Precipitants of hepatic encephalopathy induce rapid astrocyte swelling in an oxidative stress dependent manner

2013 ◽  
Vol 536 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Vera Lachmann ◽  
Boris Görg ◽  
Hans Jürgen Bidmon ◽  
Verena Keitel ◽  
Dieter Häussinger
Keyword(s):  
Oxidative Stress ◽  
Hepatic Encephalopathy ◽  
Dependent Manner ◽  
Astrocyte Swelling ◽  
Stress Dependent

scholarly journals Oxidative stress increases megalin expression in the renal proximal tubules during the normoalbuminuric stage of diabetes mellitus

2018 ◽  
Vol 314 (3) ◽  
pp. F462-F470 ◽  
Author(s):  
Yoshifumi Kurosaki ◽  
Akemi Imoto ◽  
Fumitaka Kawakami ◽  
Masanori Yokoba ◽  
Tsuneo Takenaka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Hydrogen Peroxide ◽  
High Glucose ◽  
Renal Cortex ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphorylated Akt ◽  
Stress Dependent ◽  
Phosphatidylinositol 3

Megalin, an endocytic receptor expressed in proximal tubule cells, plays a critical role in renal tubular protein reabsorption and is associated with the albuminuria observed in diabetic nephropathy. We have previously reported increased oxidant production in the renal cortex during the normoalbuminuric stage of diabetes mellitus (DM); however, the relationship between oxidative stress and renal megalin expression during the normoalbuminuric stage of DM remains unclear. In the present study, we evaluated whether oxidative stress affects megalin expression in the normoalbuminuric stage of DM in a streptozotocin-induced diabetic rat model and in immortalized human proximal tubular cells (HK-2). We demonstrated that increased expression of renal megalin accompanies oxidative stress during the early stage of DM, before albuminuria development. Telmisartan treatment prevented the diabetes-induced elevation in megalin level, possibly through an oxidative stress-dependent mechanism. In HK-2 cells, hydrogen peroxide significantly increased megalin levels in a dose- and time-dependent manner; however, the elevation in megalin expression was decreased following prolonged exposure to severe oxidative stress induced by 0.4 mmol/l hydrogen peroxide. High-glucose treatment also significantly increased megalin expression in HK-2 cells. Concurrent administration of the antioxidant N-acetyl-cysteine blocked the effects of high glucose on megalin expression. Furthermore, the hydrogen peroxide-induced increase in megalin expression was blocked by treatment with phosphatidylinositol 3-kinase and Akt inhibitors. Increase of phosphorylated Akt expression was also seen in the renal cortex of diabetic rats. Taken together, our results indicate that mild oxidative stress increases renal megalin expression through the phosphatidylinositol 3-kinase-Akt pathway in the normoalbuminuric stage of DM.

scholarly journals Empagliflozin improves endothelial and cardiomyocyte function in human heart failure with preserved ejection fraction via reduced pro-inflammatory-oxidative pathways and protein kinase Gα oxidation

2020 ◽  
Author(s):  
Detmar Kolijn ◽  
Steffen Pabel ◽  
Yanna Tian ◽  
Mária Lódi ◽  
Melissa Herwig ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Linear Regression Analysis ◽  
Lipid Peroxide ◽  
Dependent Manner ◽  
Preserved Ejection Fraction ◽  
Human Heart Failure ◽  
Stress Dependent

Abstract Aims Sodium-glucose-cotransporter-2 inhibitors showed favourable cardiovascular outcomes, but the underlying mechanisms are still elusive. This study investigated the mechanisms of empagliflozin in human and murine heart failure with preserved ejection fraction (HFpEF). Methods and results The acute mechanisms of empagliflozin were investigated in human myocardium from patients with HFpEF and murine ZDF obese rats, which were treated in vivo. As shown with immunoblots and ELISA, empagliflozin significantly suppressed increased levels of ICAM-1, VCAM-1, TNF-α, and IL-6 in human and murine HFpEF myocardium and attenuated pathological oxidative parameters (H2O2, 3-nitrotyrosine, GSH, lipid peroxide) in both cardiomyocyte cytosol and mitochondria in addition to improved endothelial vasorelaxation. In HFpEF, we found higher oxidative stress-dependent activation of eNOS leading to PKGIα oxidation. Interestingly, immunofluorescence imaging and electron microscopy revealed that oxidized PKG1α in HFpEF appeared as dimers/polymers localized to the outer-membrane of the cardiomyocyte. Empagliflozin reduced oxidative stress/eNOS-dependent PKGIα oxidation and polymerization resulting in a higher fraction of PKGIα monomers, which translocated back to the cytosol. Consequently, diminished NO levels, sGC activity, cGMP concentration, and PKGIα activity in HFpEF increased upon empagliflozin leading to improved phosphorylation of myofilament proteins. In skinned HFpEF cardiomyocytes, empagliflozin improved cardiomyocyte stiffness in an anti-oxidative/PKGIα-dependent manner. Monovariate linear regression analysis confirmed the correlation of oxidative stress and PKGIα polymerization with increased cardiomyocyte stiffness and diastolic dysfunction of the HFpEF patients. Conclusion Empagliflozin reduces inflammatory and oxidative stress in HFpEF and thereby improves the NO–sGC–cGMP–cascade and PKGIα activity via reduced PKGIα oxidation and polymerization leading to less pathological cardiomyocyte stiffness.

scholarly journals Tumor-associated macrophages favor C26 murine colon carcinoma cell proliferation in an oxidative stress-dependent manner

2017 ◽  
Vol 37 (4) ◽  
pp. 2472-2480 ◽  
Author(s):  
Lavinia Luput ◽  
Emilia Licarete ◽  
Alina Sesarman ◽  
Laura Patras ◽  
Marius Costel Alupei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Colon Carcinoma ◽  
Carcinoma Cell ◽  
Dependent Manner ◽  
Tumor Associated Macrophages ◽  
Murine Colon Carcinoma ◽  
Stress Dependent ◽  
Murine Colon

scholarly journals Sporadic activation of an oxidative stress–dependent NRF2-p53 signaling network in breast epithelial spheroids and premalignancies

2020 ◽  
Vol 13 (627) ◽  
pp. eaba4200 ◽  
Author(s):  
Elizabeth J. Pereira ◽  
Joseph S. Burns ◽  
Christina Y. Lee ◽  
Taylor Marohl ◽  
Delia Calderon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Epithelial Cells ◽  
Stress Tolerance ◽  
Cell Lines ◽  
Epithelial Tissue ◽  
Dependent Manner ◽  
P53 Signaling ◽  
Breast Epithelial ◽  
Stress Dependent

Breast and mammary epithelial cells experience different local environments during tissue development and tumorigenesis. Microenvironmental heterogeneity gives rise to distinct cell regulatory states whose identity and importance are just beginning to be appreciated. Cellular states diversify when clonal three-dimensional (3D) spheroids are cultured in basement membrane, and one such state is associated with stress tolerance and poor response to anticancer therapeutics. Here, we found that this state was jointly coordinated by the NRF2 and p53 pathways, which were costabilized by spontaneous oxidative stress within 3D cultures. Inhibition of NRF2 or p53 individually disrupted some of the transcripts defining the regulatory state but did not yield a notable phenotype in nontransformed breast epithelial cells. In contrast, combined perturbation prevented 3D growth in an oxidative stress–dependent manner. By integrating systems models of NRF2 and p53 signaling in a single oxidative stress network, we recapitulated these observations and made predictions about oxidative stress profiles during 3D growth. NRF2 and p53 signaling were similarly coordinated in normal breast epithelial tissue and hormone-negative ductal carcinoma in situ lesions but were uncoupled in triple-negative breast cancer (TNBC), a subtype in which p53 is usually mutated. Using the integrated model, we correlated the extent of this uncoupling in TNBC cell lines with the importance of NRF2 in the 3D growth of these cell lines and their predicted handling of oxidative stress. Our results point to an oxidative stress tolerance network that is important for single cells during glandular development and the early stages of breast cancer.

GCDCA down-regulates gene expression by increasing Sp1 binding to the NOS-3 promoter in an oxidative stress dependent manner

2015 ◽  
Vol 96 (1) ◽  
pp. 39-51 ◽  
Author(s):  
Sandra González-Rubio ◽  
Laura López-Sánchez ◽  
Juan Muñoz-Castañeda ◽  
Clara I. Linares ◽  
Patricia Aguilar-Melero ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Dependent Manner ◽  
Stress Dependent

scholarly journals Withaferin A Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1063
Author(s):  
Tsu-Ming Chien ◽  
Kuang-Han Wu ◽  
Ya-Ting Chuang ◽  
Yun-Chiao Yeh ◽  
Hui-Ru Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Withaferin A ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
Dna Damages ◽  
Bladder Cancer Cells ◽  
Stress Dependent

Withaferin A (WFA), the Indian ginseng bioactive compound, exhibits an antiproliferation effect on several kinds of cancer, but it was rarely reported in bladder cancer cells. This study aims to assess the anticancer effect and mechanism of WFA in bladder cancer cells. WFA shows antiproliferation to bladder cancer J82 cells based on the finding of the MTS assay. WFA disturbs cell cycle progression associated with subG1 accumulation in J82 cells. Furthermore, WFA triggers apoptosis as determined by flow cytometry assays using annexin V/7-aminoactinomycin D and pancaspase detection. Western blotting also supports WFA-induced apoptosis by increasing cleavage of caspases 3, 8, and 9 and poly ADP-ribose polymerase. Mechanistically, WFA triggers oxidative stress-association changes, such as the generation of reactive oxygen species and mitochondrial superoxide and diminishment of the mitochondrial membrane potential, in J82 cells. In response to oxidative stresses, mRNA for antioxidant signaling, such as nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), superoxide dismutase 1 (SOD1), thioredoxin (TXN), glutathione-disulfide reductase (GSR), quinone dehydrogenase 1 (NQO1), and heme oxygenase 1 (HMOX1), are overexpressed in J82 cells. In addition, WFA causes DNA strand breaks and oxidative DNA damages. Moreover, the ROS scavenger N-acetylcysteine reverts all tested WFA-modulating effects. In conclusion, WFA possesses anti-bladder cancer effects by inducing antiproliferation, apoptosis, and DNA damage in an oxidative stress-dependent manner.

scholarly journals Stress Alters Rates and Types of Loss of Heterozygosity in Candida albicans

mBio ◽  
2011 ◽  
Vol 2 (4) ◽  
Author(s):  
A. Forche ◽  
D. Abbey ◽  
T. Pisithkul ◽  
M. A. Weinzierl ◽  
T. Ringstrom ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Genetic Diversity ◽  
Candida Albicans ◽  
Loss Of Heterozygosity ◽  
Mitotic Recombination ◽  
Stress Conditions ◽  
Dependent Manner ◽  
Content Type ◽  
Different Types ◽  
Stress Dependent

ABSTRACTGenetic diversity is often generated during adaptation to stress, and in eukaryotes some of this diversity is thought to arise via recombination and reassortment of alleles during meiosis.Candida albicans, the most prevalent pathogen of humans, has no known meiotic cycle, and yet it is a heterozygous diploid that undergoes mitotic recombination during somatic growth. It has been shown that clinical isolates as well as strains passaged once through a mammalian host undergo increased levels of recombination. Here, we tested the hypothesis that stress conditions increase rates of mitotic recombination inC. albicans, which is measured as loss of heterozygosity (LOH) at specific loci. We show that LOH rates are elevated duringin vitroexposure to oxidative stress, heat stress, and antifungal drugs. In addition, an increase in stress severity correlated well with increased LOH rates. LOH events can arise through local recombination, through homozygosis of longer tracts of chromosome arms, or by whole-chromosome homozygosis. Chromosome arm homozygosis was most prevalent in cultures grown under conventional lab conditions. Importantly, exposure to different stress conditions affected the levels of different types of LOH events, with oxidative stress causing increased recombination, while fluconazole and high temperature caused increases in events involving whole chromosomes. Thus,C. albicansgenerates increased amounts and different types of genetic diversity in response to a range of stress conditions, a process that we term “stress-induced LOH” that arises either by elevating rates of recombination and/or by increasing rates of chromosome missegregation.IMPORTANCEStress-induced mutagenesis fuels the evolution of bacterial pathogens and is mainly driven by genetic changes via mitotic recombination. Little is known about this process in other organisms.Candida albicans, an opportunistic fungal pathogen, causes infections that require adaptation to different host environmental niches. We measured the rates of LOH and the types of LOH events that appeared in the absence and in the presence of physiologically relevant stresses and found that stress causes a significant increase in the rates of LOH and that this increase is proportional to the degree of stress. Furthermore, the types of LOH events that arose differed in a stress-dependent manner, indicating that eukaryotic cells generate increased genetic diversity in response to a range of stress conditions. We propose that this “stress-induced LOH” facilitates the rapid adaptation ofC. albicans, which does not undergo meiosis, to changing environments within the host.

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