.

Download Full-text

Cytoprotective Effect of Ligustrum robustum Polyphenol Extract against Hydrogen Peroxide-Induced Oxidative Stress via Nrf2 Signaling Pathway in Caco-2 Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/5026458 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Jiayi Chen ◽

Fangting He ◽

Sijing Liu ◽

Tao Zhou ◽

Saira Baloch ◽

...

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Signaling Pathway ◽

Total Phenolic ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Cytoprotective Effect ◽

Quinone Oxidoreductase ◽

Antioxidant Genes ◽

Nrf2 Signaling Pathway

Ligustrum robustum is a traditional herbal tea that is widely distributed in southwest China. The health effects of L. robustum are characteristics of clearing heat, antioxidant, inducing resurgence, and improving digestion. However, the molecular mechanisms related to these effects, particularly the antioxidant mechanism, have been seldom reported. The objective of this study was to assess antioxidative capacity of L. robustum, and its protective effects and mechanisms against hydrogen peroxide (H2O2) - induced toxicity in Caco-2 cells. Total phenolic contents, free radical scavenging activity, and reducing capacity of L. robustum were measured. The effects of L. robustum on the cell viability and antioxidant defense system were explored. The expression of nuclear factor E2 related factor 2 (Nrf2) and antioxidant genes: quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and glutamate cysteine ligase (GCL) were analyzed by western blot and qPCR. Pretreatment of L. robustum could significantly reduce H2O2-induced toxicity, decrease the level of reactive oxygen species (ROS) and malondialdehyde (MDA), and increase the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR). By activating the expression of Nrf2 and antioxidant genes (NQO1, HO-1, and GCL), L. robustum exerts cytoprotective effect in Caco-2 cells dealt with H2O2. Therefore, the well-established model of Caco-2 cells demonstrates that L. robustum may modulate the cytoprotective effect against the H2O2-induced oxidative stress through the Nrf2 signaling pathway.

Download Full-text

Nuclear factor erythroid 2-related factor 2 rescues the oxidative stress induced by di-N-butylphthalate in testicular Leydig cells

Human & Experimental Toxicology ◽

10.1177/0960327114530744 ◽

2014 ◽

Vol 34 (2) ◽

pp. 145-152 ◽

Cited By ~ 10

Author(s):

B Shen ◽

W Wang ◽

L Ding ◽

Y Sao ◽

Y Huang ◽

...

Keyword(s):

Oxidative Stress ◽

Leydig Cells ◽

Target Genes ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Quinone Oxidoreductase ◽

Antioxidant Genes ◽

Protein Levels

Aim: This study aimed to determine whether nuclear factor erythroid 2-related factor 2 antagonized the oxidative stress induced by di- N-butylphthalate (DBP) in testicular Leydig cells. Methods: Mouse TM3 testicular Leydig cells were treated with Nrf2 knockdown (KD) or overexpression in the presence and absence of DBP. Oxidative profiles were examined. Nrf2 target antioxidant genes were studied, and the effects of Nrf2 inducer sulphoraphane (SFN) were tested. Results: DBP induced intracellular oxidative stress to a similar extent with Nrf2 KD. Expression and protein levels of Nrf2 were increased together with its target genes, namely heme oxygenase 1, nicotinamide adenine dinucleotide phosphate quinone oxidoreductase 1 and peroxiredoxin 6, following DBP stimulation. Use of SFN not only restored the intracellular oxidative toxicity but also cell proliferation and testosterone secretion in response to DBP. Conclusion: Increased Nrf2 activity, for example, by SFN can effectively antagonize the oxidative stress in testicular Leydig cells caused by DBP.

Download Full-text

Thymoquinone Prevents Dopaminergic Neurodegeneration by Attenuating Oxidative Stress Via the Nrf2/ARE Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2020.615598 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jianjian Dong ◽

Xiaoming Zhang ◽

Shijing Wang ◽

Chenchen Xu ◽

Manli Gao ◽

...

Keyword(s):

Oxidative Stress ◽

Nuclear Translocation ◽

Nigella Sativa ◽

Drug Candidate ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Protective Effects ◽

Quinone Oxidoreductase ◽

Neuroprotective Effects ◽

Antioxidant Genes

Studies have indicated that oxidative stress plays a crucial role in the development of Parkinson’s disease (PD) and other neurodegenerative conditions. Research has also revealed that nuclear factor erythroid 2-related factor 2 (Nrf2) triggers the expression of antioxidant genes via a series of antioxidant response elements (AREs), thus preventing oxidative stress. Thymoquinone (TQ) is the bioactive component of Nigella sativa, a medicinal plant that exhibits antioxidant and neuroprotective effects. In the present study we examined whether TQ alleviates in vivo and in vitro neurodegeneration induced by 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by acting as an activator of the Nrf2/ARE cascade. We showed that TQ significantly reduced MPP+-mediated cell death and apoptosis. Moreover, TQ significantly elevated the nuclear translocation of Nrf2 and significantly increased the subsequent expression of antioxidative genes such as Heme oxygenase 1 (HO-1), quinone oxidoreductase (NQO1) and Glutathione-S-Transferase (GST). The application of siRNA to silence Nrf2 led to an abolishment in the protective effects of TQ. We also found that the intraperitoneal injection of TQ into a rodent model of PD ameliorated oxidative stress and effectively mitigated nigrostriatal dopaminergic degeneration by activating the Nrf2-ARE pathway. However, these effects were inhibited by the injection of a lentivirus wrapped Nrf2 siRNA (siNrf2). Collectively, these findings suggest that TQ alleviates progressive dopaminergic neuropathology by activating the Nrf2/ARE signaling cascade and by attenuating oxidative stress, thus demonstrating that TQ is a potential novel drug candidate for the treatment of PD.

Download Full-text

Mifepristone-inducible recombinant adenovirus attenuates paraquat-induced lung injury in rats

Human & Experimental Toxicology ◽

10.1177/0960327114532381 ◽

2014 ◽

Vol 34 (1) ◽

pp. 32-43 ◽

Cited By ~ 6

Author(s):

G-L Hong ◽

Q-Q Cai ◽

J-P Tan ◽

X-Z Jiang ◽

G-J Zhao ◽

...

Keyword(s):

Lung Injury ◽

Recombinant Adenovirus ◽

Antioxidant Response ◽

Nuclear Factor Κb ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Dependent Manner ◽

Nuclear Factor ◽

Quinone Oxidoreductase ◽

Protein Levels

Objective: To investigate the effects of overexpression of nuclear factor E2-related factor-2 (NRF2) on lung injury in rats exposed to paraquat (PQ) poisoning. Methods: A mifepristone (RU486)-inducible recombinant adenoviral vector carrying the human NRF2 gene (Ad-RUNRF2) was constructed and transfected via airway into the rats 7 days before the administration of RU486. Rats were orally challenged with PQ at 20 mg/kg 24 h after the injection of RU486. On days 0.5, 3 and 21 after PQ poisoning, the expressions of NRF2 and cytokines related to inflammation and oxidation in lung tissue were examined. Results: RU486 remarkably enhanced NRF2 mRNA and NRF2 protein levels in Ad-RUNRF2-transfected rats in a dose-dependent manner ( p < 0.01). PQ stimulated compensatory overexpression of NRF2, heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO-1) in lungs on days 0.5 and 3 after exposure ( p < 0.05), but depleted the expression of catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione (GSH), with an increased malondialdehyde (MDA) ( p < 0.05). However, pretreatment with Ad-RUNRF2 and RU486 strongly enhanced the expression levels of NRF2, HO-1, NQO-1, CAT and GSH-Px in the lungs of PQ intoxicated rats, with increased GSH and decreased MDA ( p < 0.05). Pretreatment with Ad-RUNRF2 and RU486 also strongly suppressed the PQ-induced activation of nuclear factor κB (NF-κB) and decreased the levels of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). In addition, Ad-RUNRF2 and RU486 induction significantly reduced PQ-induced pathological changes in lungs and attenuated lung oedema and protein leakage caused by PQ ( p < 0.05). Conclusion: RU486-induced overexpression of NRF2 in lungs transfected with Ad-RUNRF2 can ameliorate PQ-induced lung injury by the activation of the NRF2-antioxidant response element (ARE) pathway.

Download Full-text

Detoxication mechanisms of Radix Tripterygium wilfordii via compatibility with Herba Lysimachia christinae in S180-bearing mice by involving Nrf2

Bioscience Reports ◽

10.1042/bsr20180429 ◽

2018 ◽

Vol 38 (4) ◽

Cited By ~ 2

Author(s):

Jun-Ming Wang ◽

Hong Cai ◽

Jin-Hua Li ◽

Rong-Xing Chen ◽

Yue-Yue Zhang ◽

...

Keyword(s):

Elevated Serum ◽

Antioxidant Defenses ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Tripterygium Wilfordii ◽

Quinone Oxidoreductase ◽

Antioxidant Genes ◽

Tripterygium Wilfordii Hook F ◽

Tripterygium Wilfordii Hook ◽

Factor Α

The combined administration between Radix Tripterygium wilfordii Hook F (LGT) and Herba Lysimachia christinae Hance (JQC) belongs to mutual detoxication compatibility of seven emotions in traditional Chinese medicine (TCM) theory. However, until now, the compatibility detoxication mechanisms remain unknown. The present study was undertaken to observe detoxication mechanisms of LGT through compatibility with JQC in tumor-bearing mice by involving NF-E2-related factor 2 (Nrf2)-mediated antioxidant defenses. In addition, influence of compatibility on antitumor activity was also investigated here. Our results demonstrated that compatibility with JQC administration significantly reversed LGT-elevated serum alanine/aspartate transaminase (ALT/AST) levels and alleviated hepatocytes’ swelling or degeneration damage, and at the ratio 2/1 (LGT/JQC) produced the strongest detoxication effect. Besides, compatibility with JQC administration reversed not only LGT-elevated hepatic malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) but also the LGT lowered GSH, glutathione-s transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and interleukin (IL)-10 levels. Furthermore, compatibility with JQC administration significantly up-regulated protein expression of Nrf2 and mRNA expression of it regulated downstream antioxidant genes such as heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase-1 (NQO1), and glutamate cysteine ligase catalytic subunit (GCLC). In addition, compatibility with JQC further decreased LGT-decreased tumor weight and at the ratio 2/1 (LGT/JQC) also exerted the strongest synergistic effect. Collectively, through compatibility with JQC exerted detoxication effect on LGT-induced hepatotoxicity and the mechanisms could be at least partly attributed to up-regulation of Nrf2 and its downstream signals, thereby enhancing antioxidant defenses, and inhibiting lipid peroxidation, oxidative stress, and inflammation. Additionally, at the ratio 2/1 (LGT/JQC) exerted the strongest effects on both detoxication and synergism.

Download Full-text

Neuroprotective Effects and Mechanisms of Procyanidins In Vitro and In Vivo

Molecules ◽

10.3390/molecules26102963 ◽

2021 ◽

Vol 26 (10) ◽

pp. 2963

Author(s):

Juan Chen ◽

Yixuan Chen ◽

Yangfan Zheng ◽

Jiawen Zhao ◽

Huilin Yu ◽

...

Keyword(s):

Antioxidant Activities ◽

Antioxidant Response ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Quinone Oxidoreductase ◽

Neuroprotective Effects ◽

Glutamate Cysteine Ligase ◽

Pheochromocytoma Cells

This study evaluated the neuroprotective effects and mechanisms of procyanidins (PCs). In vitro, rat pheochromocytoma cells (PC12 cells) were exposed to PCs (1, 2 or 4 μg/mL) or N-Acetyl-L-cysteine (NAC) (20 μM) for 24 h, and then incubated with 200 μM of H2O2 for 24 h. Compared with H2O2 alone, PCs significantly increased antioxidant activities (e.g., glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT)), decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased nuclear factor-erythroid 2-related factor 2 (Nrf2) accumulation and increased the expression of quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1), glutamate-cysteine ligase modifier subunit (GCLM), and glutamate-cysteine ligase catalytic subunit (GCLC). In vivo, zebrafish larvae (AB strain) 3 days post-fertilization (dpf) were exposed to NAC (30 μM) or PCs (4, 8 or 16 μg/mL) in the absence or presence of 300 μM of H2O2 for 4 days. Compared with H2O2 alone, PCs enhanced antioxidant activities (e.g., GSH-Px, CAT, and SOD), decreased levels of ROS and MDA, and enhanced Nrf2/ antioxidant response element (ARE) activation and raised expression levels of NQO1, HO-1, GCLM, and GCLC. In conclusion, these results indicated that PCs exerted neuroprotective effects via activating the Nrf2/ARE pathway and alleviating oxidative damage.

Download Full-text

Oroxylin A exerts anti-inflammatory activity on lipopolysaccharide-induced mouse macrophage via Nrf2/ARE activation

Biochemistry and Cell Biology ◽

10.1139/bcb-2014-0030 ◽

2014 ◽

Vol 92 (5) ◽

pp. 337-348 ◽

Cited By ~ 31

Author(s):

Ming Ye ◽

Qing Wang ◽

Weifeng Zhang ◽

Zhiyu Li ◽

Yajing Wang ◽

...

Keyword(s):

Protein Expression ◽

Inflammatory Diseases ◽

Antioxidant Response ◽

Raw264.7 Cells ◽

Luciferase Reporter ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Oroxylin A ◽

Quinone Oxidoreductase ◽

Cox 2

Regulating inflammation could be an important measure for the effective treatment of cancer. Here we examine the mechanisms by which oroxylin A inhibits inflammation in RAW264.7 cells. The results demonstrate that pretreatment with oroxylin A (50, 100, and 150 μmol/L) inhibited lipopolysaccharide (LPS)-induced mRNA and protein expression of COX-2 and iNOS. In addition, oroxylin A significantly increased the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and NADP(H):quinone oxidoreductase (NQO1), induced Nrf2 translocation to the nucleus and up-regulated antioxidant response element (ARE)-luciferase reporter activity. Moreover, oroxylin A inhibited Nrf2 ubiquitination and proteasome activity. Transfection with Nrf2 siRNA knocked down Nrf2 expression and partially reversed oroxylin A-mediated inhibition of LPS-induced COX-2 and iNOS expression. Importantly, we showed for the first time that Nrf2 plays an important role in oroxylin A-suppressed inflammation in RAW264.7 cells. Uncovering the effect of oroxylin A on the regulation of Nrf2 signaling may be beneficial for developing new therapeutic strategies against inflammatory diseases.

Download Full-text

Heme-Mediated Activation of the Nrf2/HO-1 Axis Attenuates Calcification of Valve Interstitial Cells

Biomedicines ◽

10.3390/biomedicines9040427 ◽

2021 ◽

Vol 9 (4) ◽

pp. 427

Author(s):

Enikő Balogh ◽

Arpan Chowdhury ◽

Haneen Ababneh ◽

Dávid Máté Csiki ◽

Andrea Tóth ◽

...

Keyword(s):

Target Gene ◽

Interstitial Cells ◽

Protective Role ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Valvular Interstitial Cells ◽

Aortic Valves ◽

Antioxidant Genes ◽

Valve Interstitial Cells ◽

Nrf2 Target Gene

Calcific aortic valve stenosis (CAVS) is a heart disease characterized by the progressive fibro-calcific remodeling of the aortic valves, an actively regulated process with the involvement of the reactive oxygen species-mediated differentiation of valvular interstitial cells (VICs) into osteoblast-like cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of a variety of antioxidant genes, and plays a protective role in valve calcification. Heme oxygenase-1 (HO-1), an Nrf2-target gene, is upregulated in human calcified aortic valves. Therefore, we investigated the effect of Nrf2/HO-1 axis in VIC calcification. We induced osteogenic differentiation of human VICs with elevated phosphate and calcium-containing osteogenic medium (OM) in the presence of heme. Heme inhibited Ca deposition and OM-induced increase in alkaline phosphatase and osteocalcin (OCN) expression. Heme induced Nrf2 and HO-1 expression in VICs. Heme lost its anti-calcification potential when we blocked transcriptional activity Nrf2 or enzyme activity of HO-1. The heme catabolism products bilirubin, carbon monoxide, and iron, and also ferritin inhibited OM-induced Ca deposition and OCN expression in VICs. This study suggests that heme-mediated activation of the Nrf2/HO-1 pathway inhibits the calcification of VICs. The anti-calcification effect of heme is attributed to the end products of HO-1-catalyzed heme degradation and ferritin.

Download Full-text

Bisphenol A Modulates Autophagy and Exacerbates Chronic Kidney Damage in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22137189 ◽

2021 ◽

Vol 22 (13) ◽

pp. 7189

Author(s):

Alberto Ruiz Priego ◽

Emilio González Parra ◽

Sebastián Mas ◽

José Luis Morgado-Pascual ◽

Marta Ruiz-Ortega ◽

...

Keyword(s):

Bisphenol A ◽

Hepatitis A Virus ◽

Antioxidant Response ◽

Heme Oxygenase 1 ◽

Tubular Damage ◽

Related Factor ◽

Related Gene ◽

Inflammatory Infiltration ◽

Proximal Tubular Epithelial Cells

BACKGROUND: Bisphenol A (BPA) is a ubiquitous environmental toxin that accumulates in chronic kidney disease (CKD). Our aim was to explore the effect of chronic exposition of BPA in healthy and injured kidney investigating potential mechanisms involved. METHODS: In C57Bl/6 mice, administration of BPA (120 mg/kg/day, i.p for 5 days/week) was done for 2 and 5 weeks. To study BPA effect on CKD, a model of subtotal nephrectomy (SNX) combined with BPA administration for 5 weeks was employed. In vitro studies were done in human proximal tubular epithelial cells (HK-2 line). RESULTS: Chronic BPA administration to healthy mice induces inflammatory infiltration in the kidney, tubular injury and renal fibrosis (assessed by increased collagen deposition). Moreover, in SNX mice BPA exposure exacerbates renal lesions, including overexpression of the tubular damage biomarker Hepatitis A virus cellular receptor 1 (Havcr-1/KIM-1). BPA upregulated several proinflammatory genes and increased the antioxidant response [Nuclear factor erythroid 2-related factor 2 (Nrf2), Heme Oxygenase-1 (Ho-1) and NAD(P)H dehydrogenase quinone 1 (Nqo-1)] both in healthy and SNX mice. The autophagy process was modulated by BPA, through elevated autophagy-related gene 5 (Atg5), autophagy-related gene 7 (Atg7), Microtubule-associated proteins 1A/1B light chain 3B (Map1lc3b/Lc3b) and Beclin-1 gene levels and blockaded the autophagosome maturation and flux (p62 levels). This autophagy deregulation was confirmed in vitro. CONCLUSIONS: BPA deregulates autophagy flux and redox protective mechanisms, suggesting a potential mechanism of BPA deleterious effects in the kidney.

Download Full-text