scholarly journals HIF1A-dependent increase in endothelin 2 levels in granulosa cells: role of hypoxia, LH/cAMP, and reactive oxygen species

Reproduction ◽  
2015 ◽  
Vol 149 (1) ◽  
pp. 11-20 ◽  
Author(s):  
Ronit Yalu ◽  
Adepeju Esther Oyesiji ◽  
Iris Eisenberg ◽  
Tal Imbar ◽  
Rina Meidan
Keyword(s):  
Reactive Oxygen Species ◽  
Mrna Expression ◽  
Granulosa Cells ◽  
Time Window ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Protein Levels ◽  
Concomitant Reduction

Hypoxia-inducible factor 1 alpha (HIF1A) and endothelin 2 (EDN2) are transiently expressed during the same time window in the developing corpus luteum (CL). In this study, we sought to investigate the involvement of LH/cAMP, reactive oxygen species (ROS), and a hypoxia-mimetic compound (CoCl2) on HIF1A expression and how it affected EDN2 levels, using transformed human granulosa cells (thGCs) and primary bovine granulosa cells (GCs). CoCl2 elevated HIF1A protein levels in thGCs in a dose-dependent manner. Forskolin alone had no significant effect; however, forskolin and CoCl2 together further induced HIF1A protein and EDN2 mRNA expression in thGCs. Similarly, in primary GCs, LH with CoCl2 synergistically augmented HIF1A protein levels, which resulted in higher expression of EDN2 and another well-known hypoxia-inducible gene, VEGF (VEGFA). Importantly, LH alone elevated HIF1A mRNA but not its protein. The successful knockdown of HIF1A in thGCs using siRNA abolished hypoxia-induced EDN2 and also the additive effect of forskolin and CoCl2. We then examined the roles of ROS in thGCs: hydrogen peroxide (20 and 50 μM) elevated HIF1A protein as well as the expression of EDN2, implying that induction of HIF1A protein levels is sufficient to stimulate the expression of EDN2 (and VEGF) in normoxia. A broad-range ROS scavenger, butylated hydroxyanisole, inhibited CoCl2-induced HIF1A protein with a concomitant reduction in the mRNA expression of EDN2 and VEGF in thGCs. The results obtained in this study suggest that HIF1A, induced by various stimuli, is an essential mediator of EDN2 mRNA expression. The results may also explain the rise in the levels of HIF1A-dependent genes (EDN2 and VEGF) in the developing CL.

scholarly journals Blockage of Potassium Channel Inhibits Proliferation of Glioma Cells Via Increasing Reactive Oxygen Species

2014 ◽  
Vol 22 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Li Hu ◽  
Li-Li Li ◽  
Zhi-Guo Lin ◽  
Zhi-Chao Jiang ◽  
Hong-Xing Li ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Brain Glioma ◽  
Protein Levels ◽  
Glioma Cell Proliferation

The potassium (K+) channel plays an important role in the cell cycle and proliferation of tumor cells, while its role in brain glioma cells and the signaling pathways remains unclear. We used tetraethylammonium (TEA), a nonselective antagonist of big conductance K+ channels, to block K+ channels in glioma cells, and antioxidant N-acetyl-l-cysteine (NAC) to inhibit production of intracellular reactive oxygen species (ROS). TEA showed an antiproliferation effect on C6 and U87 glioma cells in a time-dependent manner, which was accompanied by an increased intracellular ROS level. Antioxidant NAC pretreatment reversed TEA-mediated antiproliferation and restored ROS level. TEA treatment also caused significant increases in mRNA and protein levels of tumor-suppressor proteins p53 and p21, and the upregulation was attenuated by pretreatment of NAC. Our results suggest that K+ channel activity significantly contributes to brain glioma cell proliferation via increasing ROS, and it might be an upstream factor triggering the activation of the p53/p21Cip1-dependent signaling pathway, consequently leading to glioma cell cycle arrest.

scholarly journals Cigarette Smoke Extract Activates Hypoxia-Inducible Factors in a Reactive Oxygen Species-Dependent Manner in Stroma Cells from Human Endometrium

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 48
Author(s):  
Naoko Kida ◽  
Yoshiyuki Matsuo ◽  
Yoshiko Hashimoto ◽  
Kenichiro Nishi ◽  
Tomoko Tsuzuki-Nakao ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Stromal Cells ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen ◽  
Protein Stabilization ◽  
Human Endometrium ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Endometrial Stromal Cells ◽  
Hypoxic Conditions

Cigarette smoking (CS) is a major contributing factor in the development of a large number of fatal and debilitating disorders, including degenerative diseases and cancers. Smoking and passive smoking also affect the establishment and maintenance of pregnancy. However, to the best of our knowledge, the effects of smoking on the human endometrium remain poorly understood. In this study, we investigated the regulatory mechanism underlying CS-induced hypoxia-inducible factor (HIF)-1α activation using primary human endometrial stromal cells and an immortalized cell line (KC02-44D). We found that the CS extract (CSE) increased reactive oxygen species levels and stimulated HIF-1α protein stabilization in endometrial stromal cells, and that CS-induced HIF-1α-dependent gene expression under non-hypoxic conditions in a concentration- and time-dependent manner. Additionally, we revealed the upregulated expression of a hypoxia-induced gene set following the CSE treatment, even under normoxic conditions. These results indicated that HIF-1α might play an important role in CS-exposure-induced cellular stress, inflammation, and endometrial remodeling.

scholarly journals Reactive Oxygen Species-Mediated Autophagy by Ursolic Acid Inhibits Growth and Metastasis of Esophageal Cancer Cells

2020 ◽  
Vol 21 (24) ◽  
pp. 9409
Author(s):  
Na-Ri Lee ◽  
Ruo Yu Meng ◽  
So-Young Rah ◽  
Hua Jin ◽  
Navin Ray ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Viability ◽  
Ursolic Acid ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Cell Viability Assay ◽  
Protein Levels ◽  
Lc3 Puncta ◽  
Dose Dependent

Ursolic acid (UA) possesses various pharmacological activities, such as antitumorigenic and anti-inflammatory effects. In the present study, we investigated the mechanisms underlying the effects of UA against esophageal squamous cell carcinoma (ESCC) (TE-8 cells and TE-12 cells). The cell viability assay showed that UA decreased the viability of ESCC in a dose-dependent manner. In the soft agar colony formation assay, the colony numbers and size were reduced in a dose-dependent manner after UA treatment. UA caused the accumulation of vacuoles and LC3 puncta, a marker of autophagosome, in a dose-dependent manner. Autophagy induction was confirmed by measuring the expression levels of LC3 and p62 protein in ESCC cells. UA increased LC3-II protein levels and decreased p62 levels in ESCC cells. When autophagy was hampered using 3-methyladenine (3-MA), the effect of UA on cell viability was reversed. UA also significantly inhibited protein kinase B (Akt) activation and increased p-Akt expression in a dose-dependent manner in ESCC cells. Accumulated LC3 puncta by UA was reversed after wortmannin treatment. LC3-II protein levels were also decreased after treatment with Akt inhibitor and wortmannin. Moreover, UA treatment increased cellular reactive oxygen species (ROS) levels in ESCC in a time- and dose-dependent manner. Diphenyleneiodonium (an ROS production inhibitor) blocked the ROS and UA induced accumulation of LC3-II levels in ESCC cells, suggesting that UA-induced cell death and autophagy are mediated by ROS. Therefore, our data indicate that UA inhibits the growth of ESCC cells by inducing ROS-dependent autophagy.

Hypoxic but not anoxic stabilization of HIF-1α requires mitochondrial reactive oxygen species

2002 ◽  
Vol 283 (5) ◽  
pp. L922-L931 ◽  
Author(s):  
Clara Schroedl ◽  
David S. McClintock ◽  
G. R. Scott Budinger ◽  
Navdeep S. Chandel
Keyword(s):  
Reactive Oxygen Species ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
A549 Cells ◽  
Reactive Oxygen ◽  
Protein Stabilization ◽  
Oxygen Species ◽  
Protein Levels ◽  
Transport Chain ◽  
Ht1080 Cells

The molecular mechanisms by which cells detect hypoxia (1.5% O2), resulting in the stabilization of hypoxia-inducible factor 1α (HIF-1α) protein remain unclear. One model proposes that mitochondrial generation of reactive oxygen species is required to stabilize HIF-1α protein. Primary evidence for this model comes from the observation that cells treated with complex I inhibitors, such as rotenone, or cells that lack mitochondrial DNA (ρ0-cells) fail to generate reactive oxygen species or stabilize HIF-1α protein in response to hypoxia. In the present study, we investigated the role of mitochondria in regulating HIF-1α protein stabilization under anoxia (0% O2). Wild-type A549 and HT1080 cells stabilized HIF-1α protein in response to hypoxia and anoxia. The ρ0-A549 cells and ρ0-HT1080 cells failed to accumulate HIF-1α protein in response to hypoxia. However, both ρ0-A549 and ρ0-HT1080 were able to stabilize HIF-1α protein levels in response to anoxia. Rotenone inhibited hypoxic, but not anoxic, stabilization of HIF-1α protein. These results indicate that a functional electron transport chain is required for hypoxic but not anoxic stabilization of HIF-1α protein.

Protective Effects of Crataegus pinnatifida Extracts and Crataegolic Acid Against Neurotoxicity of Paraquat in PC12 Cells

2021 ◽  
Vol 20 (1) ◽  
pp. 76-83
Author(s):  
Chi-Sen Chang ◽  
Yuh-Chiang Shen ◽  
Chi-Wen Juan ◽  
Chia-Lin Chang ◽  
Po-Kai Lin
Keyword(s):  
Reactive Oxygen Species ◽  
Pc12 Cells ◽  
Cell Apoptosis ◽  
Active Component ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
B Cell Lymphoma ◽  
Oxygen Species ◽  
Protein Levels ◽  
Crataegus Pinnatifida

The neuroprotective mechanisms of Crataegus pinnatifida extracts and crataegolic acid were studied using paraquat induced cytotoxicity in PC12 cells. C. pinnatifida extracts were prepared using hexane, ethyl acetate, and 95% ethanol. Additionally, crataegolic acid (also known as maslinic acid) was found in C. pinnatifida extracts. Assessment methods included the examinations of cytotoxicity, intracellular reactive oxygen species and calcium changes, activity of caspase-3 and α-synuclein, apoptotic cell death, and the expression levels of the B-cell lymphoma 2 (Bcl-2) and BCL2-associated X (Bax) proteins to investigate the neuroprotective mechanisms of C. pinnatifida extracts and its active component, crataegolic acid. The three extracts and crataegolic acid exhibited potent neuroprotective actions against paraquat induced PC12 cell apoptosis at 5–20µg/mL and 80–100µM concentrations, respectively. The key protective mechanisms included decreasing cell apoptosis, upregulating Bcl-2 protein levels, and downregulating Bax protein levels. The 95% ethanol extract also decreased paraquat induced reactive oxygen species production, calcium overloading, and caspase-3 and α-synuclein activities. The beneficial effects of these extracts could be explained by the active component, crataegolic acid that also inhibited paraquat-induced apoptosis through the suppression of reactive oxygen species generation and the caspase-3 signaling pathway.

Toxicity assessment of metallic nickel nanoparticles in various biological models: An interplay of reactive oxygen species, oxidative stress, and apoptosis

2021 ◽  
pp. 074823372110110
Author(s):  
Shabnoor Iqbal ◽  
Farhat Jabeen ◽  
Abdul Shakoor Chaudhry ◽  
Muhammad Ajmal Shah ◽  
Gaber El-Saber Batiha
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Nickel Nanoparticles ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Volume Ratio ◽  
Nuclear Factor Κb ◽  
Metallic Nickel ◽  
Oxygen Species

Nickel nanoparticles (Ni-NPs) are widely used for multiple purposes in industries. Ni-NPs exposure is detrimental to ecosystems owing to widespread use, and so their toxicity is important to consider for real-world applications. This review mainly focuses on the notable pathophysiological activities of Ni-NPs in various research models. Ni-NPs are stated to be more toxic than bulk forms because of their larger surface area to volume ratio and are reported to provoke toxicity through reactive oxygen species generation, which leads to the upregulation of nuclear factor-κB and promotes further signaling cascades. Ni-NPs may contribute to provoking oxidative stress and apoptosis. Hypoxia-inducible factor 1α and mitogen-activated protein kinases pathways are involved in Ni-NPs associated toxicity. Ni-NPs trigger the transcription factors p-p38, p-JNK, p-ERK1/2, interleukin (IL)-3, TNF-α, IL-13, Fas, Cyt c, Bax, Bid protein, caspase-3, caspase-8, and caspase-9. Moreover, Ni-NPs have an occupational vulnerability and were reported to induce lung-related disorders owing to inhalation. Ni-NPs may cause serious effects on reproduction as Ni-NPs induced deleterious effects on reproductive cells (sperm and eggs) in animal models and provoked hormonal alteration. However, recent studies have provided limited knowledge regarding the important checkpoints of signaling pathways and less focused on the toxic limitation of Ni-NPs in humans, which therefore needs to be further investigated.

scholarly journals PAC1 regulates receptor tyrosine kinase transactivation in a reactive oxygen species-dependent manner

Peptides ◽  
2019 ◽  
Vol 120 ◽  
pp. 170017
Author(s):  
Terry W. Moody ◽  
Lingaku Lee ◽  
Tatiana Iordanskaia ◽  
Irene Ramos-Alvarez ◽  
Paola Moreno ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Oxygen Species
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