scholarly journals TAZ as a novel regulator of oxidative damage in decidualization via Nrf2/ARE/Foxo1 pathway

2021 ◽  
Author(s):  
Hai-Fan Yu ◽  
Lian-Wen Zheng ◽  
Zhan-Qing Yang ◽  
Yu-Si Wang ◽  
Ting-Ting Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Oxidative Damage ◽  
Stromal Cell ◽  
Hippo Pathway ◽  
Mitochondrial Respiratory Chain ◽  
Antioxidant Response ◽  
Mtdna Copy Number ◽  
Respiratory Chain Complexes ◽  
Differentiation Markers ◽  
Intracellular Ros

AbstractTAZ, as a crucial effector of Hippo pathway, is required for spermatogenesis and fertilization, but little is known regarding its physiological function in uterine decidualization. In this study, we showed that TAZ was localized in the decidua, where it promoted stromal cell proliferation followed by accelerated G1/S phase transition via Ccnd3 and Cdk4 and induced the expression or activity of stromal differentiation markers Prl8a2, Prl3c1 and ALP, indicating the importance of TAZ in decidualization. Knockdown of TAZ impeded HB-EGF induction of stromal cell proliferation and differentiation. Under oxidative stress, TAZ protected stromal differentiation against oxidative damage by reducing intracellular ROS and enhancing cellular antioxidant capacity dependent on the Nrf2/ARE/Foxo1 pathway. TAZ strengthened the transcriptional activity of Nrf2 which directly bound to the antioxidant response element (ARE) of Foxo1 promoter region. Additionally, silencing TAZ caused accumulation of intracellular ROS through heightening NOX activity whose blockade by APO reversed the disruption in stromal differentiation. Further analysis revealed that TAZ might restore mitochondrial function, as indicated by the increase in ATP level, mtDNA copy number and mitochondrial membrane potential with the reduction in mitochondrial superoxide. Additionally, TAZ modulated the activities of mitochondrial respiratory chain complexes I and III whose suppression by ROT and AA resulted in the inability of TAZ to defend against oxidative damage to stromal differentiation. Moreover, TAZ prevented stromal cell apoptosis by upregulating Bcl2 expression and inhibiting Casp3 activity and Bax expression. In summary, TAZ might mediate HB-EGF function in uterine decidualization through Ccnd3 and ameliorate oxidative damage to stromal cell differentiation via Nrf2/ARE/Foxo1 pathway.

Impaired Activity of Mitochondrial Respiratory Chain Enzyme Complexes and Mitochondrial Genomic Aberrations in Leukemia Cells from Patients with Acute Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1918-1918
Author(s):  
Myung-Geun Shin ◽  
Hyeoung Joon Kim ◽  
Hye-Ran Kim ◽  
Il-Kwon Lee ◽  
Duck Cho ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Mitochondrial Respiratory Chain ◽  
Ros Generation ◽  
Mtdna Copy Number ◽  
Respiratory Chain Complexes ◽  
Respiratory Chain Enzyme ◽  
Control Subjects ◽  
Genomic Aberrations ◽  
Enzyme Complexes ◽  
Mitochondrial Respiratory

Abstract Background: Mitochondrial DNA (mtDNA) was particularly susceptible to oxidative damage and mutation because of the high rate of reactive oxygen species (ROS) generation and inefficient mtDNA repair system. Somatic mutations of mtDNA lead to errors in the mtDNA-encoded polypeptide chains belonging to the proton-translocating complexes of the mitochondrial inner membrane. Therefore, we investigated level of ROS, mitochondrial genomic aberrations (mitochondrial genomic instability, mtGI) and the change in enzyme activity of mitochondrial respiratory chain complexes I–IV and in acute myeloid leukemia (AML) cells. Methods: Forty-eight AML bone marrow samples and 57 control blood samples were used after receiving informed consent. The intracellular ROS generation of cells can be investigated using the 2′,7′-dichlorfl uorescein-diacetate and flow cytometry. The results were expressed as mean fluorescence intensity (MFI). We sequenced the mtDNA control region, the tRNA leucine 1 gene plus part of NADH dehydrogenase (ND) 1, and cytochrome b (CYTB) directly and checked the activity of mitochondrial respiratory chain enzyme complexes I to IV using a spectrophotometric kinetic assay. To investigate mtGI, we also examined six mtGI repeats (303 poly C, 16184 poly C, 514CA repeats, 3566 poly C, 12385 poly C and 12418 poly A) using size-based PCR product separation with capillary electrophoresis. mtGI was further confirmed by cloning and sequencing. The mtDNA molecules were analyzed quantitatively using real-time PCR. Results: MFI in AML cells (4,435±709) was significantly higher than those in control blood cells (1,562±141) (P<0.05). Many polymorphisms, as well as new mtDNA variants in the control region and ND1 and CYTB genes were detected in this study. A total of 606 mtDNA sequence variants were identified. Of these, 15 mtDNA variants were identified as novel mutations that were absent from control subjects and established mtDNA polymorphism databases. There were profound alterations of mtGI in the 303 poly C, 16184 poly C, and 514 CA repeats. Seven patients (15%) had leukemia cell-specific mtDNA substitution mutations in the ND1 and CYTB genes. The enzyme activities of AML cells compared with control subjects were 0.828±2.72 vs. −2.48±3.18 for complex I, 0.03±0.08 vs. 0.144±1.72 for complex II/III, and 0.244±0.16 vs. 0.505±0.73 for complex IV. The AML cells showed decreased enzyme activity in respiratory chain complexes I, II, and III. The AML cells had an approximately two-fold decrease in mtDNA copy number compared with the results for control subjects. Conclusion: Mitochondrial genomic aberrations were commonly observed in primary AML cells. High level of ROS in these cells might be an injury to the mitochondrial genome. These mtDNA alterations may impair the activity of mitochondrial respiratory chain enzyme complexes and reduce the mtDNA copy number in patients with AML.

scholarly journals HB-EGF Ameliorates Oxidative Stress-Mediated Uterine Decidualization Damage

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Hai-Fan Yu ◽  
Cui-Cui Duan ◽  
Zhan-Qing Yang ◽  
Yu-Si Wang ◽  
Zhan-Peng Yue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Differentiation ◽  
Stromal Cell ◽  
Chain Complex ◽  
Mitochondrial Respiratory Chain ◽  
Mtdna Copy Number ◽  
Mitochondrial Respiratory Chain Complex ◽  
Mitochondrial Superoxide ◽  
Antioxidant Function ◽  
Uterine Stromal Cell

HB-EGF is essential for uterine decidualization, but its antioxidant function remains largely unclear. Here, we found that HB-EGF promoted the proliferation of stromal cells followed by the accelerated transition of the cell cycle from G1 to S phase and enhanced the expression or activity of Prl8a2, Prl3c1, and ALP which were well-established markers for uterine stromal cell differentiation during decidualization. Under oxidative stress, stromal cell differentiation was impaired, but this impairment was abrogated by rHB-EGF accompanied with the reduced levels of ROS and MDA which were regarded as the biomarkers for oxidative stress, indicating an antioxidant role of HB-EGF. Further analysis revealed that HB-EGF enhanced the activities of antioxidant enzymes SOD, CAT, and GPX, where addition of GPX inhibitor MS attenuated the induction of rHB-EGF on Prl8a2, Prl3c1, and ALP. Meanwhile, HB-EGF rescued the content of GSH and restored the ratio of GSH/GSSG after exposure to H2O2 but did not alter NOX activity. Along with a decline for mitochondrial superoxide, exogenous rHB-EGF improved the damage of oxidative stress on mtDNA copy number, ATP level, mitochondrial membrane potential, and activities of mitochondrial respiratory chain complex I and III whose blockage by ROT and AA led to a failure of rHB-EGF in protecting stromal cell differentiation against injury. Moreover, HB-EGF prevented stromal cell apoptosis by inhibiting Caspase-3 activity and Bax expression and recovering the level of Bcl-2 mRNA. Collectively, HB-EGF might ameliorate oxidative stress-mediated uterine decidualization damage.

scholarly journals 6-shogaol suppresses oxidative damage in L6 muscle cells

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Jinyoung Hur ◽  
Yeonmi Lee ◽  
Chang Jun Lee ◽  
Ho-Young Park ◽  
Sang Yoon Choi
Keyword(s):  
Skeletal Muscle ◽  
Essential Oil ◽  
Oxidative Damage ◽  
Zingiber Officinale ◽  
Muscle Cells ◽  
Skeletal Muscle Cell ◽  
Intracellular Ros ◽  
Zingiber Officinale Roscoe ◽  
Mrna And Protein Expression ◽  
L6 Muscle Cells

Abstract Ginger (Zingiber Officinale Roscoe) has been known reduce muscle pain after exercise, and 6-shogaol {(E)-1-(4-Hydroxy-3-methoxyphenyl)dec-4-en-3-one)} is the major essential oil contained in ginger. In this study, the protective effect of 6-shogaol on L6 muscle cells against oxidative damage was measured. 6-shagol inhibited the damage of L6 cell induced by H2O2, and allowed the increase in mRNA and protein expression levels of intracellular HO-1 and NRF2. 6-shogaol also reduced the production of intracellular ROS. These results suggested that 6-shagol effectively inhibits oxidative damage of skeletal muscle cell.

Effect of gonadotropins on human endometrial stromal cell proliferation in vitro

2002 ◽  
Vol 266 (4) ◽  
pp. 223-228 ◽  
Author(s):  
Seung Yup Ku ◽  
Y. M. Choi ◽  
Chang Suk Suh ◽  
Seok Hyun Kim ◽  
Jung Gu Kim ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stromal Cell ◽  
Endometrial Stromal Cell ◽  
Human Endometrial Stromal Cell ◽  
Proliferation In Vitro

scholarly journals Marine Compound 3-bromo-4,5-dihydroxybenzaldehyde Protects Skin Cells against Oxidative Damage via the Nrf2/HO-1 Pathway

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 234 ◽  
Author(s):  
Yea Seong Ryu ◽  
Pincha Devage Sameera Madushan Fernando ◽  
Kyoung Ah Kang ◽  
Mei Jing Piao ◽  
Ao Xuan Zhen ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Antioxidant Response ◽  
Signaling Cascades ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Skin Cells ◽  
Reverse Transcription Pcr ◽  
Extracellular Signal ◽  
Diphenyltetrazolium Bromide ◽  
Marine Compound

In this study, we aimed to illustrate the potential bio-effects of 3-bromo-4,5-dihydroxybenzaldehyde (3-BDB) on the antioxidant/cytoprotective enzyme heme oxygenase-1 (HO-1) in keratinocytes. The antioxidant effects of 3-BDB were examined via reverse transcription PCR, Western blotting, HO-1 activity assay, and immunocytochemistry. Chromatin immunoprecipitation analysis was performed to test for nuclear factor erythroid 2-related factor 2 (Nrf2) binding to the antioxidant response element of the HO-1 promoter. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the cytoprotective effects of 3-BDB were mediated by the activation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB, Akt) signaling. Moreover, 3-BDB induced the phosphorylation of ERK and Akt, while inhibitors of ERK and Akt abrogated the 3-BDB-enhanced levels of HO-1 and Nrf2. Finally, 3-BDB protected cells from H2O2- and UVB-induced oxidative damage. This 3-BDB-mediated cytoprotection was suppressed by inhibitors of HO-1, ERK, and Akt. The present results indicate that 3-BDB activated Nrf2 signaling cascades in keratinocytes, which was mediated by ERK and Akt, upregulated HO-1, and induced cytoprotective effects against oxidative stress.

scholarly journals Protein Kinase A/CREB Signaling Prevents Adriamycin-Induced Podocyte Apoptosis via Upregulation of Mitochondrial Respiratory Chain Complexes

2017 ◽  
Vol 38 (1) ◽  
Author(s):  
Kewei Xie ◽  
Mingli Zhu ◽  
Peng Xiang ◽  
Xiaohuan Chen ◽  
Ayijiaken Kasimumali ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Respiratory Chain ◽  
Mitochondrial Respiratory Chain ◽  
Peroxisome Proliferator ◽  
Respiratory Chain Complexes ◽  
Peroxisome Proliferator Activated Receptor ◽  
Kinase A ◽  
Mitochondrial Respiratory

ABSTRACT Previous work showed that the activation of protein kinase A (PKA) signaling promoted mitochondrial fusion and prevented podocyte apoptosis. The cAMP response element binding protein (CREB) is the main downstream transcription factor of PKA signaling. Here we show that the PKA agonist 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate–cyclic AMP (pCPT-cAMP) prevented the production of adriamycin (ADR)-induced reactive oxygen species and apoptosis in podocytes, which were inhibited by CREB RNA interference (RNAi). The activation of PKA enhanced mitochondrial function and prevented the ADR-induced decrease of mitochondrial respiratory chain complex I subunits, NADH-ubiquinone oxidoreductase complex (ND) 1/3/4 genes, and protein expression. Inhibition of CREB expression alleviated pCPT-cAMP-induced ND3, but not the recovery of ND1/4 protein, in ADR-treated podocytes. In addition, CREB RNAi blocked the pCPT-cAMP-induced increase in ATP and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1-α). The chromatin immunoprecipitation assay showed enrichment of CREB on PGC1-α and ND3 promoters, suggesting that these promoters are CREB targets. In vivo, both an endogenous cAMP activator (isoproterenol) and pCPT-cAMP decreased the albumin/creatinine ratio in mice with ADR nephropathy, reduced glomerular oxidative stress, and retained Wilm's tumor suppressor gene 1 (WT-1)-positive cells in glomeruli. We conclude that the upregulation of mitochondrial respiratory chain proteins played a partial role in the protection of PKA/CREB signaling.

scholarly journals NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway

2011 ◽  
Vol 193 (4) ◽  
pp. 633-642 ◽  
Author(s):  
Sandra Habbig ◽  
Malte P. Bartram ◽  
Roman U. Müller ◽  
Ricarda Schwarz ◽  
Nikolaos Andriopoulos ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Nuclear Translocation ◽  
Hippo Pathway ◽  
Negative Regulator ◽  
Hippo Signaling ◽  
Transcriptional Coactivator ◽  
Hippo Signaling Pathway ◽  
The Hippo Pathway ◽  
Potent Negative Regulator

The conserved Hippo signaling pathway regulates organ size in Drosophila melanogaster and mammals and has an essential role in tumor suppression and the control of cell proliferation. Recent studies identified activators of Hippo signaling, but antagonists of the pathway have remained largely elusive. In this paper, we show that NPHP4, a known cilia-associated protein that is mutated in the severe degenerative renal disease nephronophthisis, acts as a potent negative regulator of mammalian Hippo signaling. NPHP4 directly interacted with the kinase Lats1 and inhibited Lats1-mediated phosphorylation of the Yes-associated protein (YAP) and TAZ (transcriptional coactivator with PDZ-binding domain), leading to derepression of these protooncogenic transcriptional regulators. Moreover, NPHP4 induced release from 14-3-3 binding and nuclear translocation of YAP and TAZ, promoting TEA domain (TEAD)/TAZ/YAP-dependent transcriptional activity. Consistent with these data, knockdown of NPHP4 negatively affected cellular proliferation and TEAD/TAZ activity, essentially phenocopying loss of TAZ function. These data identify NPHP4 as a negative regulator of the Hippo pathway and suggest that NPHP4 regulates cell proliferation through its effects on Hippo signaling.

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