scholarly journals NaHS or Lovastatin Attenuates Cyclosporine A–Induced Hypertension in Rats by Inhibiting Epithelial Sodium Channels

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiu-Shi Wang ◽  
Chen Liang ◽  
Shuai Jiang ◽  
Di Zhu ◽  
Yu Sun ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Reactive Oxygen Species ◽  
Cyclosporine A ◽  
Reactive Oxygen ◽  
Kidney Cortex ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Open Probability ◽  
Induced Hypertension ◽  
Intracellular Cholesterol

The use of cyclosporine A (CsA) in transplant recipients is limited due to its side effects of causing severe hypertension. We have previously shown that CsA increases the activity of the epithelial sodium channel (ENaC) in cultured distal nephron cells. However, it remains unknown whether ENaC mediates CsA-induced hypertension and how we could prevent hypertension. Our data show that the open probability of ENaC in principal cells of split-open cortical collecting ducts was significantly increased after treatment of rats with CsA; the increase was attenuated by lovastatin. Moreover, CsA also elevated the levels of intracellular cholesterol (Cho), intracellular reactive oxygen species (ROS) via activation of NADPH oxidase p47phox, serum- and glucocorticoid-induced kinase isoform 1 (Sgk1), and phosphorylated neural precursor cell–expressed developmentally downregulated protein 4–2 (p-Nedd4-2) in the kidney cortex. Lovastatin also abolished CsA-induced elevation of α-, ß-, and γ-ENaC expressions. CsA elevated systolic blood pressure in rats; the elevation was completely reversed by lovastatin (an inhibitor of cholesterol synthesis), NaHS (a donor of H2S which ameliorated CsA-induced elevation of reactive oxygen species), or amiloride (a potent ENaC blocker). These results suggest that CsA elevates blood pressure by increasing ENaC activity via a signaling cascade associated with elevation of intracellular ROS, activation of Sgk1, and inactivation of Nedd4-2 in an intracellular cholesterol-dependent manner. Our data also show that NaHS ameliorates CsA-induced hypertension by inhibition of oxidative stress.

scholarly journals Reactive oxygen species contribute to sleep apnea-induced hypertension in rats

2007 ◽  
Vol 293 (5) ◽  
pp. H2971-H2976 ◽  
Author(s):  
Carmen M. Troncoso Brindeiro ◽  
Ana Q. da Silva ◽  
Kyan J. Allahdadi ◽  
Victoria Youngblood ◽  
Nancy L. Kanagy
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Reactive Oxygen Species ◽  
Sleep Apnea ◽  
Arterial Pressure ◽  
Reactive Oxygen ◽  
Mesenteric Arteries ◽  
Plain Water ◽  
Oxygen Species ◽  
Induced Hypertension

In clinical studies, sleep apnea is associated with hypertension, oxidative stress, and increased circulating endothelin-1 (ET-1). We previously developed a model of sleep apnea by exposing rats to eucapnic intermittent hypoxia (IH-C) during sleep, which increases both blood pressure and plasma levels of ET-1. Because similar protocols in mice increase tissue and plasma markers of oxidative stress, we hypothesized that IH-C generation of reactive oxygen species (ROS) contributes to the development of ET-1-dependent hypertension in IH-C rats. To test this, male Sprague-Dawley rats were instrumented with indwelling blood pressure telemeters and drank either plain water or water containing the superoxide dismutase mimetic, Tempol (4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl, 1 mM). Mean arterial pressure (MAP) and heart rate (HR) were recorded for 3 control days and 14 treatment days with rats exposed 7 h/day to IH-C or air/air cycling (Sham). On day 14, MAP in IH-C rats treated with Tempol (107 ± 2.29 mmHg) was significantly lower than in untreated IH-C rats (118 ± 9 mmHg, P < 0.05). Tempol did not affect blood pressure in sham-operated rats (Tempol = 101 ± 3, water = 101 ± 2 mmHg). Immunoreactive ET-1 was greater in plasma from IH-C rats compared with plasma from sham-operated rats but was not different from Sham in Tempol-treated IH-C rats. Small mesenteric arteries from IH-C rats but not Tempol-treated IH-C rats had increased superoxide levels as measured by ferric cytochrome c reduction, lucigenin signaling, and dihydroethidium fluorescence. The data show that IH-C increases ET-1 production and vascular ROS levels and that scavenging superoxide prevents both. Thus oxidative stress appears to contribute to increases in ET-1 production and elevated arterial pressure in this rat model of sleep apnea-induced hypertension.

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

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 Ethyl Rosmarinate Protects High Glucose-Induced Injury in Human Endothelial Cells

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3372 ◽  
Author(s):  
Yan-Hui Shen ◽  
Li-Ying Wang ◽  
Bao-Bao Zhang ◽  
Qi-Ming Hu ◽  
Pu Wang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Protective Effect ◽  
High Glucose ◽  
Reactive Oxygen ◽  
Annexin V ◽  
Ros Generation ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Jnk Pathway

Ethyl rosmarinate (RAE) is one of the active constituents from Clinopodium chinense (Benth.) O. Kuntze, which is used for diabetic treatment in Chinese folk medicine. In this study, we investigated the protective effect of RAE on high glucose-induced injury in endothelial cells and explored its underlying mechanisms. Our results showed that both RAE and rosmarinic acid (RA) increased cell viability, decreased the production of reactive oxygen species (ROS), and attenuated high glucose-induced endothelial cells apoptosis in a dose-dependent manner, as evidenced by Hochest staining, Annexin V–FITC/PI double staining, and caspase-3 activity. RAE and RA both elevated Bcl-2 expression and reduced Bax expression, according to Western blot. We also found that LY294002 (phosphatidylinositol 3-kinase, or PI3K inhibitor) weakened the protective effect of RAE. In addition, PDTC (nuclear factor-κB, or NF-κB inhibitor) and SP600125 (c-Jun N-terminal kinase, or JNK inhibitor) could inhibit the apoptosis in endothelial cells caused by high glucose. Further, we demonstrated that RAE activated Akt, and the molecular docking analysis predicted that RAE showed more affinity with Akt than RA. Moreover, we found that RAE inhibited the activation of NF-κB and JNK. These results suggested that RAE protected endothelial cells from high glucose-induced apoptosis by alleviating reactive oxygen species (ROS) generation, and regulating the PI3K/Akt/Bcl-2 pathway, the NF-κB pathway, and the JNK pathway. In general, RAE showed greater potency than RA equivalent.

scholarly journals Drosophila hemocytes recognize lymph gland tumors of mxc mutants and activate the Toll pathway in reactive oxygen species-dependent manner

2021 ◽  
Author(s):  
Suzuko Kinoshita ◽  
Kazuki Takarada ◽  
Yoshihiro H. Inoue
Keyword(s):  
Reactive Oxygen Species ◽  
Fat Body ◽  
Ectopic Expression ◽  
Reactive Oxygen ◽  
Underlying Mechanism ◽  
Innate Immune ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Matrix Metalloproteinase 1 ◽  
Membrane Components

Mechanisms of cancer cell recognition and elimination by the innate immune system remains unclear. Circulating hemocytes are associated with the hematopoietic tumors in Drosophila mxcmbn1 mutant larvae. The innate immune signalling pathways are activated in the fat body to suppress the tumor growth by inducing antimicrobial peptides (AMP). Here, we investigated the regulatory mechanism underlying the activation in the mutant. Reactive oxygen species accumulated in the hemocytes due to induction of dual oxidase and its activator. The hemocytes were also localized on the fat body. These were essential for transmitting the information on tumors toward the fat body to induce AMP expression. Regarding to the tumor recognition, we found that matrix metalloproteinase 1 (MMP1) and MMP2 were highly expressed in the tumors. Ectopic expression of MMP2 was associated with AMP induction in the mutants. Furthermore, the basement membrane components in the tumors were reduced and ultimately lost. The hemocytes may recognize the disassembly in the tumors. Our findings highlight the underlying mechanism via which macrophage-like hemocytes recognize tumor cells and relay the information toward the fat body to induce AMPs. and contribute to uncover the immune system's roles against cancer.

The molecular mechanisms of Phytophthora infestans in response to reactive oxygen species (ROS) stress

2021 ◽  
Author(s):  
Xiumei Luo ◽  
Tingting Tian ◽  
Maxime Bonnave ◽  
Xue Tan ◽  
Xiaoqing Huang ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Late Blight ◽  
Phytophthora Infestans ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Microbial Pathogens ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Tor Signaling ◽  
Potato Resistance

Reactive oxygen species (ROS) are critical for the growth, development, proliferation, and pathogenicity of microbial pathogens; however, excessive levels of ROS are toxic. Little is known regarding the signaling cascades in response to ROS stress in oomycetes such as Phytophthora infestans, the causal agent of potato late blight. Here, P. infestans was used as a model system to investigate the mechanism underlying the response to ROS stress in oomycete pathogens. Results showed severe defects in sporangium germination, mycelial growth, appressorium formation, and virulence of P. infestans in response to H2O2 stress. Importantly, these phenotypes mimic those of P. infestans treated with rapamycin, the inhibitor of target of rapamycin (TOR, 1-phosphatidylinositol-3-kinase). Strong synergism occurred when P. infestans was treated with a combination of H2O2 and rapamycin, suggesting that a crosstalk exists between ROS stress and the TOR signaling pathway. Comprehensive analysis of transcriptome, proteome and phosphorylation omics showed that H2O2 stress significantly induced the operation of the TOR-mediated autophagy pathway. Monodansylcadaverine (MDC) staining showed that in the presence of H2O2 and rapamycin, the autophagosome level increased in a dosage-dependent manner. Furthermore, transgenic potatoes containing double-stranded RNA of PiTOR (TOR in P. infestans) displayed high resistance to P. infestans. Taken together, TOR is involved in the ROS response and is a potential target for control of oomycete diseases, as host-mediated silencing of PiTOR enhances potato resistance to late blight.

scholarly journals Erigeron annuus (L.) Pers. Extract Inhibits Reactive Oxygen Species (ROS) Production and Fat Accumulation in 3T3-L1 Cells by Activating an AMP-Dependent Kinase Signaling Pathway

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 139 ◽  
Author(s):  
Yoon-Hee Choi ◽  
Ok-Hwan Lee ◽  
Yulong Zheng ◽  
Il-Jun Kang
Keyword(s):  
Reactive Oxygen Species ◽  
Signaling Pathway ◽  
Water Extract ◽  
Reactive Oxygen ◽  
Dependent Manner ◽  
Ros Production ◽  
Oxygen Species ◽  
Fat Accumulation ◽  
Ampk Signaling ◽  
Erigeron Annuus

Obesity is one of the major public health problems in the world because it is implicated in metabolic syndromes, such as type 2 diabetes, hypertension, and cardiovascular diseases. The objective of this study was to investigate whether Erigeron annuus (L.) Pers. (EAP) extract suppresses reactive oxygen species (ROS) production and fat accumulation in 3T3-L1 cells by activating an AMP-dependent kinase (AMPK) signaling pathway. Our results showed that EAP water extract significantly inhibits ROS production, adipogenesis, and lipogenesis during differentiation of 3T3-L1 preadipocytes. In addition, EAP decreased mRNA and protein levels of proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα). Moreover, EAP suppressed mRNA expressions of fatty acid synthase (FAS), lipoprotein lipase (LPL), adipocyte protein 2 (aP2) in a dose-dependent manner. Whereas, EAP upregulated adiponectin expression, phosphorylation levels of AMPK and carnitine palmitoyltransferase 1 (CPT-1) protein level during differentiation of 3T3-L1 preadipocytes. These results suggest that EAP water extract can exert ROS-linked anti-obesity effect through the mechanism that might involve inhibition of ROS production, adipogenesis and lipogenesis via an activating AMPK signaling pathway.

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