Source of early reactive oxygen species in the apoptosis induced by transforming growth factor-β in fetal rat hepatocytes

Herrera, Blanca; Murillo, Miguel; Álvarez-Barrientos, Alberto; Beltrán, Jesús; Fernández, Margarita; Fabregat, Isabel

doi:10.1016/j.freeradbiomed.2003.09.020

Cited by 128 publications

(116 citation statements)

References 47 publications

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“…The mechanism(s) through which Smad3 interacts with NADPH-like oxidase remain unknown, but previous work has demonstrated that Smad2/3, NADPH-oxidase, and ERK1/2 may interact to alter ROS [22]. These findings are also supported by previous work that demonstrates the rule of the NADPHlike oxidase system in hepatocyte ROS generation [20]. Furthermore, in TGFβ-mediated apoptosis, ROS generation in L1210 leukemic cells occurs at 60 minutes, similar to our findings in primary murine hepatocytes [23].…”

Section: Discussionsupporting

confidence: 61%

“…In order to investigate whether a NADPH-like system is involved in Smad3-dependent ROS increase after TGFβ treatment, ROS formation was fluorometrically evaluated in the presence and absence of 1 μM of diphenyleneiodonium chloride (DPI), a flavoprotein inhibitor of NADPH oxidase [20]. Pretreatment of hepatocytes with DPI prevented TGFβ-induced ROS increase, suggesting that this system is required for TGFβ-induced ROS generation (Fig.…”

Section: Role Of Ros In Tgfβ-mediated Apoptosismentioning

confidence: 99%

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Transforming growth factor beta mediates hepatocyte apoptosis through Smad3 generation of reactive oxygen species

et al. 2007

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TGFβ induces hepatocyte apoptosis via reactive oxygen species (ROS) generation, the mitochondrial permeability transition (MPT), and caspase activation. The role of the Smad pathway in these events is unknown. In this study primary hepatocytes were isolated from Smad3 wild-type (+/+) and knockout (−/−) mice, and were treated with TGFβ (5 ng/ml) and/or trolox (2 mM). ROS generation, MPT, TGFβ-dependent transcription, and apoptosis were assessed in the presence or absence of Smad3 wild-type (WT) and dominant-negative (DN) plasmids. With TGFβ treatment, Smad3 (−/−) hepatocytes did not generate ROS activity, exhibit MPT, activate caspases, or undergo apoptosis when compared to Smad 3 (+/+) hepatocytes. Similarly, transfection of Smad3 (+/+) hepatocytes with DN-Smad3 inhibited TGFβ-mediated transcription, ROS generation, MPT, and apoptosis. However, Smad3 (−/−) cells transfected with WT-Smad3 and treated with TGFβ demonstrated increased transcriptional activity, the MPT, and TGFβ-induced apoptosis. TGFβ-mediated ROS generation occurred through an NADPH-like oxidase pathway since diphenyleneiodonium chloride inhibited ROS induction. In conclusion, TGFβ-induced hepatocyte apoptosis occurs through Smad3 dependent activation of ROS with subsequent activation of the MPT and caspases.

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Section: Discussionsupporting

confidence: 61%

Section: Role Of Ros In Tgfβ-mediated Apoptosismentioning

confidence: 99%

Transforming growth factor beta mediates hepatocyte apoptosis through Smad3 generation of reactive oxygen species

et al. 2007

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“…In contrast, Prdx6 þ / þ LECs were resistant to identical oxidative stress, demonstrating an antioxidant role of PRDX6. Various reports show that higher levels of ROS are a common signal in different cell death pathways, and indicate a complex relationship between ROS levels and cell death, [48][49][50] in view of the finding that PRDX6-depleted cells bear higher levels of ROS, and are thereby more susceptible to oxidative stress.…”

Section: Phenotypic Changes In Prdx6 à/à Lecs Resemble Tgfb-induced Cmentioning

confidence: 99%

“…Recent reports have demonstrated that TGFb increases ROS by rapid downregulation of antioxidant genes. [35][36][37][38] Evidence shows that overexpression of PRDX6 reduces ROS generated in response to growth factors. 39,40 To determine the potential role of PRDX6 in reducing oxidative stress and acting as an antioxidant defense in vitro and in vivo, we utilized Prdx6 knockout mice.…”

Section: Introductionmentioning

confidence: 99%

Impaired homeostasis and phenotypic abnormalities in Prdx6−/−mice lens epithelial cells by reactive oxygen species: increased expression and activation of TGFβ

et al. 2005

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PRDX6, a member of the peroxiredoxins (PRDXs) family, is a key player in the removal of reactive oxygen species (ROS). Using targeted inactivation of the Prdx6 gene, we present evidence that the corresponding protein offsets the deleterious effects of ROS on lens epithelial cells (LECs) and regulates gene expression by limiting its levels. PRDX6-depleted LECs displayed phenotypic alterations and elevated a-smooth muscle actin and big-h3 expression (markers for cataractogenesis), indistinguishable from transforming growth factor b (TGFb)-induced changes. Biochemical assays disclosed enhanced levels of ROS, as well as high expression and activation of TGFb1 in Prdx6 À/À LECs. A CAT assay revealed transcriptional repression of lens epithelium-derived growth factor (LEDGF), HSP27, and aB-crystallin promoter activities in these cells. A gel mobility shift assay demonstrated the attenuation of LEDGF binding to heat shock or stress response elements present in these genes. A supply of PRDX6 toPrdx6 À/À LECs reversed these changes. Based on the above data, we propose a rheostat role for PRDX6 in regulating gene expression by controlling the ROS level to maintain cellular homeostasis.

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“…Briefly, the specimens were washed twice in PBS 1X, equilibrated with the equilibration buffer at room temperature for 10 seconds and incubated in a dark moist chamber at 37°C, for 1 h, with the Terminal Desoxynucleotidyl Transferase (TdT) solution in order to allow DNA elongation [48][49][50][51][52][53].…”

Section: Measurement Of Dna Fragmentationmentioning

confidence: 99%

Effect of Seminal Transforming Growth Factorß1 (TGFß1) and Glutathione on Apoptosis in Spermatozoa from Tunisian Infertile Men

Ben Ali

2017

Andrology

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We aimed to compare the effect of TGFB1 and glutathione on sperm necrosis in three groups of patients with increased necrospermia. The study included 120 men aged 37.6 ± 4.6 years consulting for sterility of the couple. Patients were subdivided into three groups according to the percentage of necrotic spermatozoa: necrospermia<30%; N=40), moderate necrozoospermia (50-80%, n=45) and severe necrozoospermia (>80%) For each patient, the sperm parameters were evaluated according to WHO standards, TGFB1 and glutathione Oxidized and reduced was carried out by the ELISA technique and by spectrophotometry respectively. We found a significant increase in the levels of TGFβ1 and DFI in moderate and severe necrospermia groups and positive correlations between these two factors and sperm parameters (numeration, mobility and morphology). In addition, a significant decrease in seminal GHSt was observed in the necrozoospermic groups compared to the control group. A strong correlation was observed between the degree of necrozoospermia and the fragmentation of sperm DNA (r=0.878, p=0.001). In addition, a significant positive correlation between TGFβ1 and DFI in the two groups of patients with moderate necrospermia (r=0.43, p<0.05) and severe necrospermia (r=0.52, p<0.05). This confirms that seminal TGFβ1 is a factor in the fragmentation of spermatozoa DNA. These results suggest that decreased glutathione and increased seminal TGFβ1 are important risk factors that can lead to a succession of morphological and functional alterations of spermatozoa resulting in necrozoospermia. Their perturbation in seminal plasma can lead to mediocre results of medically assisted procreation.

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Source of early reactive oxygen species in the apoptosis induced by transforming growth factor-β in fetal rat hepatocytes

Cited by 128 publications

References 47 publications

Transforming growth factor beta mediates hepatocyte apoptosis through Smad3 generation of reactive oxygen species

Transforming growth factor beta mediates hepatocyte apoptosis through Smad3 generation of reactive oxygen species

Impaired homeostasis and phenotypic abnormalities in Prdx6−/−mice lens epithelial cells by reactive oxygen species: increased expression and activation of TGFβ

Effect of Seminal Transforming Growth Factorß1 (TGFß1) and Glutathione on Apoptosis in Spermatozoa from Tunisian Infertile Men

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