TGF-β1 Triggers Oxidative Modifications and Enhances Apoptosis in Hit Cells Through Accumulation of Reactive Oxygen Species by Suppression of Catalase and Glutathione Peroxidase

Our previous studies have indicated that transforming growth factor (TGF)-β1 and VEGF expression are increased in the smooth muscle cell (SMC) layer of the pulmonary vessels of lambs with pulmonary hypertension secondary to increased pulmonary blood flow. Furthermore, we found that TGF-β1 expression increased before VEGF. Because of the increased blood flow in the shunt lambs, the SMC in the pulmonary vessels are exposed to increased levels of the mechanical force, cyclic stretch. Thus, in this study, using primary cultures of pulmonary arterial SMC isolated from pulmonary arteries of 4-wk-old lambs, we investigated the role of cyclic stretch in the apparent coordinated regulation of TGF-β1 and VEGF. Our results demonstrated that cyclic stretch induced a significant increase in VEGF expression both at the mRNA and protein levels ( P < 0.05). The increased VEGF mRNA was preceded by both an increased expression and secretion of TGF-β1 and an increase in reactive oxygen species (ROS) generation. In addition, a neutralizing antibody against TGF-β1 abolished the cyclic stretch-dependent increases in both superoxide generation and VEGF expression. Our data also demonstrated that cyclic stretch activated an NAD(P)H oxidase that was TGF-β1 dependent and that NAD(P)H oxidase inhibitors abolished the cyclic stretch-dependent increase in VEGF expression. Therefore, our results indicate that cyclic stretch upregulates VEGF expression via the TGF-β1-dependent activation of NAD(P)H oxidase and increased generation of ROS.

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Modulation of Intracellular Reactive Oxygen Species Level in Chondrocytes by IGF-1, FGF, and TGF-β1

Connective Tissue Research ◽

10.1080/03008200701331516 ◽

2007 ◽

Vol 48 (3) ◽

pp. 149-158 ◽

Cited By ~ 25

Author(s):

Navid Jallali ◽

Hyder Ridha ◽

Christopher Thrasivoulou ◽

Peter Butler ◽

Timothy Cowen

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Intracellular Reactive Oxygen Species ◽

Species Level ◽

Reactive Oxygen Species Level ◽

Oxygen Species ◽

Tgf Β1

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Salvianolic Acid A Protects Against Oxidative Stress and Apoptosis Induced by Intestinal Ischemia-Reperfusion Injury Through Activation of Nrf2/HO-1 Pathways

Cellular Physiology and Biochemistry ◽

10.1159/000493833 ◽

2018 ◽

Vol 49 (6) ◽

pp. 2320-2332 ◽

Cited By ~ 18

Author(s):

Guo Zu ◽

Tingting Zhou ◽

Ningwei Che ◽

Xiangwen Zhang

Keyword(s):

Reactive Oxygen Species ◽

Glutathione Peroxidase ◽

Ischemia Reperfusion ◽

Reactive Oxygen ◽

Oxygen Species ◽

Salvianolic Acid ◽

Salvianolic Acid A ◽

Tnf Α

Background/Aims: Ischemia-reperfusion (I/R) adversely affects the intestinal mucosa. The major mechanisms of I/R are the generation of reactive oxygen species (ROS) and apoptosis. Salvianolic acid A (SalA) is suggested to be an effective antioxidative and antiapoptotic agent in numerous pathological injuries. The present study investigated the protective role of SalA in I/R of the intestine. Methods: Adult male Sprague-Dawley rats were subjected to intestinal I/R injury in vivo. In vitro experiments were performed in IEC-6 cells subjected to hypoxia/ reoxygenation (H/R) stimulation to simulate intestinal I/R. TNF-α, IL-1β, and IL-6 levels were measured using enzyme-linked immunosorbent assay. Malondialdehyde and myeloperoxidase and glutathione peroxidase levels were measured using biochemical analysis. Apoptosis was measured by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling staining or flow cytometry in vivo and in vitro. The level of reactive oxygen species (ROS) was measured by dichlorodihydrofluorescin diacetate (DCFH-DA) staining. Western blotting was performed to determine the expression of heme oxygenase-1 (HO-1), Nrf2 and proteins associated with apoptosis. The mRNA expressions of Nrf2 and HO-1 were detected by quantitative real-time polymerase chain reaction in vivo and in vitro. Results: Malondialdehyde level and myeloperoxidase and glutathione peroxidase, TNF-α, IL-1β, and IL-6 levels group in intestinal tissue decreased significantly in the SalA pretreatment groups compared to the I/R group. SalA markedly abolished intestinal injury compared to the I/R group. SalA significantly attenuated apoptosis and increased Nrf2/HO-1 expression in vivo and in vitro. However, Nrf2 siRNA treatment partially abrogated the above mentioned effects of SalA in H/R-induced ROS and apoptosis in IEC-6 cells. Conclusion: The present study demonstrated that SalA ameliorated oxidation, inhibited the release of pro-inflammatory cytokines and alleviated apoptosis in I/R-induced injury and that these protective effects may partially occur via regulation of the Nrf2/ HO-1 pathways.

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184 Effects of cyanidin supplementation on invitro maturation of pig oocytes

Reproduction Fertility and Development ◽

10.1071/rdv32n2ab184 ◽

2020 ◽

Vol 32 (2) ◽

pp. 220

Author(s):

E. Hicks ◽

M. Mentler ◽

B. D. Whitaker

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Superoxide Dismutase ◽

Glutathione Peroxidase ◽

Oocyte Maturation ◽

Catalase Activity ◽

Reactive Oxygen ◽

Oxygen Species ◽

Enzyme Mechanisms ◽

Maturation Medium

Oxidative stress can have a negative effect on oocyte maturation during invitro production of pig embryos. Imbalance of reactive oxygen species and antioxidant levels can affect the progression of oocyte maturation up to the point of fertilization. Antioxidants are effective in maintaining more ideal reactive oxygen species levels, which help to protect oocytes from potential harmful effects of oxidative stress. Berries from the elder plant (Sambucus sp.) contain high levels of a broad spectrum of antioxidants. One of these antioxidants, cyanidin, when supplemented to maturation medium at 100μM concentrations, reduces reactive oxygen species formation and improves IVF and early embryonic development in pigs. However, changes in the enzyme mechanisms of action during oocyte maturation due to cyanidin supplementation are unknown. Therefore, the objective of this study was to characterise the intracellular oocyte enzyme mechanisms between oocytes supplemented with 100μM cyanidin during 40 to 44h of maturation (n=600) and oocytes without supplementation of cyanidin during maturation (n=558). At the end of maturation, oocytes were evaluated for either glutathione peroxidase (n=300), catalase (n=564), or superoxide dismutase (n=294) activities. Glutathione peroxidase activity was determined by following the rate of NADPH oxidation, catalase activity was determined by following the rate of hydrogen peroxide decomposition, and superoxide dismutase activity was determined by following the reduction rate of cytochrome c, utilising the xanthine-xanthine oxidase system. Data were analysed using ANOVA and Tukey's test. There were no significant differences between oocytes matured with 100μM cyanidin and those that were not when comparing glutathione peroxidase and superoxide dismutase activities. Supplementation of 100μM cyanidin to maturation medium increased (P<0.05) catalase activity in oocytes (0.78±0.15 units/oocyte) compared with no cyanidin supplementation (0.14±0.11 units/oocyte). These results indicate that supplementing 100μM cyanidin to the maturation medium of pig oocytes could reduce the negative effects of oxidative stress by increasing intracellular catalase activity during oocyte maturation.

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Front Cover: Redox Proteomic Analysis Reveals Oxidative Modifications of Proteins by Increased Levels of Intracellular Reactive Oxygen Species during Hypoxia Adaptation of Aspergillus fumigatus

PROTEOMICS ◽

10.1002/pmic.201970031 ◽

2019 ◽

Vol 19 (5) ◽

pp. 1970031

Author(s):

Elena Shekhova ◽

Lia Ivanova ◽

Thomas Krüger ◽

Maria C. Stroe ◽

Juliane Macheleidt ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Aspergillus Fumigatus ◽

Proteomic Analysis ◽

Reactive Oxygen ◽

Intracellular Reactive Oxygen Species ◽

Oxygen Species ◽

Front Cover ◽

Hypoxia Adaptation ◽

Oxidative Modifications

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Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling

Bioscience Reports ◽

10.1042/bsr20182293 ◽

2019 ◽

Vol 39 (4) ◽

Author(s):

Hong-Min Chen ◽

Jia-Jia Dai ◽

Rui Zhu ◽

Fang-Fang Peng ◽

Su-Zhen Wu ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Parathyroid Hormone ◽

Mesangial Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Related Protein ◽

Egfr Signaling ◽

Mesenchymal Transition ◽

Parathyroid Hormone Related Protein ◽

Tgf Β1

Abstract Parathyroid hormone-related protein (PTHrP) is known to be up-regulated in both glomeruli and tubules in patients with diabetic kidney disease (DKD), but its role remains unclear. Previous studies show that PTHrP-induced hypertrophic response in mesangial cells (MCs) and epithelial-mesenchymal transition (EMT) in tubuloepithelial cells can be mediated by TGF-β1. In the present study, although long-term PHTrP (1–34) treatment increased the mRNA and protein level of TGF-β1 in primary rat MCs, fibronectin up-regulation occurred earlier, suggesting that fibronectin induction is independent of TGF-β1/Smad signaling. We thus evaluated the involvement of epidermal growth factor receptor (EGFR) signaling and found that nicotinamide adenine dinucleotide phosphate oxidase-derived reactive oxygen species mediates PTHrP (1–34)-induced Src kinase activation. Src phosphorylates EGFR at tyrosine 845 and then transactive EGFR. Subsequent PI3K activation mediates Akt and ERK1/2 activation. Akt and ERK1/2 discretely lead to excessive protein synthesis of fibronectin. Our study thus demonstrates the new role of PTHrP in fibronectin up-regulation for the first time in glomerular MCs. These data also provided new insights to guide development of therapy for glomerular sclerosis.

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